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["Journal of Investigative Psychology and Offender Profiling, EarlyView. ", "\nAbstract\nWe reviewed the child and the adult literature on the impact of witnesses drawing what happened on the number of details recalled and the accuracy of the reported details. Most experiments reported a beneficial effect of drawing what happened (or drawing the scene) on the number of details reported primarily in free recall and sometimes also in cued recall. The consensus across studies was that drawing protocols did not negatively impact the accuracy of reported details (when accuracy was attainable) unless suggestive details were drawn. These results were largely consistent regardless of interviewer expertise or protocol used. Draw‐and‐tell instructions should be considered by forensic investigators for the following reasons: (1) the beneficial effect on number of details recalled with no detriment to accuracy, (2) the added benefit for children who need additional interviewer support, and (3) the ease at which the instruction can be implemented with minimal expertise or training. However, more ecologically valid research is needed to establish the efficacy of drawing (1) in forensic interviews, (2) in the presence of misinformation, (3) across instances of repeated event memory, and (4) across sequential interviews.\n"]

["Journal of Investigative Psychology and Offender Profiling, EarlyView. ", "\nAbstract\nThe aim of the study was to investigate the offence characteristics and motivations for revenge filicides. Revenge filicide is an act where one parent kills their own offspring for retribution to hurt and upset the other parent. The cases of 20 revenge filicide murderers (14 male and six female) were analysed to determine the motivations and offence characteristics of revenge filicide offenders. It is the first South African study to highlight the motivations and associated characteristics in revenge filicides. Themes such as a loss of social identity due to rejection; extreme rage type anger; external locus of control; sadism; a desire to cause pain and a need to inflict harm are highlighted in this article. The initial emotional response may escalate from mild anger to a level of narcissistic rage which eventually culminates in the murdering of the child to punish and hurt the other parent and to restore control.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 19, Issue 3, Page 248-260, October 2022. ", "\nAbstract\nThe purpose of this research is to further understanding of how environmental factors impact on the distance an offender travels from their home to their crime scene ‐ the so called ‘journey‐to‐crime’ (JTC.). Currently, Geographic Profilers rely on relatively generic JTC research to form inferences about the likely distance travelled by an offender, and may be missing the opportunity to make a more bespoke assessment which takes these factors into account. 1186 cases of female stranger sexual assault (Study 1) and 124 cases of stranger homicide (Study 2) were analysed. Euclidean measurement of distance was provided from the offender's recorded home to 3 crime site locations: (1) the initial contact with victim, (2) the assault/murder, and (3) the victim release/body disposal. Each crime site location was coded according to: (a) population density and (b) urban or rural. Initial analysis examined the median distance travelled from an offender's residence to the three different crime site locations. Significant findings for stranger sexual assaults indicated that the initial contact location was significantly further from an offender's residence compared to the sexual assault and victim release location. This was not replicated for stranger homicide offences. Both sexual assault and homicide cases revealed that the distance travelled to the ‘initial approach’ location did not differ according to population density, or whether the location was urban or rural. Regarding ‘sexual assault’ locations, offenders were found to travel significantly further from their home to attack their victim in low population density and rural areas. Results showed that both sexual assault and homicide offenders travelled significantly further from their home to the ‘victim release/body disposal’ site in low population density areas and rural areas. These findings have important, practical applications for investigations, allowing Geographic Profilers to provide more bespoke inferences about an offender's journey to crime.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 19, Issue 3, Page 221-230, October 2022. ", "\nAbstract\nWhilst crime scene staging in homicide, as an attempt to avoid detection, has attracted some scholarly attention in recent years, staging a body disposal site has not been similarly scrutinised. Indeed, whilst some statistical studies note moving a homicide victim's body as a distinct crime scene behaviour, there is little discussion or analysis of body disposal sites generally. This case seeks to illustrate how a body disposal site may be staged—in three different forms—and to supplement existing quantitative data on offender behaviours undertaken to avoid detection. In so doing, a new category of staging is proposed: staging a body disposal site.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 19, Issue 3, Page 204-220, October 2022. ", "\nAbstract\nAs immigration and homeland security become of greater concern both at a global and national level, it is imperative to review existing research on observers' ability to accurately detect deception in non‐native speakers. Objectives of this systematic review were to summarise the evidence on adult observers' ability to accurately detect deception in non‐native speakers compared to native speakers; identify response biases in observers' judgements when judging native versus non‐native speakers' statements; and explore whether differences in observers' deception detection accuracy varies across targets' proficiency levels. Two reviewers independently searched five databases and screened for all quantitative studies that met pre‐selected search criteria. Out of 1885 records identified through database searching, 11 studies met the inclusion criteria. Discriminability for non‐native speakers was above chance in four samples. Most studies found support for a lie bias when judging non‐native speakers and a truth bias when judging native speakers. In addition to further research, these results highlight the need for better reporting of stimuli and observer samples as well as a standardised measure of individuals' proficiency level.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 19, Issue 3, Page 135-150, October 2022. ", "\nAbstract\nRape offences in England and Wales garner incredibly low levels of convictions. The policing stage of a complaint experiences high levels of case discontinuances. The aim of this research is to explore police officer's decision making in rape cases and how that shapes the attrition of cases. The method employed in this study is qualitative interviews, with retired or serving police officers, with the use of vignettes. This study found that police officers prioritise and continue with cases that they predict to be most likely to reach a conviction. Such predictions are guided by assessments over the strength of the evidence in cases, informed by a range of legal and extra‐legal factors. An overarching prediction employed is how likely a jury would be to convict a case. However, the participants reported that they find it incredibly difficult to accurately predict jury verdicts, making such decisions premised on a flawed logic.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 19, Issue 3, Page 118-134, October 2022. ", "\nAbstract\nThe purpose of this study is to explore cases of missing persons suspected of being criminal. Specifically, this research aims to empirically describe the circumstances surrounding criminal disappearances and examine whether there are different subcategories within these cases using a victimological framework. The data used in this study come from an operational police database. The sample includes 155 unsolved missing person cases whose thorough investigation by the police concluded that a criminal motive remained the most likely hypothesis. These cases occurred on the entire territory of metropolitan France and overseas. Multidimensional scale analysis was used to explore the context of disappearance according to missing person characteristics, lifestyle, everyday activities, and situational exposure at the time of the disappearance. Results show that the distribution of variables in a two‐dimensional space reveals four distinct different categories related to lifestyle and situational exposure: riskier lifestyle, riskier situation, safer situation, and safer lifestyle. This study is the first to empirically explore unsolved missing person cases suspected of a criminal outcome. Moreover, the framework used in this study demonstrates the importance of victimology in an investigative context.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 19, Issue 3, Page 231-247, October 2022. ", "\nAbstract\nVeracity judgements are important in legal and investigative contexts. However, people are poor judges of deception, often relying on incorrect behavioural cues when these may reflect the situation more than the sender's internal state. We investigated one such situational factor relevant to forensic contexts: handcuffing suspects. Judges—police officers (n = 23) and laypersons (n = 83)—assessed recordings of suspects, providing truthful and deceptive responses in an interrogation setting where half were handcuffed. Handcuffing was predicted to undermine efforts to judge veracity by constraining suspects' gesticulation and by priming stereotypes of criminality. It was found that both laypersons and police officers were worse at detecting deception when judging handcuffed suspects compared to non‐handcuffed suspects, while not affecting their judgement bias; police officers were also overconfident in their judgements. The findings suggest that handcuffing can negatively impact veracity judgements, highlighting the need for research on situational factors to better inform forensic practice.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 19, Issue 3, Page 261-278, October 2022. ", "\nAbstract\nAsking suspects for a free account (FA) at the start of an interview is considered good practice in a growing number of police organisations, whereas in others it still is not commonplace. This study explored whether interviews with or without such an invitation yielded more information from guilty suspects. Students in safety and security committed a mock crime and were then interviewed using a strategy of gradual disclosure of evidence, in the experimental condition preceded with an FA invitation (n = 20) and without such an invitation in the control condition (n = 17). On average, relatively little information was collected in the FA phase and far more in the subsequent gradual disclosure phase. However, the FA condition yielded seven confessions, four of which were given already in the FA phase. The No FA condition yielded only two confessions. Other differences in yield were not found. These findings indicate that an FA invitation could lead to some relevant and important information, such as a confession, being gathered already at an early stage of an interview, and that such an invitation does not hamper the gathering of further information later in the interview.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 19, Issue 3, Page 185-203, October 2022. ", "\nAbstract\nInvestigative interviewing can be a difficult task. Challenges may be exacerbated when interviewing English language learners. The field of eyewitness testimony lacks research on what troubles of understanding are generated by non‐native speakers and how these troubles are resolved. Thus, we undertook an exploratory study in which we aimed to provide definitions for identifying and characterising both troubles of understanding and resolutions. Data were simulated interviews between 17 dyads of native English‐speaking student‐interviewers and English language learner witnesses of a mock crime. We identified misunderstandings in each interaction and tracked who misunderstood, when the misunderstanding occurred (free/cued recall), whether it was resolved, and resolution strategies. We validated video analysis by checking for information consistency in the subsequent interviewer notes. Across dyads, 40 misunderstandings were found, with at least one in each interview. Witnesses misunderstood significantly more in the cued recall portion of the interview, while interviewers misunderstood more during free recall. Notably, participants resolved misunderstandings more often than not, used a variety of resolution strategies, and employed more strategies in unresolved instances. Interviewer notes confirmed our resolution analysis in 39/40 instances. The results suggest that the interviewers used creativity, flexibility, and a repertoire of different strategies when misunderstandings occurred.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 19, Issue 3, Page 167-184, October 2022. ", "\nAbstract\nThe current study aimed at testing the impact of the cognitive interview for suspects (CIS) used by trained custom officers on the quantity of gathered details, compared to a control standard interview (SI) used by untrained officers. Forty‐five mock‐suspects were required to perform a series of actions and each was interviewed by a pair of customs officers. Participants had to give statements containing truthful parts and deceptive parts. The CIS elicited significantly more details than the SI. Truthful parts of the statements contained more details than deceptive parts. An interaction effect revealed that the CIS elicited a higher number of action details in truthful parts. It is worthwhile for professionals in the field to adopt the CIS, which provides valuable benefits for information gathering. Moreover, the increase in action details raise the question of considering it as a possible lie detection tool.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 19, Issue 3, Page 103-117, October 2022. ", "\nAbstract\nThis study developed and tested a new geographic profiling method for automating suspect prioritisation in crime investigations. The Geographic Profiling Suspect Mapping And Ranking Technique (GP‐SMART) maps suspects' activity locations available in police records—such as home addresses, family members' home addresses, prior offence locations, locations of non‐crime incidents, and other contacts with police—and ranks suspects based on both the proximity and nature of these locations, relative to an input crime. In accuracy tests using solved burglary, robbery and extra‐familial sex offence cases in New Zealand (n = 4511), GP‐SMART ranked the offender at or near the top of the suspect list at rates greatly exceeding chance. Highlighting the benefit of its novel inclusion and differentiation of many different types of activity location, GP‐SMART also outperformed baseline methods—approximating existing algorithms—that ranked suspects using only the proximity of their activity locations, or home addresses, to the input crime.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 19, Issue 3, Page 151-166, October 2022. ", "\nAbstract\nAlthough building rapport before an investigative interview is recommended—and sometimes empirically beneficial—to eyewitness memory, no research has experimentally examined the effects of maintaining rapport during a witness interview on adult eyewitness recall. As a result, the present study assessed the impact of rapport on eyewitness recall accuracy by comparing a pre‐interview rapport only condition with a maintained rapport condition (where rapport was built before and maintained during the interview) and a no rapport control condition. Results revealed no benefits (or detriments) of building initial rapport—or any additional benefits of maintaining rapport—on witness recall quality, quantity, or ‘don't know’ responses. Our findings suggest that rapport or its maintenance may not directly affect eyewitness recall. However, as rapport is a humane eyewitness interviewing technique with some empirical support, we still advocate for its continued use.\n"]

["Journal of Investigative Psychology and Offender Profiling, EarlyView. ", "\nAbstract\nCurrent literature on ‘honour’‐based abuse (HBA) has largely focussed on exploring the lived experience of individuals, with limited analysis of the prevalence and associations of abuse characteristics. The aim of this study was to identify base rates of survivor, perpetrator and abuse characteristics. To identify these characteristics and their prevalence, 160 cases from Savera UK, a charity specialising in HBA and harmful practices, were coded for 66 variables and descriptive statistics produced. Fifteen of the coded abuse characteristics were present in more than 50% of cases, with ‘Emotional/psychological abuse and coercive control’, ‘Specific family cultural traditions’, ‘Gender‐based socialisation’ and ‘Physical violence’ being the only characteristics seen in more than 75% of cases. These represent the core characteristics of HBA but there are indications of qualitative and quantitate differences in this sample. Understanding the prevalence of characteristics is key to effectively identifying abuse, supporting survivors and improving effective prevention strategies.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 19, Issue 2, Page 73-87, June 2022. ", "\nAbstract\nFactors such as cultural norms and stereotypes influence how child sexual abuse (CSA) is perceived in relation to gender of the offender and perceptions of responsibility and harm in Puerto Rico. Finkelhor and Browne's traumagenic dynamics model served as the theoretical framework for the investigation because it addresses four key factors related to the experience of CSA victims. A total of 525 people living in Puerto Rico participated in the study. They were asked to read a hypothetical case of CSA by a teacher with a minor student and answer related questions. Point‐biserial correlational analyses were used to assess the influence of gender of the offender on perceptions of CSA. Results of the study indicated the male offender was attributed more responsibility and harm for the offence. Both male and female minor victims were identified by participants as partly responsible for the offence. Male and female offenders were identified as victims. Findings of this study could help to improve understanding of cultural differences in perceptions of CSA cases and its consequences.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 19, Issue 2, Page 88-99, June 2022. ", "\nAbstract\nThe need for remote psychological assessment came to the fore during the Covid‐19 pandemic lockdown. This paper examines the qualitative experiences of psychologists and patients using remote video interfaces for psychological assessment during that period. The aim was to gain qualitative data on the personal experiences of both parties and explore whether remote assessment via video interface is a satisfactory method for psychological evaluations. Patients were seen for psychological assessments by consultant Clinical and Counselling Psychologists via through videoconference. Consultants and patients were asked about their experience of the video assessment and the consultant recorded their responses. Content Analysis was used to analyse the responses. The remote mode of assessment was found to be satisfactory to both patient and psychologist, although technical issues were highlighted to be the most disruptive to assessments. Consultants reported a certain level of fatigue, particularly after evaluations, and some of them commented that they had to try harder than in a face‐to‐face evaluation. Distraction in the patient environment was considered detrimental. The small sample size which requires further replication studies. Overall, the use of videoconference was found to be a satisfactory method for psychological assessment with some areas for improvement, such as technical difficulties and fatigue.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 19, Issue 2, Page 58-72, June 2022. ", "\nAbstract\nExisting policing policy offers a rational approach to decision‐making with minimal reference to human judgement within child death investigations. This study adopted a mixed methodology to capture decisional processes of 26 serving detective inspectors and detective sergeants whilst responding to an immersive scenario which simulated the first hours of a Sudden and Unexpected Death in Children (SUDC) investigation. Participants were presented with four decision points, during which they were asked to choose from decision options while reflecting upon personal and situational factors influencing that decision. Thematic analysis of responses found that investigators disclosed ‘anxiety’ and ‘uncertainty’ throughout their decision‐making during the scenario. In addition, there was no evidence of investigators utilising the models formally advocated within policing literature to make their decisions and assessments. As a result, it is suggested that further improvements are made regarding investigative decision‐making models within operational policing where ‘anxiety’ and ‘uncertainty’ is heightened.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 19, Issue 2, Page 40-57, June 2022. ", "\nAbstract\nUntil recently, empirical evidence exploring Child Sexual Exploitation (CSE) has been scarce, particularly in relation to contact exploitation, where the convicted perpetrator seeks direct physical (offline) contact as opposed to solely targeting the victim online. This article presents a systematic review of the UK's contact CSE perpetrator literature, searching from 2009 to the present day to ensure that studies encompass the categorisations detailed within the CSE statutory definitions. Twenty‐three research articles were appraised using a Mixed Methods Appraisal Tool (MMAT). A narrative synthesis approach was used to synthesise the findings from qualitative and mixed methods studies identifying four significant analytical themes including (a) barriers to examining a complex phenomenon, (b) recognising the contact CSE perpetrator, (c) understanding the contact CSE perpetrator and (d) responding to the contact CSE perpetrator. This review synthesises evidence in a singular study, ideal for policy‐makers and stakeholders to provide a more comprehensive safeguarding response, guide future research directions, and provide suggestions for law enforcement disruption strategies within the United Kingdom. Recommendations for policy, practice, procedure and training include improving the recording of data, re‐categorising CSE as CSA, targeting harmful sexual behaviour and group offending, and designing evidenced based perpetrator treatment programmes. Future research centring on the perpetrator's adverse experiences and the strategies used to instigate sexual contact could advance understanding of how these crimes could be prevented.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 19, Issue 1, Page 20-32, January 2022. ", "\nAbstract\nPrevious literature suggests that covering of a homicide victim's face by an offender indicates a pre‐existing relationship. Operational definitions discriminate between three forms of victim covering (i) Masking (ii) Cloaking and (iii) Concealment. 126 UK homicide cases were examined to explore whether any evidence‐based investigative inferences could be supported in cases of victim covering viewed through an instrumental/expressive framework. No statistically significant differences were found between face covering behaviour and the relationship between victim and offender, previous convictions, and offender age, although there was a high frequency of elderly female victims of masking. The findings are discussed in relation to offender‐profiling.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 19, Issue 1, Page 3-19, January 2022. ", "\nAbstract\nThe aim of this study was to investigate the different types of resistant behavioural responses to unanswerable questions, their respective individual contribution to the overall variance in resistance efficacy, and their differential protective effect on repeated questioning, interrogative pressure, and delayed suggestibility. The participants were 360 children aged between 7 and 17 years, 180 of whom were suspected victims of sexual abuse and 180 matched peers for age, sex and IQ. All children completed the Gudjonsson Suggestibility Scale 2. Delayed suggestibility was measured after a 1‐week delay. The findings show that ‘don't know’, ‘direct explanation’, and ‘no’ answers are unrelated response styles that have individual effects on resistance to misleading questions. ‘Direct explanation’ answers are most stable and robust and increase incrementally with age in children, whilst ‘no’ answers decline. The findings suggest that ‘Don't know’, ‘direct explanation’, and ‘no’ answers are driven by different cognitive and social processes.\n"]

["Acta Physiologica, EarlyView. ", "\nAbstract\n\nAim\nDual Specificity Phosphatase 3 (DUSP3) regulates the innate immune response, with a putative role in angiogenesis. Modulating inflammation and perfusion contributes to renal conditioning against ischaemia/reperfusion (I/R). We postulate that the functional loss of DUSP3 is associated with kidney resistance to I/R.\n\n\nMethods\nTen C57BL/6 male WT and Dusp3−/− mice underwent right nephrectomy and left renal I/R (30 min/48 hours). Renal injury was assessed based on serum levels of urea (BUN) and Jablonski score. The expression of CD31 and VEGF vascular markers was quantified by RT‐qPCR and immuno‐staining. Renal resistivity index (RRI) was measured in vivo by Doppler ultrasound. Comparative phosphoproteomics was conducted using IMAC enrichment of phosphopeptides. Inflammatory markers were quantified at both mRNA and protein levels in ischaemic vs non‐ischaemic kidneys in WT vs Dusp3−/−.\n\n\nResults\nAt baseline, we located DUSP3 in renal glomeruli and endothelial cells. CD31‐positive vascular network was significantly larger in Dusp3−/− kidneys compared to WT, with a lower RRI in Dusp3−/− mice. Following I/R, BUN and Jablonski score were significantly lower in Dusp3−/− vs WT mice. Phosphoproteomics highlighted a down‐regulation of inflammatory pathways and up‐regulation of phospho‐sites involved in cell metabolism and VEGF‐related angiogenesis in Dusp3−/− vs WT ischaemic kidneys. Dusp3−/− ischaemic kidneys showed decreased mRNA levels of CD11b, TNF‐α, KIM‐1, IL‐6, IL‐1β and caspase‐3 compared to controls. The numbers of PCNA‐, F4‐80‐ and CD11b‐positive cells were reduced in Dusp3−/− vs WT kidneys post‐I/R.\n\n\nConclusion\nGenetic inactivation of Dusp3 is associated with kidney conditioning against I/R, possibly due to attenuated inflammation and improved perfusion.\n\n"]

["Acta Physiologica, EarlyView. ", "\nAbstract\n\nAims\nIt is unknown how β‐adrenergic stimulation affects calcium dynamics in individual RyR2 clusters and leads to the induction of spontaneous calcium waves. To address this, we analysed spontaneous calcium release events in green fluorescent protein (GFP)‐tagged RyR2 clusters.\n\n\nMethods\nCardiomyocytes from mice with GFP‐tagged RyR2 or human right atrial tissue were subjected to immunofluorescent labelling or confocal calcium imaging.\n\n\nResults\nSpontaneous calcium release from single RyR2 clusters induced 91.4% ± 2.0% of all calcium sparks while 8.0% ± 1.6% were caused by release from two neighbouring clusters. Sparks with two RyR2 clusters had 40% bigger amplitude, were 26% wider, and lasted 35% longer at half maximum. Consequently, the spark mass was larger in two‐ than one‐cluster sparks with a median and interquartile range for the cumulative distribution of 15.7 ± 20.1 vs 7.6 ± 5.7 a.u. (P < .01). β2‐adrenergic stimulation increased RyR2 phosphorylation at s2809 and s2815, tripled the fraction of two‐ and three‐cluster sparks, and significantly increased the spark mass. Interestingly, the amplitude and mass of the calcium released from a RyR2 cluster were proportional to the SR calcium load, but the firing rate was not. The spark mass was also higher in 33 patients with atrial fibrillation than in 36 without (22.9 ± 23.4 a.u. vs 10.7 ± 10.9; P = .015).\n\n\nConclusions\nMost sparks are caused by activation of a single RyR2 cluster at baseline while β‐adrenergic stimulation doubles the mass and the number of clusters per spark. This mimics the shift in the cumulative spark mass distribution observed in myocytes from patients with atrial fibrillation.\n\n"]

["Acta Physiologica, Volume 233, Issue 3, November 2021. ", "\nAbstract\n\nAim\nSubcellular fractionation is often used to determine the subcellular localization of proteins, including whether a protein translocates to the nucleus in response to a given stimulus. Examining nuclear proteins in skeletal muscle is difficult because myonuclear proteins are challenging to isolate unless harsh treatments are used. This study aimed to determine the most effective method for isolating and preserving proteins in their native state in skeletal muscle.\n\n\nMethods\nWe compared the ability of detergents, commercially available kit‐based and K+‐based physiological methodologies for isolating myonuclear proteins from resting samples of human muscle by determining the presence of marker proteins for each fraction by western blot analyses.\n\n\nResults\nWe found that following the initial pelleting of nuclei, treatment with 1% Triton‐X 100, 1% CHAPS or 0.5% Na‐deoxycholate under various ionic conditions resulted in the nuclear proteins being either resistant to isolation or the proteins present behaving aberrantly. The nuclear proteins in brain tissue were also resistant to 1% Triton‐X 100 isolation. Here, we demonstrate aberrant behaviour and erroneous localization of proteins using the kit‐based method. The aberrant behaviour was the activation of Ca2+‐dependent protease calpain‐3, and the erroneous localization was the presence of calpain‐3 and troponin I in the nuclear fraction.\n\n\nConclusion\nOur findings indicate that it may not be possible to reliably determine the translocation of proteins between subcellular locations and the nucleus using subcellular fractionation techniques. This study highlights the importance of validating subcellular fractionation methodologies using several subcellular‐specific markers and solutions that are physiologically relevant to the intracellular milieu.\n\n"]

["Acta Physiologica, Volume 233, Issue 3, November 2021. ", "\nAbstract\nChemically skinned fibres allow the study of human muscle contractile function in vitro. A particularly important parameter is specific force (SF), that is, maximal isometric force divided by cross‐sectional area, representing contractile quality. Although SF varies substantially between studies, the magnitude and cause of this variability remains puzzling. Here, we aimed to summarize and explore the cause of variability in SF between studies. A systematic search was conducted in Medline, Embase and Web of Science databases in June 2020, yielding 137 data sets from 61 publications which studied healthy, young adults. Five‐fold differences in mean SF data were observed. Adjustments to the reported data for key methodological differences allowed between‐study comparisons to be made. However, adjustment for fibre shape, swelling and sarcomere length failed to significantly reduce SF variance (I2 = 96%). Interestingly, grouping papers based on shared authorship did reveal consistency within research groups. In addition, lower SF was found to be associated with higher phosphocreatine concentrations in the fibre activating solution and with Triton X‐100 being used as a skinning agent. Although the analysis showed variance across the literature, the ratio of SF in single fibres containing myosin heavy chain isoforms IIA or I was found to be consistent across research groups. In conclusion, whilst the skinned fibre technique is reliable for studying in vitro force generation of single fibres, the composition of the solution used to activate fibres, which differs between research groups, is likely to heavily influence SF values.\n"]

["Acta Physiologica, Volume 233, Issue 3, November 2021. ", "\nAbstract\n\nAim\nThis study investigates the role of calcineurin for angiotensin II (AngII)‐induced vascular remodelling with the help of a mouse model lacking the catalytic beta subunit of calcineurin (PPP3CB KO).\n\n\nMethods\nWildtype (WT) and PPP3CB KO mice were treated for 4 weeks with AngII followed by assessment of blood pressure, histological evaluation of aortas and mRNA analysis of aortic genes PPP3CB‐dependently regulated by AngII. Primary murine vascular smooth muscle cells (VSMCs) were used for qPCR, ELISA and Western Blot experiments as well as wound healing and cell proliferation assays.\n\n\nResults\nUpon AngII treatment, PPP3CB KO mice showed less aortic media thickening, lumen dilation and systolic blood pressure compared to WT mice. Next‐generation sequencing data of aortic tissue indicated an increase in extracellular matrix components (EMCs), cell migration and cell proliferation. A PPP3CB‐dependent increase in EMC was confirmed by qPCR in aorta and VSMCs. PPP3CB‐dependent stimulation of VSMC migration could be verified by wound healing assays but markers of enhanced cell proliferation were only detectable in aortic tissue of WT mice but not in isolated WT or KO VSMCs. We could demonstrate in VSMCs with pharmacological inhibitors that PPP3CB leads to enhanced heparin‐binding EGF‐like growth factor (HB‐EGF) secretion, epidermal growth factor receptor (EGFR) activation and consecutive stimulation of transforming growth factor β(TGFβ) and connective tissue growth factor (CTGF) signalling that enhances collagen expression.\n\n\nConclusion\nAngII‐induced vascular remodelling involves PPP3CB, which leads to enhanced EMC production, VSMC migration and sustained increase in systolic blood pressure via HBEGF/EGFR‐TGFβ‐CTGF signalling.\n\n"]

["Acta Physiologica, EarlyView. ", "\nAbstract\n\nAim\nSlc26a9 is a member of the Slc26 multifunctional anion transporter family. Polymorphisms in Slc26a9 are associated with an increased incidence of meconium ileus and diabetes in cystic fibrosis patients. We investigated the expression of Slc26a9 in the murine pancreatic ducts, islets and parenchyma, and elucidated its role in pancreatic ductal electrolyte and fluid secretion and endocrine function.\n\n\nMethods\nPancreatic Slc26a9 and CFTR mRNA expression, fluid and bicarbonate secretion were assessed in slc26a9−/− mice and their age‐ and sex‐matched wild‐type (wt) littermates. Glucose and insulin tolerance tests were performed.\n\n\nResults\nCompared with stomach, the mRNA expression of Slc26a9 was low in pancreatic parenchyma, 20‐fold higher in microdissected pancreatic ducts than parenchyma, and very low in islets. CFTR mRNA was ~10 fold higher than Slc26a9 mRNA expression in each pancreatic cell type. Significantly reduced pancreatic fluid secretory rates and impaired glucose tolerance were observed in female slc26a9−/− mice, whereas alterations in male mice did not reach statistical significance. No significant difference was observed in peripheral insulin resistance in slc26a9−/− compared to sex‐ and aged‐matched wt controls. In contrast, isolated slc26a9−/− islets in short term culture displayed no difference in insulin content, but a significantly reduced glucose‐stimulated insulin secretion compared to age‐ and sex‐matched wt islets, suggesting that the impaired glucose tolerance in the absence of Slc26a9 expression these is a pancreatic defect.\n\n\nConclusions\nDeletion of Slc26a9 is associated with a reduction in pancreatic fluid secretion and impaired glucose tolerance in female mice. The results underline the importance of Slc26a9 in pancreatic physiology.\n\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 18, Issue 3, Page 185-200, October 2021. ", "\nSummary\nWhile earlier studies of investigative interviews with suspects have primarily been conducted within the context of police work, few have considered the interview practices with high‐status suspects in the financial area. This article aims to provide insight into distinctive features of interviewing these suspects. The study focuses on the impact various interviewing techniques can have on suspects’ disclosing information. To this end, 205 h of audio‐recorded actual interviews with 28 high‐status suspects were examined. Next to rapport building and confrontation, displaying authoritative behaviour can be considered a separate interviewing category. A positive correlation between rapport building and information disclosure was found. Finally, challenging the accounts of suspects results in more case‐related information than an authoritative approach.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 18, Issue 3, Page 157-169, October 2021. ", "\nAbstract\nCyber bullying (CB) might be relatively new in comparison to School‐Bullying (SB); nonetheless, both types have a negative impact on victims' psychological state. This project investigated CB in the UK and examined the victimisation means, as well as the reasons behind it. Four hundred and eight participants completed an online survey, which includes the 52‐item measure Cyber‐bullying and Online Aggression survey (CBOAS). The survey was advertised on social media and was active for nine months. From the sample, 37.26% reported that they had experienced CB victimisation more than once. Females seem to be more frequently involved in CB, particularly on Facebook and by spreading rumours. Such incidents usually result from arguments in real‐life settings. Many victims were able to stop their CB victimisation by standing up to their CB perpetrators. There are indications that CB functions as a subtype of SB. Implications and limitations are discussed in detail.\n"]

["Journal of Investigative Psychology and Offender Profiling, Volume 18, Issue 3, Page 170-184, October 2021. ", "\nAbstract\nThe data from the K‐12 School Shooting Database (K‐12 SSDB) of 1,544 school shootings were used to explore patterns of mass school shootings in the United States, with particular focus on the interplay between relevant predictors of these tragic events. Through a conjunctive analysis of case configurations (CACC), results from the current study show that (1) mass school shootings are rare and cluster significantly among dominant situational profiles, defined by the unique combination of variables attributes; (2) mass school shootings are never pre‐planned and in no case involve hostages. Current findings are discussed in light of existing school shooting scholarship and recommendations for policy and future areas of research are offered.\n"]

["Acta Physiologica, EarlyView. ", "\nAbstract\n\nAim\nArteriogenesis constitutes the most efficient endogenous rescue mechanism in cases of cerebral ischaemia. The aim of this work was to investigate whether angiotensin‐converting enzyme inhibitors (ACEi) stimulates, and angiotensin II receptor type 1 blockers (ARB) inhibits cerebral collateral growth by applying a three‐vessel occlusion (3‐VO) model in rat.\n\n\nMethods\nCerebral collateral growth was measured post 3‐VO (1) by assessing blood flow using the cerebrovascular reserve capacity (CVRC) technique, and (2) by assessing vessel diameters in the posterior cerebral artery (PCA) via the evaluation of latex angiographies. A stimulatory effect on arteriogenesis was investigated for ACEi administration ± bradykinin receptor 1 (B1R) and 2 (B2R) blockers, and an inhibitory effect was analysed for ARB administration. Results were validated by immunohistochemical analysis and mechanistic data were collected by human umbilical vein endothelial cell (HUVEC) viability or scratch assay and monocyte (THP‐1) migration assay.\n\n\nResults\nAn inhibitory effect of ARB on arteriogenesis could not be demonstrated. However, collateral growth measurements demonstrated a significantly increased CVRC and PCA diameters in the ACEi group. ACEi stimulates cell viability and migration, which could be partially reduced by additional administration of bradykinin receptor 1 inhibitor (B1Ri).\nACEi inhibits the degradation of pro‐arteriogenic bradykinin derivatives, but combined ACEi + B1Ri + B1Ri (BRB) treatment did not reverse the stimulatory effect. Yet, co‐administration of ACEi + BRB enhances arteriogenesis and cell migration.\n\n\nConclusion\nWe demonstrate a potent stimulatory effect of ACEi on cerebral arteriogenesis in rats, presumable via B1R. However, results imply a pleiotropic and compensatory effect of ACEi on bradykinin receptor‐stimulated arteriogenesis.\n\n"]

["Acta Physiologica, EarlyView. ", "\nAbstract\nThe molecular link between SARS‐CoV‐2 infection and susceptibility is not well understood. Nonetheless, a bi‐directional relationship between SARS‐CoV‐2 and diabetes has been proposed. The angiotensin‐converting enzyme 2 (ACE2) is considered as the primary protein facilitating SARS‐CoV and SARS‐CoV‐2 attachment and entry into the host cells. Studies suggested that ACE2 is expressed in the endocrine cells of the pancreas including beta cells, in addition to the lungs and other organs; however, its expression in the islets, particularly beta cells, has been met with some contradiction. Importantly, ACE2 plays a crucial role in glucose homoeostasis and insulin secretion by regulating beta cell physiology. Given the ability of SARS‐CoV‐2 to infect human pluripotent stem cell‐derived pancreatic cells in vitro and the presence of SARS‐CoV‐2 in pancreatic samples from COVID‐19 patients strongly hints that SARS‐CoV‐2 can invade the pancreas and directly cause pancreatic injury and diabetes. However, more studies are required to dissect the underpinning molecular mechanisms triggered in SARS‐CoV‐2‐infected islets that lead to aggravation of diabetes. Regardless, it is important to understand the function of ACE2 in the pancreatic islets to design relevant therapeutic interventions in combatting the effects of SARS‐CoV‐2 on diabetes pathophysiology. Herein, we detail the function of ACE2 in pancreatic beta cells crucial for regulating insulin sensitivity, secretion, and glucose metabolism. Also, we discuss the potential role played by ACE2 in aiding SARS‐COV‐2 entry into the pancreas and the possibility of ACE2 cooperation with alternative entry factors as well as how that may be linked to diabetes pathogenesis.\n"]

["Acta Physiologica, EarlyView. ", "\nAbstract\n\nAim\nWith diabetes comes a significant risk of macrovascular and microvascular complications. Circulating aldosterone levels increase in patients with diabetes. Aldosterone can directly affect vascular function via activation of the mineralocorticoid receptor (MR). We hypothesized that aldosterone via endothelial MR impairs endothelial function in a murine model of experimental diabetes.\n\n\nMethod\nEndothelial cell‐specific mineralocorticoid receptor knockout MRflox/flox;Tie2‐Cre mice (ECMR‐KO) and wild‐type FVB littermates were subjected to an experimental type‐1 diabetic model by low dose streptozotocin injections (55mg/kg/day) for five consecutive days. After 10 weeks of diabetes, second‐order mesenteric resistance arteries were perfused ex vivo to evaluate vessel contractility and endothelial function. The effect of ex vivo incubation with aldosterone with and without the antagonist, spironolactone was determined.\n\n\nResults\nDiabetic ECMR‐KO and wild‐type mice had similar, elevated, plasma aldosterone concentration while only diabetic wild‐type mice displayed elevated urine albumin excretion and cardiac and kidney hypertrophy at 10 weeks. There were no differences in contraction (Emax and EC50) to thromboxane receptor agonist (U46619) and elevated K+ between groups. Wild‐type diabetic mice showed impaired acetylcholine (ACh)‐dependent relaxation, while diabetic ECMR‐KO mice had intact ACh‐mediated relaxation. Aldosterone incubation ex vivo impaired ACh mediated relaxation and rendered responses similar to diabetic WT arteries. Direct, ex vivo aldosterone effects were absent in ECMR‐KO animals. Ex vivo inhibitory effects of aldosterone on endothelial relaxation in arteries from WT were abolished by spironolactone.\n\n\nConclusion\nThese findings show that endothelial cell mineralocorticoid receptor activation accounts for diabetes‐induced systemic endothelial dysfunction in experimental diabetes and may explain the cardiovascular protection by MR antagonists in diabetes.\n\n"]

["Acta Physiologica, EarlyView. ", "\nAbstract\n\nAim\nWe aimed at identifying potential roles of vesicular monoamine transporter 2, also known as Solute Carrier protein 18 A2 (SLC18A2) (hereafter, Vmat2), in brain monoamine regulation, their turnover, behaviour and brain development using a novel zebrafish model.\n\n\nMethods\nA zebrafish strain lacking functional Vmat2 was generated with the CRISPR/Cas9 system. Larval behaviour and heart rate were monitored. Monoamines and their metabolites were analysed with high‐pressure liquid chromatography. Amine synthesising and degrading enzymes, and genes essential for brain development, were analysed with quantitative PCR, in situ hybridisation and immunocytochemistry.\n\n\nResults\nThe 5‐bp deletion in exon 3 caused an early frameshift and was lethal within 2 weeks post‐fertilisation. Homozygous mutants (hereafter, mutants) displayed normal low locomotor activity during night‐time but aberrant response to illumination changes. In mutants dopamine, noradrenaline, 5‐hydroxytryptamine and histamine levels were reduced, whereas levels of dopamine and 5‐hydroxytryptamine metabolites were increased, implying elevated monoamine turnover. Consistently, there were fewer histamine, 5‐hydroxytryptamine and dopamine immunoreactive cells. Cellular dopamine immunostaining, in wild‐type larvae more prominent in tyrosine hydroxylase 1 (Th1)‐expressing than in Th2‐expressing neurons, was absent in mutants. Despite reduced dopamine levels, mutants presented upregulated dopamine‐synthesising enzymes. Further, in mutants the number of histidine decarboxylase‐expressing neurons was increased, notch1a and pax2a were downregulated in brain proliferative zones.\n\n\nConclusion\nLack of Vmat2 increases monoamine turnover and upregulates genes encoding amine‐synthesising enzymes, including histidine decarboxylase. Notch1a and pax2a, genes implicated in stem cell development, are downregulated in mutants. The zebrafish vmat2 mutant strain may be a useful model to study how monoamine transport affects brain development and function, and for use in drug screening.\n\n"]

["Acta Physiologica, Volume 232, Issue 4, August 2021. ", "\nAbstract\n\nAim\nMicroRNAs play an important role in the maintenance of cellular functions by fine‐tuning gene expression levels. The aim of the current study was to identify genetically caused changes in microRNA expression which associate with islet dysfunction in diabetic mice.\n\n\nMethods\nTo identify novel microRNAs involved in islet dysfunction, transcriptome and miRNome analyses were performed in islets of obese, diabetes‐susceptible NZO and diabetes‐resistant B6‐ob/ob mice and results combined with quantitative trait loci (QTL) and functional in vitro analysis.\n\n\nResults\nIn islets of NZO and B6‐ob/ob mice, 94 differentially expressed microRNAs were detected, of which 11 are located in diabetes QTL. Focusing on conserved microRNAs exhibiting the strongest expression difference and which have not been linked to islet function, miR‐205‐5p was selected for further analysis. According to transcriptome data and target prediction analyses, miR‐205‐5p affects genes involved in Wnt and calcium signalling as well as insulin secretion. Over‐expression of miR‐205‐5p in the insulinoma cell line INS‐1 increased insulin expression, left‐shifted the glucose‐dependence of insulin secretion and supressed the expression of the diabetes gene TCF7L2. The interaction between miR‐205‐5p and TCF7L2 was confirmed by luciferase reporter assay.\n\n\nConclusion\nMiR‐205‐5p was identified as relevant microRNA involved in islet dysfunction by interacting with TCF7L2.\n\n"]

["Acta Physiologica, Volume 232, Issue 4, August 2021. ", "\nAbstract\nGestational diabetes mellitus (GDM) shows a deficiency in the metabolism of D‐glucose and other nutrients, thereby negatively affecting the foetoplacental vascular endothelium. Maternal hyperglycaemia and hyperinsulinemia play an important role in the aetiology of GDM. A combination of these and other factors predisposes women to developing GDM with pre‐pregnancy normal weight, viz. classic GDM. However, women with GDM and prepregnancy obesity (gestational diabesity, GDty) or overweight (GDMow) show a different metabolic status than women with classic GDM. GDty and GDMow are associated with altered l‐arginine/nitric oxide and insulin/adenosine axis signalling in the human foetoplacental microvascular and macrovascular endothelium. These alterations differ from those observed in classic GDM. Here, we have reviewed the consequences of GDty and GDMow in the modulation of foetoplacental endothelial cell function, highlighting studies describing the modulation of intracellular pH homeostasis and the potential implications of NO generation and adenosine signalling in GDty‐associated foetal vascular insulin resistance. Moreover, with an increase in the rate of obesity in women of childbearing age worldwide, the prevalence of GDty is expected to increase in the next decades. Therefore, we emphasize that women with GDty and GDMow should be characterized with a different metabolic state from that of women with classic GDM to develop a more specific therapeutic approach for protecting the mother and foetus.\n"]

["Acta Physiologica, Volume 232, Issue 4, August 2021. ", "\nAbstract\n\nAim\nOur previous studies have demonstrated the importance of dietary factors in the determination of hypertension in Dahl salt‐sensitive (SS) rats. Since the gut microbiota has been implicated in chronic diseases like hypertension, we hypothesized that dietary alterations shift the microbiota to mediate the development of salt‐sensitive hypertension and renal disease.\n\n\nMethods\nThis study utilized SS rats from the Medical College of Wisconsin (SS/MCW) maintained on a purified, casein‐based diet (0.4% NaCl AIN‐76A, Dyets) and from Charles River Laboratories (SS/CRL) fed a whole grain diet (0.75% NaCl 5L79, LabDiet). Faecal 16S rDNA sequencing was used to phenotype the gut microbiota. Directly examining the contribution of the gut microbiota, SS/CRL rats were administered faecal microbiota transfer (FMT) experiments with either SS/MCW stool or vehicle (Vehl) in conjunction with the HS AIN‐76A diet.\n\n\nResults\nSS/MCW rats exhibit renal damage and inflammation when fed high salt (HS, 4.0% NaCl AIN‐76A), which is significantly attenuated in SS/CRL. Gut microbiota phenotyping revealed distinct profiles that correlate with disease severity. SS/MCW FMT worsened the SS/CRL response to HS, evidenced by increased albuminuria (67.4 ± 6.9 vs 113.7 ± 25.0 mg/day, Vehl vs FMT, P = .007), systolic arterial pressure (158.6 ± 5.8 vs 177.8 ± 8.9 mmHg, Vehl vs FMT, P = .09) and renal T‐cell infiltration (1.9‐fold). Amplicon sequence variant (ASV)‐based analysis of faecal 16S rDNA sequencing data revealed taxa that significantly shifted with FMT: Erysipelotrichaceae_2, Parabacteroides gordonii, Streptococcus alactolyticus, Bacteroidales_1, Desulfovibrionaceae_2, Ruminococcus albus.\n\n\nConclusions\nThese data demonstrate that dietary modulation of the gut microbiota directly contributes to the development of Dahl SS hypertension and renal injury.\n\n"]

["Acta Physiologica, Volume 232, Issue 4, August 2021. ", "\nAbstract\n\nAim\nThere is mounting evidence that TRPA1 has a role in cardiac physiology and pathophysiology. We aim to clarify the site of TRPA1 expression in the heart and in particular whether the channel is expressed in cardiomyocytes.\n\n\nMethods\nDue to the high calcium conductance of TRPA1, and marginal calcium changes being detectable, microfluorimetry in primary mouse cardiomyocytes, and in the cardiomyocyte cell lines H9c2 and HL‐1, was applied. TRPA1 mRNA in mouse and human hearts, primary cardiomyocytes, and the cardiac cell lines were quantified. Dorsal root ganglia served as control for both methods.\n\n\nResults\nIn addition to AITC, the more potent and specific TRPA1 agonists JT010 and PF‐4840154 failed to elicit a TRPA1‐mediated response in native and electrically paced primary cardiomyocytes, and the cardiomyocyte cell lines H9c2 and HL‐1. There were only marginal levels of TRPA1 mRNA in cardiomyocytes and cardiac cell lines, also in conditions of cell differentiation or inflammation, which might occur in pathophysiological conditions. Similarly, TRPV1 agonist capsaicin did not activate primary mouse cardiomyocytes, did not alter electrically paced activity in these, and did not activate H9c2 cells or alter spontaneous activity of HL‐1 cells. Human pluripotent stem cells differentiated to cardiomyocytes had no relevant TRPA1 mRNA levels. Also in human post‐mortem heart samples, TRPA1 mRNA levels were substantially lower compared with the respective dorsal root ganglion.\n\n\nConclusion\nThe results do not question a role of TRPA1 in the heart but exclude a direct effect in cardiomyocytes.\n\n"]

["Acta Physiologica, Volume 232, Issue 4, August 2021. ", "\nAbstract\n\nAim\nFluid and macromolecule transport from the interstitium into and through lymphatic vessels is necessary for tissue homeostasis. While lymphatic capillary structure suggests that passive, paracellular transport would be the predominant route of macromolecule entry, active caveolae‐mediated transcellular transport has been identified in lymphatic endothelial cells (LECs) in vitro. Caveolae also mediate a wide array of endothelial cell processes, including nitric oxide regulation. Thus, how does the lack of caveolae impact “lymphatic function”?\n\n\nMethods\nVarious aspects of lymphatic transport were measured in mice constitutively lacking caveolin‐1 (“CavKO”), the protein required for caveolae formation in endothelial cells, and in mice with a LEC‐specific Cav1 gene deletion (Lyve1‐Cre x Cav1flox/flox; “LyCav”) and ex vivo in their vessels and cells.\n\n\nResults\nIn each model, lymphatic architecture was largely unchanged. The lymphatic conductance, or initial tissue uptake, was significantly higher in both CavKO mice and LyCav mice by quantitative microlymphangiography and the permeability to 70 kDa dextran was significantly increased in monolayers of LECs isolated from CavKO mice. Conversely, transport within the lymphatic system to the sentinel node was significantly reduced in anaesthetized CavKO and LyCav mice. Isolated, cannulated collecting vessel studies identified significantly reduced phasic contractility when lymphatic endothelium lacks caveolae. Inhibition of nitric oxide synthase was able to partially restore ex vivo vessel contractility.\n\n\nConclusion\nMacromolecule transport across lymphatics is increased with loss of caveolae, yet phasic contractility reduced, resulting in reduced overall lymphatic transport function. These studies identify lymphatic caveolar biology as a key regulator of active lymphatic transport functions.\n\n"]

["Acta Physiologica, EarlyView. ", "\nAbstract\n\nAim\nWe aimed to evaluate whether the streptozotocin‐induced diabetic model can generate lung functional, histological and biochemical impairments and whether moderate exercise can prevent these changes.\n\n\nMethods\nWistar rats were assigned to control (CTRL), exercise (EXE), diabetic (D) and diabetic with exercise (D+EXE) groups. We used the n5‐STZ model of diabetes mellitus triggered by a single injection of streptozotocin (STZ, 120 mg/kg b.w., i.p.) in newborn rats on their 5th day of life. EXE and D+EXE rats were trained by running on a motorized treadmill, 5 days a week for 9 weeks. Blood glucose, body weight, food intake, exercise capacity, lung mechanics, morphology, and antioxidant enzymatic activity were analysed.\n\n\nResults\nOn the 14th week of life, diabetic rats exhibited a significant impairment in post‐prandial glycaemia, glucose tolerance, body weight, food intake, lung function (tissue viscance, elastance, Newtonian resistance and hysteresis), morphological parameters, redox balance and exercise capacity. Physical training completely prevented the diabetes‐induced alterations, except for those on fasting blood glucose, which nevertheless remained stable.\n\n\nConclusions\nMild diabetes in n5‐STZ‐treated rats jeopardized pulmonary mechanics, morphology and redox balance, which confirms the occurrence of diabetes‐induced pneumopathy. Moreover, moderate exercise completely prevented all diabetes‐induced respiratory alterations.\n\n"]

["Acta Physiologica, EarlyView. ", "\nAbstract\n\nAim\nCardiac arrhythmias and sudden deaths have diurnal rhythms in humans. The underlying mechanisms are unknown. Mice with cardiomyocyte‐specific disruption of the molecular clock genes have lower heart rate than control. Because changes in the QT interval on the electrocardiogram is a clinically used marker of risk of arrhythmias, we sought to test if the biological rhythms of QT intervals are dependent on heart rate and if this dependency is changed when the molecular clock is disrupted.\n\n\nMethods\nWe implanted radio transmitters in male mice with cardiomyocyte‐specific Bmal1 knockout (CBK) and in control mice and recorded 24‐h ECGs under diurnal and circadian conditions. We obtained left ventricular monophasic action potentials during pacing in hearts ex vivo.\n\n\nResults\nBoth RR and QT intervals were longer in conscious CBK than control mice (RR: 117 ± 7 vs 110 ± 9 ms, P < .05; and QT: 53 ± 4 vs 48 ± 2 ms, P < .05). The prolonged QT interval was independent of the slow heart rate in CBK mice. The QT interval exhibited diurnal and circadian rhythms in both CBK and control mice. The action potential duration was longer in CBK than in control mice, indicating slower repolarization. Action potential alternans occurred at lower pacing rate in hearts from CBK than control mice (12 ± 3 vs 16 ± 2 Hz, respectively, P < .05).\n\n\nConclusion\nThe bradycardic CBK mice have prolonged ventricular repolarization independent of the heart rate. Diurnal and circadian rhythms in repolarization are preserved in CBK mice and are not a consequence of the 24‐h rhythm in heart rate. Arrhythmia vulnerability appears to be increased when the cardiac clock is disrupted.\n\n"]

["Acta Physiologica, Volume 232, Issue 3, July 2021. ", "\nAbstract\nCa2+ mishandling is a common feature in several cardiovascular diseases such as heart failure (HF). In many cases, impairment of key players in intracellular Ca2+ homeostasis has been identified as the underlying mechanism of cardiac dysfunction and cardiac arrhythmias associated with HF. In this review, we summarize primary novel findings related to Ca2+ mishandling in HF progression. HF research has increasingly focused on the identification of new targets and the contribution of their role in Ca2+ handling to the progression of the disease. Recent research studies have identified potential targets in three major emerging areas implicated in regulation of Ca2+ handling: the innate immune system, bone metabolism factors and post‐translational modification of key proteins involved in regulation of Ca2+ handling. Here, we describe their possible contributions to the progression of HF.\n"]

["Acta Physiologica, Volume 232, Issue 3, July 2021. ", "\nAbstract\nIn arterial smooth muscle cells, changes in availability of integral membrane proteins influence the regulation of blood flow and blood pressure, which is critical for human health. However, the mechanisms that coordinate the trafficking and membrane expression of specific receptors and ion channels in vascular smooth muscle are poorly understood. In the vasculature, very little is known about microtubules, which form a road network upon which proteins can be transported to and from the cell membrane. This review article summarizes the impact of the microtubule network on arterial contractility, highlighting the importance of the network, with an emphasis on our recent findings regarding the trafficking of the voltage‐dependent Kv7 channels.\n"]

["Acta Physiologica, Volume 232, Issue 3, July 2021. ", "\nAbstract\n\nAim\nGlial fibrillary acidic protein (GFAP) molecularly associates with aquaporin 4 (AQP4) in astrocytic plasticity. Here, we further examined how AQP4 modulates osmotic effects on vasopressin (VP) neurons in rat supraoptic nucleus (SON) through interactions with GFAP in astrocytes.\n\n\nMethods\nBrain slices from adult male rats were kept under osmotic stimulation. Western blot, co‐immunoprecipitation, immunohistochemistry and patch‐clamp recordings were used for analysis of expressions and interactions between GFAP and AQP4, astrocyte‐specific proteins in the SON, as well as their influence on VP neuronal activity. Data were analysed using SPSS software.\n\n\nResults\nHyposmotic challenge (HOC) of acute SON slices caused an early (within 5 minutes) and transient increase in the colocalization of AQP4 with GFAP filaments. This effect was prominent at astrocytic processes surrounding VP neuron somata and was accompanied by inhibition of VP neuronal activity. Similar HOC effect was seen in the SON isolated from rats subjected to in vivo HOC, wherein a transiently increased molecular association between GFAP and AQP4 was detected using co‐immunoprecipitation. The late stage rebound excitation (10 minutes) of VP neurons in brain slices subjected to HOC and the associated astrocytic GFAP’s ‘return to normal’ were both hampered by 2‐(nicotinamide)‐1,3,4‐thiadiazole, a specific AQP4 channel blocker that itself did not influence VP neuronal activity. Moreover, this agent prevented hyperosmotic stress‐evoked excitation of VP neurons and associated reduction in GFAP filaments.\n\n\nConclusion\nThese findings indicate that osmotically driven increase in VP neuronal activity requires the activation of AQP4, which determines a retraction of GFAP filaments.\n\n"]

["Acta Physiologica, Volume 232, Issue 3, July 2021. ", "\nAbstract\n\nAim\nMitophagy is the regulated process that targets damaged or dysfunctional mitochondria for lysosomal‐mediated removal. This process is an essential element of mitochondrial quality control, and dysregulation of mitophagy may contribute to a host of diseases, most notably neurodegenerative conditions such as Parkinson's disease. Mitochondria targeted for mitophagic destruction are molecularly marked by the ubiquitination of several outer mitochondrial membrane (OMM) proteins. This ubiquitination is positively regulated, in part, by the mitochondrial‐targeted kinase PINK1 and the E3 ubiquitin ligase Parkin. In contrast, the reverse phenomenon, deubiquitination, removes ubiquitin from Parkin substrates embedded in the OMM proteins, antagonizing mitophagy. Recent evidence suggests that the mitochondrial deubiquitinase USP30 negatively regulates Parkin‐mediated mitophagy, providing opportunities to identify USP30 inhibitors and test for their effects in augmenting mitophagy. Here we will characterize a USP30 inhibitor and demonstrate how the pharmacological inhibition of USP30 can augment stress‐induced mitophagic flux.\n\n\nMethods\nWe have conducted mitophagy and mitochondrial analyses in cultured cells. We have determined the plasma pharmacokinetics of the USP30 inhibitor in mice and conducted analyses using the mt‐Keima mice to measure in vivo mitophagy directly.\n\n\nResults\nThe compound has minimal mitochondrial toxicity in cultured cells and is tolerated well in mice. Interestingly, we demonstrated tissue‐specific induction of mitophagy following USP30 pharmacological inhibition. In particular, pharmacological inhibition of USP30 induces a significant increase in cardiac mitophagy without detriment to cardiac function.\n\n\nConclusion\nOur data support the evidence that USP30 inhibition may serve as a specific strategy to selectively increase mitophagic flux, allowing for the development of novel therapeutic approaches.\n\n"]

["Acta Physiologica, Volume 232, Issue 3, July 2021. ", "\nAbstract\n\nAim\nType A intercalated cells of the renal collecting duct participate in the maintenance of the acid/base balance through their capacity to adapt proton secretion to homeostatic requirements. We previously showed that increased proton secretion stems in part from the enlargement of the population of proton secreting cells in the outer medullary collecting duct through division of fully differentiated cells, and that this response is triggered by growth/differentiation factor 15. This study aimed at deciphering the mechanism of acid load‐induced secretion of Gdf15 and its mechanism of action.\n\n\nMethods\nWe developed an original method to evaluate the proliferation of intercalated cells and applied it to genetically modified or pharmacologically treated mice under basal and acid‐loaded conditions.\n\n\nResults\nGdf15 is secreted by principal cells of the collecting duct in response to the stimulation of vasopressin receptors. Vasopressin‐induced production of cAMP triggers activation of AMP‐stimulated kinases and of Na,K‐ATPase, and induction of p53 and Gdf15. Gdf15 action on intercalated cells is mediated by ErbB2 receptors, the activation of which triggers the expression of cyclin d1, of p53 and anti‐proliferative genes, and of Egr1.\n\n\nConclusion\nAcidosis‐induced proliferation of intercalated cells results from a cross talk with principal cells which secrete Gdf15 in response to their stimulation by vasopressin. Thus, vasopressin is a major determinant of the collecting duct cellular homeostasis as it promotes proliferation of intercalated cells under acidosis conditions and of principal cells under normal acid‐base status.\n\n"]

["Acta Physiologica, Volume 232, Issue 3, July 2021. ", "\nAbstract\nSystemic arterial hypertension and heart failure are cardiovascular diseases that affect millions of individuals worldwide. They are characterized by a change in the autonomic nervous system balance, highlighted by an increase in sympathetic activity associated with a decrease in parasympathetic activity. Most therapeutic approaches seek to treat these diseases by medications that attenuate sympathetic activity. However, there is a growing number of studies demonstrating that the improvement of parasympathetic function, by means of pharmacological or electrical stimulation, can be an effective tool for the treatment of these cardiovascular diseases. Therefore, this review aims to describe the advances reported by experimental and clinical studies that addressed the potential of cholinergic stimulation to prevent autonomic and cardiovascular imbalance in hypertension and heart failure. Overall, the published data reviewed demonstrate that the use of central or peripheral acetylcholinesterase inhibitors is efficient to improve the autonomic imbalance and hemodynamic changes observed in heart failure and hypertension. Of note, the baroreflex and the vagus nerve activation have been shown to be safe and effective approaches to be used as an alternative treatment for these cardiovascular diseases. In conclusion, pharmacological and electrical stimulation of the parasympathetic nervous system has the potential to be used as a therapeutic tool for the treatment of hypertension and heart failure, deserving to be more explored in the clinical setting.\n"]

["Acta Physiologica, Volume 232, Issue 3, July 2021. ", "\nAbstract\n\nAim\nHighly prevalent diseases such as insulin resistance and heart failure are characterized by reduced metabolic flexibility and reserve. We tested whether Na/K‐ATPase (NKA)‐mediated regulation of Src kinase, which requires two NKA sequences specific to the α1 isoform, is a regulator of metabolic capacity that can be targeted pharmacologically.\n\n\nMethods\nMetabolic capacity was challenged functionally by Seahorse metabolic flux analyses and glucose deprivation in LLC‐PK1‐derived cells expressing Src binding rat NKA α1, non‐Src‐binding rat NKA α2 (the most abundant NKA isoform in the skeletal muscle), and Src binding gain‐of‐function mutant rat NKA α2. Mice with skeletal muscle‐specific ablation of NKA α1 (skα1−/−) were generated using a MyoD:Cre‐Lox approach and were subjected to treadmill testing and Western diet. C57/Bl6 mice were subjected to Western diet with or without pharmacological inhibition of NKA α1/Src modulation by treatment with pNaKtide, a cell‐permeable peptide designed by mapping one of the sites of NKA α1/Src interaction.\n\n\nResults\nMetabolic studies in mutant cell lines revealed that the Src binding regions of NKA α1 are required to maintain metabolic reserve and flexibility. Skα1−/− mice had decreased exercise endurance and mitochondrial Complex I dysfunction. However, skα1−/− mice were resistant to Western diet‐induced insulin resistance and glucose intolerance, a protection phenocopied by pharmacological inhibition of NKA α1‐mediated Src regulation with pNaKtide.\n\n\nConclusions\nThese results suggest that NKA α1/Src regulatory function may be targeted in metabolic diseases. Because Src regulatory capability by NKA α1 is exclusive to endotherms, it may link the aerobic scope hypothesis of endothermy evolution to metabolic dysfunction.\n\n"]

["Acta Physiologica, Volume 232, Issue 3, July 2021. ", "\nAbstract\n\nAims\nTotal haemoglobin mass (tot‐Hb) increases during high‐altitude acclimatization. Normalization of tot‐Hb upon descent is thought to occur via neocytolysis, the selective destruction of newly formed erythrocytes. Because convincing experimental proof of neocytolysis is lacking, we performed a prospective study on erythrocyte survival after a stay at the Jungfraujoch Research Station (JFJRS; 3450 m).\n\n\nMethods\nNewly formed erythrocytes of 12 male subjects (mean age 23.3 years) were age cohort labelled in normoxia (110 m) and during a 19‐day high‐altitude sojourn by ingestion of 13C2‐ and 15N‐labelled glycine respectively. Elimination dynamics for erythrocytes produced in normoxia and at high altitude were measured by isotope ratio mass spectrometry of haem, by determining tot‐Hb, reticulocyte counts, erythrocyte membrane protein 4.1a/4.1b ratio and by mathematical modelling.\n\n\nResults\nTot‐Hb increased by 4.7% ± 2.7% at high altitude and returned to pre‐altitude values within 11 days after descent. Elimination of 13C‐ (normoxia) and 15N‐ (high altitude) labelled erythrocytes was not different. Erythropoietin levels and counts of CD71‐positive reticulocytes decreased rapidly after descent. The band 4.1a/4.1b ratio decreased at altitude and remained low for 3‐4 days after descent and normalized slowly. There was no indication of haemolysis.\n\n\nConclusion\nWe confirm a rapid normalization of tot‐Hb upon descent. Based on the lack of accelerated removal of age cohorts of erythrocytes labelled at high altitude, on patterns of changes in reticulocyte counts and of the band 4.1a/4.1b ratio and on modelling, this decrease did not occur via neocytolysis, but by a reduced rate of erythropoiesis along with normal clearance of senescent erythrocytes.\n\n"]

["Acta Physiologica, EarlyView. ", "\nAbstract\n\nAim\nThe phosphorylation level of the furosemide‐sensitive Na+‐K+‐2Cl− cotransporter (NKCC2) in the thick ascending limb (TAL) is used as a surrogate marker for NKCC2 activation and TAL function. However, in mice, analyses of NKCC2 phosphorylation with antibodies against phosphorylated threonines 96 and 101 (anti‐pT96/pT101) give inconsistent results. We aimed (a) to elucidate these inconsistencies and (b) to develop a phosphoform‐specific antibody that ensures reliable detection of NKCC2 phosphorylation in mice.\n\n\nMethods\nGenetic information, molecular biology, biochemical techniques and mouse phenotyping was used to study NKCC2 and kidney function in two commonly used mouse strains (ie 129Sv and in C57BL/6 mice). Moreover, a new phosphoform‐specific mouse NKCC2 antibody was developed and characterized.\n\n\nResults\nAmino acids sequence alignment revealed that C57BL/6 mice have a strain‐specific five amino acids deletion (ΔF97‐T101) in NKCC2 that diminishes the detection of NKCC2 phosphorylation with previously developed pT96/pT101 NKCC2 antibodies. Instead, the antibodies cross‐react with the phosphorylated thiazide‐sensitive NaCl cotransporter (NCC), which can obscure interpretation of results. Interestingly, the deletion in NKCC2 does not impact on kidney function and/or expression of renal ion transport proteins as indicated by the analysis of the F2 generation of crossbred 129Sv and C57BL/6 mice. A newly developed pT96 NKCC2 antibody detects pNKCC2 in both mouse strains and shows no cross‐reactivity with phosphorylated NCC.\n\n\nConclusion\nOur work reveals a hitherto unappreciated, but essential, strain difference in the amino acids sequence of mouse NKCC2 that needs to be considered when analysing NKCC2 phosphorylation in mice. The new pNKCC2 antibody circumvents this technical caveat.\n\n"]

["Acta Physiologica, EarlyView. ", "\nAbstract\n\nAim\nChronodisruption desynchronizes peripheral clocks and leads to metabolic diseases. Feeding cues are important synchronizers of peripheral clocks and influence rhythmic oscillations in intestinal microbiota and their metabolites. We investigated whether chronic jetlag, mimicking frequent time zone travelling, affected the diurnal fluctuations in faecal short‐chain fatty acid (SCFA) levels, that feed back to the gut clock to regulate rhythmicity in gut function.\n\n\nMethods\nRhythms in faecal SCFAs levels and in the expression of clock genes and epithelial markers were measured in the colonic mucosa of control and jetlagged mice. The entraining effect of SCFAs on the rhythm in clock gene mRNA expression was studied in primary colonic crypts. The role of the circadian clock in epithelial marker expression was studied in Arntl−/− mice.\n\n\nResults\nChronic jetlag increased body weight gain and abolished the day/night food intake pattern which resulted in a phase‐delay in the rhythm of faecal SCFAs that paralleled the shift in the expression of mucosal clock genes. This effect was mimicked by stimulation of primary colonic crypts from control mice with SCFAs. Jetlag abolished the rhythm in Tnfα, proglucagon and ghrelin expression but not in the expression of tight junction markers. Only a dampening in plasma glucagon‐like peptide‐1 but not in ghrelin levels was observed. Rhythms in ghrelin but not proglucagon mRNA expression were abolished in Arntl−/− mice.\n\n\nConclusion\nThe altered food intake pattern during chronodisruption corresponds with the changes in rhythmicity of SCFA levels that entrain clock genes to affect rhythms in mRNA expression of gut epithelial markers.\n\n"]