A novel Ca2+ double cone vector system to treat compromised skin.

BACKGROUND: Stressed, damaged or very aged skin is predominantly characterized by a malfunctioning skin barrier. Underlying skin barrier malfunction is a reduced or defective calcium gradient in the epidermis. Consequently, replenishing the compromised skin's calcium stores with topical calcium could be a potential therapeutic approach. METHODS: We investigated the effect of our novel Ca2+ double cone vector system on improving the differentiation and barrier function of reconstructed human epidermis (RHE), cultured at low basal calcium (0.3 mM) to represent very aged skin. Furthermore, in a randomized placebo-controlled clinical study the skin barrier of 20 healthy volunteers was challenged with 2% sodium lauryl sulphate (SLS) for 24 h under occlusion, following and/or prior to treatment with a gel containing 2% of our calcium vector system. RESULTS: Culture in reduced basal calcium conditions (0.3 mM) strongly impeded the formation of a dense stratified epidermis. The apical treatment with 1.1 mM CaCl2 was not able to restore a functional differentiation. Treatment with 0.1% of the Ca2+ delivery system rescued the differentiation process and resulted in a normal stratified epidermis. Clinically, application of the Ca2+ vector system prior to and following SLS stress prevented increases in skin irritation and transepidermal water loss (TEWL) compared to placebo controls. Importantly, the treatment also significantly accelerated the recovery time following SLS stress. CONCLUSION: With our novel Ca2+ vector system, we highlight the delivery of bioavailable Ca2+ ions into the skin as a new and successful approach to treat a damaged barrier present in stressed, aged or atopic skin.

CONTEXTE: Les peaux stressées, lésées ou très âgées se caractérisent principalement par un dysfonctionnement de la barrière cutanée. Le dysfonctionnement de la barrière cutanée est sous­tendu par un gradient de calcium réduit ou défectueux dans l'épiderme. Par conséquent, la reconstitution des réserves de calcium de la peau fragilisées à l'aide de calcium topique pourrait constituer une approche thérapeutique potentielle. MÉTHODES: Nous avons étudié l'effet de notre nouveau système de vecteur à double cône Ca2+ sur l'amélioration de la différenciation et de la fonction de barrière de l'épiderme humain reconstitué (EHR), cultivé à un faible niveau de calcium basal (0,3 mM) pour représenter une peau très âgée. En outre, dans une étude clinique randomisée, contrôlée par placebo, la barrière cutanée de 20 volontaires en bonne santé a été exposée à 2 % de laurylsulfate de sodium (SLS) pendant 24 heures sous occlusion, après et/ou avant le traitement avec un gel contenant 2 % de notre système de vecteur de calcium. RÉSULTATS: La culture dans des conditions de calcium basal réduit (0,3 mM) a fortement empêché la formation d'un épiderme stratifié dense. Le traitement apical avec 1,1 mM de CaCl2 n'a pas permis de rétablir une différenciation fonctionnelle. Le traitement avec 0,1 % du système de libération de Ca2+ a permis de rétablir le processus de différenciation et d'obtenir un épiderme stratifié normal. Sur le plan clinique, l'application du système de vecteur Ca2+ avant et après l'exposition au SLS a empêché l'augmentation de l'irritation cutanée et de la perte d'eau transépidermique (Transepidermal Water Loss, TEWL) par rapport aux témoins sous placebo. Il est important de noter que le traitement a également accéléré de manière significative le temps de récupération après l'exposition au SLS. CONCLUSION: Grâce à notre nouveau système de vecteurs Ca2+, nous mettons en évidence l'apport d'ions Ca2+ biodisponibles dans la peau comme une approche nouvelle et efficace pour traiter la barrière endommagée présente dans une peau stressée, âgée ou atopique.

Cryptic diversity within the Poecilochirus carabi mite species complex phoretic on Nicrophorus burying beetles: Phylogeny, biogeography, and host specificity.

Coevolution is often considered a major driver of speciation, but evidence for this claim is not always found because diversity might be cryptic. When morphological divergence is low, molecular data are needed to uncover diversity. This is often the case in mites, which are known for their extensive and often cryptic diversity. We studied mites of the genus Poecilochirus that are phoretic on burying beetles (Silphidae: Nicrophorus). Poecilochirus taxonomy is poorly understood. Most studies on this genus focus on the evolutionary ecology of Poecilochirus carabi sensu lato, a complex of at least two biological species. Based on molecular data of 230 specimens from 43 locations worldwide, we identified 24 genetic clusters that may represent species. We estimate that these mites began to diversify during the Paleogene, when the clade containing P. subterraneus branched off and the remaining mites diverged into two further clades. One clade resembles P. monospinosus. The other clade contains 17 genetic clusters resembling P. carabi s.l.. Among these are P. carabi sensu stricto, P. necrophori, and potentially many additional cryptic species. Our analyses suggest that these clades were formed in the Miocene by large-scale geographic separation; co-speciation of mites with the host beetles can be largely ruled out. Diversification also seems to have happened on a smaller scale, potentially due to adaptation to specific hosts or local abiotic conditions, causing some clusters to specialize on certain beetle species. Our results suggest that biodiversity in this genus was generated by multiple interacting forces shaping the tangled webs of life.

The impact of the COVID-19 pandemic on treatment-seeking veterans in the United Kingdom with preexisting mental health difficulties: A longitudinal study.

Individuals with preexisting psychological difficulties are at risk of further deterioration of their mental well-being during the COVID-19 pandemic. This longitudinal study, conducted during the period between two national lockdowns, aimed to investigate the impact of the COVID-19 pandemic on veterans in the United Kingdom with preexisting mental health difficulties. Treatment-seeking veterans with preexisting mental health difficulties (N = 95) were surveyed in two waves. Wave 1 was conducted at the end of the first lockdown (June 2020-July 2020), and Wave 2 took place during the second lockdown (November 2020). Participants completed measures to assess symptoms of posttraumatic stress disorder (PTSD); common mental health difficulties (CMDs), including anxiety and depression; anger; and alcohol use. Initial analyses revealed no significant changes in symptoms of PTSD, CMDs, anger, or alcohol use between the lockdowns, ps = .247-.986. However, veterans who experienced more COVID-19-related stressors were more likely to experience increases in PTSD, odds ratio (OR) = 6.30, p = .002, and CMD symptoms, OR = 4.32, p = .025. Participants with lower levels of social support during the second lockdown were more likely to experience increased anger difficulties, OR = 0.91, p = .025. The findings suggest that although mental health among veterans in the United Kingdom may have remained relatively stable between the two lockdowns, those who reported more COVID-related stressors and lower levels of social support may have been particularly vulnerable to symptom exacerbation. Such findings hold important implications for tailoring support for veterans during the COVID-19 pandemic.

Pericyte hypoxia-inducible factor-1 (HIF-1) drives blood-brain barrier disruption and impacts acute ischemic stroke outcome.

Pericytes play essential roles in blood-brain barrier integrity and their dysfunction is implicated in neurological disorders such as stroke although the underlying mechanisms remain unknown. Hypoxia-inducible factor-1 (HIF-1), a master regulator of injury responses, has divergent roles in different cells especially during stress scenarios. On one hand HIF-1 is neuroprotective but on the other it induces vascular permeability. Since pericytes are critical for barrier stability, we asked if pericyte HIF-1 signaling impacts barrier integrity and injury severity in a mouse model of ischemic stroke. We show that pericyte HIF-1 loss of function (LoF) diminishes ischemic damage and barrier permeability at 3 days reperfusion. HIF-1 deficiency preserved barrier integrity by reducing pericyte death thereby maintaining vessel coverage and junctional protein organization, and suppressing vascular remodeling. Importantly, considerable improvements in sensorimotor function were observed in HIF-1 LoF mice indicating that better vascular functionality post stroke improves outcome. Thus, boosting vascular integrity by inhibiting pericytic HIF-1 activation and/or increasing pericyte survival may be a lucrative option to accelerate recovery after severe brain injury.

A taxonomist's nightmare - Cryptic diversity in Caribbean intertidal arthropods (Arachnida, Acari, Oribatida).

There has been a long controversy about what defines a species and how to delimitate them which resulted in the existence of more than two dozen different species concepts. Recent research on so-called "cryptic species" heated up this debate as some scientists argue that these cryptic species are only a result of incompatible species concepts. While this may be true, we should keep in mind that all concepts are nothing more than human constructs and that the phenomenon of high phenotypic similarity despite reproductive isolation is real. To investigate and understand this phenomenon it is important to classify and name cryptic species as it allows to communicate them with other fields of science that use Linnaean binomials. To provide a common framework for the description of cryptic species, we propose a possible protocol of how to formally name and describe these taxa in practice. The most important point of this protocol is to explain which species concept was used to delimitate the cryptic taxon. As a model, we present the case of the allegedly widespread Caribbean intertidal mite Thalassozetes barbara, which in fact consists of seven phenotypically very similar but genetically distinct species. All species are island or short-range endemics with poor dispersal abilities that have evolved in geographic isolation. Stabilizing selection caused by the extreme conditions of the intertidal environment is suggested to be responsible for the morphological stasis of this cryptic species complex.

Patterns of intraspecific morphological variability in soil mites reflect their dispersal ability.

The ability to disperse is one of the most important factors influencing the biogeography of species and speciation processes. Highly mobile species have been shown to lack geographic population structures, whereas less mobile species show genetically strongly subdivided populations which are expected to also display at least subtle phenotypic differences. Geometric morphometric methods (GMM) were now used to analyze morphological differences between European populations of a presumed non-phoretic, little mobile mite species in comparison to a highly mobile, phoretic species. The non-phoretic species Scutacarus carinthiacus showed a phenotypic population structure, whereas the phoretic species S. acarorum displayed homogeneity. These different patterns most probably can be explained by different levels of gene flow due to different dispersal abilities of the two species. GMM proved to be a sensitive tool that is especially recommendable for the analysis of (old) museum material and/or specimens in microscopic slides, which are not suitable for molecular genetic analysis.

Furin inhibition prevents hypoxic and TGFß-mediated blood-brain barrier disruption.

Hypoxic blood-brain barrier (BBB) dysfunction is a common feature of CNS diseases however mechanisms underlying barrier disturbance are still largely unknown. This study investigated the role of transforming growth factor ß (TGFß), a cytokine known to induce expression of the proprotein convertase Furin, in hypoxia-mediated barrier compromise. We show that exposure of brain endothelial cells (ECs) to hypoxia (1% O2) rapidly stimulates their migration. Additional exogenous TGFß (0.4 nM) exposure potentiated this effect and increased Furin expression in a TGFß type I receptor activin-like kinase 5 (ALK5) - dependent manner (prevented by 10 µM SB431542). Furin inhibition prevented hypoxia-induced EC migration and blocked TGFß-induced potentiation suggesting existence of a feedback loop. TGFß and Furin were also critical for hypoxia-induced BBB dysfunction. TGFß treatment aggravated hypoxia-induced BBB permeability but ALK5 or Furin blockade reversed injury-induced permeability changes. Thus during insult Furin compromises endothelial integrity by mediating the effects of TGFß. Targeting the Furin or ALK5 pathway may offer novel therapeutic strategies for improving BBB stability and CNS function during disease.

The Caribbean enigma: the presence of unusual cryptic diversity in intertidal mites (Arachnida, Acari, Oribatida).

The definition, as well as the existence of cryptic species, is still a subject of controversial debates. Some scientists claim that cryptic diversity is a real phenomenon that should be extensively studied while others argue that cryptic species do not exist as they are nothing more than an incompatibility of species concepts. We investigated the enigmatic case of two widely distributed Caribbean intertidal oribatid mites, Carinozetes bermudensis and Carinozetes mangrovi, consisting of five distinct genetic lineages. Morphological features allowing to clearly distinguish between these lineages are absent, and despite certain congruence with genetic data, comprehensive morphometric analyses also do not show clear separation. Species delimitation analyses based on COI sequence data, on the other hand, suggest five distinct genetic species. Despite the lack of diagnostic characters for these suggested species, the lineages can be classified at least into two morphological groups, the bermudensis and the mangrovi group which can only be distinguished by the arrangement of cuticular ventral carinae. Specimens within a group show nearly identical phenotypes, impeding morphological identification and hence rendering the found diversity cryptic. Stabilizing selection caused by the extreme conditions of the intertidal environment is suggested to be responsible for the found morphological stasis. The genetic lineages show more or less clear geographic patterns; in C. mangrovi, there is a northern, an Antillean, and a Pacific lineage, whereas in C. bermudensis, there is a Bermudian and a Caribbean lineage. In a few places, e.g., the Bahamas and Panama, distributions may overlap. Neither the found biogeographic pattern nor the observed ecological needs could explain the reason for the genetic diversification of Caribbean Carinozetes.

New and cryptic species of intertidal mites (Acari, Oribatida) from the Western Caribbean - an integrative approach.

The present study highlights the distribution, systematics, morphology, genetics, and ecology of two newly discovered intertidal oribatid mites from the Western Caribbean. The fortuyniid Litoribates floridae sp. nov. represents a cryptic species as it looks nearly identical to L. bonairensis. The two species can be distinguished only by subtle morphological and morphometric characteristics, whereas cytochrome oxidase subunit I gene sequences clearly separate the two taxa. The absence of morphological divergence in these disjunct species may have resulted from stabilizing selection due to the extreme intertidal environment. Litoribates floridae sp. nov. is presently known from the Florida Keys, primarily in mangrove leaf litter. The selenoribatid Thalassozetes balboa sp. nov. can be distinguished from all known congeners by a unique cuticular notogastral pattern, the presence of only two pairs of adanal setae, and two ventral teeth on each leg claw. It is morphologically most similar to T. barbara from the Eastern Caribbean. Thalassozetes balboa sp. nov. was found in Panama and Florida. This species usually occurs on rocky substrate and feeds on the intertidal alga Bostrychia. Litoribates floridaehttp://www.zoobank.org/urn:lsid:zoobank.org:act:A4B830FC-A03F-405D-9DE4-DE4C39DB6211 Thalassozetes balboahttp://www.zoobank.org/urn:lsid:zoobank.org:act:EBF8C435-5C07-4B0E-8279-2101DC9E2CD4.

Morphological diversification among island populations of intertidal mites (Acari, Oribatida, Fortuyniidae) from the Galápagos archipelago.

The intertidal oribatid mite species Alismobates galapagoensis and Litoribates caelestis occur on the archipelago of Galápagos. To test for morphological variation between populations of different islands, a comprehensive morphometric study was performed. Four A. galapagoensis populations from the islands Bartolomé, Isabela, Santa Cruz and San Cristobal, as well as two L. caelestis populations from Bartolomé and Santa Cruz were investigated. The L. caelestis populations did not show any significant differences whereas the A. galapagoensis populations exhibited clear divergences indicating speciation. Differences in overall size of A. galapagoensis apparently followed a gradient from East to West, with specimens from San Cristóbal being the largest and individuals from Bartolomé and Isabela being the smallest. Apart from size, significant shape differences were found in the epimeral region and females showed stronger variation among islands than males. The degree of morphological divergence seems to correlate with geographic distance, i.e. populations from islands located closer to each other showed fewer differences than populations from distant islands. Based on this correlation we suggest that transport between islands has happened mainly by drifting on ocean currents.

Oral distension methods for small bowel MRI: comparison of different agents to optimize bowel distension.

Background Different methods for bowel distension prior to magnetic resonance imaging (MRI) examinations were described in recent years. Purpose To compare orally administered psyllium or locust bean gum / mannitol (LBM) with tylose administered through a duodenal catheter for bowel distension in patients undergoing MRI examination of the small bowel. Material and Methods Three different methods of bowel distension prior to MRI were compared: tylose applied through a duodenal catheter and orally administered psyllium and LBM in three groups with 15 patients each. Datasets were blinded and reviewed independently by two experienced radiologists, who assessed the diagnostic value and the maximum luminal diameter. Results Tylose was superior to psyllium and LBM in the examination of the duodenum and proximal jejunum. LBM was superior to the other methods for distension of the ileum and terminal ileum. The greatest luminal diameter of the duodenum was achieved after tylose and distension of the terminal ileum was the best in patients receiving LBM. The psyllium group was inferior to the other two groups in all segments. Conclusion By using LBM as an oral method of bowel distension, many patients can avoid the unpleasant placement of a duodenal catheter without compromising the diagnostic value of the examination.

Lack of cross-protection against Mycoplasma haemofelis infection and signs of enhancement in "Candidatus Mycoplasma turicensis"-recovered cats.

"Mycoplasma haemofelis" and "Candidatus Mycoplasma turicensis" are feline hemoplasmas that induce hemolytic anemia. Protection from homologous re-challenge was recently demonstrated in cats recovered from primary infection. Here, we determined if cats recovered from "Cand. M. turicensis" infection were protected against infections with the more pathogenic M. haemofelis. Ten specified pathogen-free cats were exposed to M. haemofelis. Five of the ten cats had recovered from "Cand. M. turicensis" bacteremia (group A), and five cats were naïve controls (group B). No cross-protection was observed. By contrast, the "Cand. M. turicensis"-recovered cats displayed faster M. haemofelis infection onset (earlier PCR-positive and anemic) than the controls. No "Cand. M. turicensis" was detected in any cat. M. haemofelis shedding was observed in saliva, feces and urine. In both groups, evidence of a Th1 response was observed (high IFN-γ, low IL-4), but IL-10 levels were also high. In group A, total, CD4+ and CD8+ T cells increased within days after M. haemofelis exposure. At times of maximal bacteremia, macrocytic hypochromic anemia, neutropenia, monocytosis and a decrease in leukocyte, eosinophil, and lymphocyte counts and subsets thereof (B- and T-cells, CD4+, CD8+ and CD4+CD25+ cells) were particularly significant in group A. Moreover, an increase in protein concentrations, hypoalbuminemia and a polyclonal hypergammaglobulinemia were observed. Five of ten M. haemofelis-infected cats subsequently cleared bacteremia without antibiotic treatment. In conclusion, the study suggests that a previous hemoplasma infection, even when the cat has ostensibly recovered, may influence subsequent infections, lead to an enhancement phenomenon and other differences in infection kinetics.

Species differentiation of scutacarid mites (Heterostigmatina) using multivariate morphometric methods.

The genera of the mite family Scutacaridae (Heterostigmatina) can be easily distinguished by certain qualitative traits, whereas the species of these genera are lacking conspicuous distinctive features and thus, species descriptions are often based on quantitative characters. However, the intraspecific variability of these traits can be pronounced and the applicability of multivariate morphometric methods for species differentiation has not been studied so far. In the present study, four members of the genus Scutacarus, referred to as the acarorum species-complex, were analysed using traditional and geometric morphometric methods. The results showed that multivariate morphometric methods are perfectly suitable for differentiating even between morphologically similar scutacarid species, with traditional morphometrics performing better than geometric morphometrics. Despite their morphological similarity, morphometric analyses support the species status of the four members of the species-complex.

Hidden in the mangrove forest: the cryptic intertidal mite Carinozetes mangrovi sp. nov. (Acari, Oribatida, Selenoribatidae).

The small archipelago of Bermuda is a geologically young landmass in the Western Atlantic Ocean and recently turned out to be inhabited by a number of intertidal oribatid mites. One newly described species, Carinozetes bermudensis, showed an unusual vast range of habitats like sandy beaches, rocky substrate and mangroves. In the present study, 13 Bermudian populations of C. bermudensis were analysed to verify species integrity of specimens from different microhabitats. A morphometric analysis of 17 continuous variables as well as a molecular genetic investigation of the mitochondrial cytochrome oxidase subunit I revealed the existence of a new species Carinozetes mangrovi sp. nov., inhabiting exclusively intertidal algae growing on mangrove roots. Although both species are morphologically nearly identical, the configuration of the genus-specific ventral carinae represents a clear diagnostic character. The high genetic divergence of approximately 12 % of the cytochrome oxidase subunit I gene sequence between C. bermudensis and C. mangrovi sp. nov. suggests that these two species diverged before the emergence of the Bermuda islands. Accordingly, both of them are older than the geologically young archipelago of Bermuda.

Timut Pepper Extract Slows Age-Dependent Decline of Mobility and Collagen Loss and Promotes Longevity.

Investigations into human longevity are increasingly focusing on healthspan enhancement, not just lifespan extension. Lifestyle modifications and nutritional choices, including food supplements, can significantly affect aging and general health. Phytochemicals in centenarians' diets, such as those found in Timut pepper, a Nepalese spice with various medicinal properties, may contribute to their longevity. Similarly, Sichuan pepper, a related species, has demonstrated anti-inflammatory and neuroprotective activities. With the broader purpose of uncovering a novel treatment to address aging and its comorbidities, this study aims to investigate the potential lifespan- and healthspan-promoting effects of Timut pepper using the model organism Caenorhabditis elegans. We show that Timut pepper extract extends C. elegans' lifespan at different maintenance temperatures and increases the proportion of active nematodes in their early adulthood. In addition, we show that Timut pepper extract enhances speed and distance moved as the nematodes age. Finally, Timut pepper extract assures extracellular matrix homeostasis by slowing the age-dependent decline of collagen expression.

Methods for rearing scutacarid mites (Acari, Heterostigmatina) and the influence of laboratory cultures on morphometric variables.

Mites of the soil inhabiting family Scutacaridae (Heterostigmatina) are distributed throughout the world, but only rarely found in high densities. Larvae and males are extremely difficult to detect and identify in soil samples. Laboratory cultures are necessary to describe these life stages, detect female dimorphism, or carry out other kinds of biological study. The present paper gives an historical overview of the methods applied for rearing scutacarids, demonstrating that thus far the use of glass tubes stuffed with soil is the most valuable method. Morphometric comparisons between field collected and laboratory reared specimens of two scutacarid species, Scutacarus acarorum Goeze and Heterodispus foveatus Jagersbacher-Baumann and Ebermann, revealed a clear influence of environmental conditions on the phenotype of laboratory-reared mites. Size correction minimized the environmentally induced variation and should therefore be mandatory for classification of species based on morphometric variables. Taxonomic assignment of laboratory reared scutacarids is possible, but must be done with extreme caution.

Exploring the health and well-being of a national sample of U.K. treatment-seeking veterans.

OBJECTIVE: Military veterans experience a higher prevalence of mental health difficulties compared with the general population. Research has highlighted veterans who experience mental health difficulties have poorer treatment outcomes. Understanding veteran needs may help improve veteran mental health services and treatment outcomes. The aim of this study was to explore the complexity of health and well-being needs among a national clinical sample of veterans. METHOD: In total, 989 veterans from a U.K. veterans mental health charity were invited to complete a questionnaire about their sociodemographic characteristics, military experiences, physical and mental health, and well-being. RESULTS: Of the invitees, 428 veterans (43.3%) completed the questionnaire. Common mental disorders, such as anxiety and depression, were the most frequently reported mental health difficulty (80.7%), followed by loneliness (79.1%) and perceived low social support (72.2%). Rates of PTSD were also high (68.7% any PTSD), with most participants experiencing complex PTSD (CPTSD; 62.5%) compared with PTSD (6.2%). Veterans with co-occurring CPTSD symptoms have poorer health due to a higher number of comorbidities, for instance between CPTSD and moral injury. CONCLUSIONS: Comorbidity appeared to be the norm rather than the exception within treatment-seeking veterans. As such, it seems important for veteran mental health services to take a holistic approach when supporting veterans. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Self-control and performance while working from home.

This study explores the role of trait self-control in individuals' changes in performance and well-being when working from home (WFH). In a three-wave longitudinal study with UK workers in the midst of the COVID-19 pandemic, we find that low self-control workers experienced a significant positive adjustment to WFH over time: The number of reported work distractions decreased, and self-assessed performance increased over the period of four months. In contrast, high self-control individuals did not show a similar upward trajectory. Despite the positive adjustment of low self-control individuals over time, on average, self-control was still positively associated with performance and negatively associated with work distractions. However, trait self-control was not consistently associated with changes in well-being. These findings provide a more nuanced view on trait self-control, suggesting that low self-control individuals can improve initial performance over time when working from home.

A closer look reveals hidden diversity in the intertidal Caribbean Fortuyniidae (Acari, Oribatida).

A molecular genetic and morphometric investigation revealed the supposedly widespread Caribbean and Western Atlantic intertidal oribatid mite species Fortuynia atlantica to comprise at least two different species. Although there are no distinct morphological differences separating these taxa, COI and 18S sequence divergence data, as well as different species delimitation analyses, clearly identify the two species. Fortuynia atlantica is distributed in the northern Caribbean and the Western Atlantic and the new Fortuynia antillea sp. nov. is presently endemic to Barbados. Vicariance is supposed to be responsible for their genetic diversification and stabilizing selection caused by the extreme intertidal environment is suggested to be the reason for the found morphological stasis. The genetic structure of Fortuynia atlantica indicates that Bermudian populations are derived from the northern Caribbean and thus support the theory of dispersal by drifting on the Gulf Stream. Haplotype network data suggest that Bermudian and Bahamian populations were largely shaped by colonization, expansion and extinction events caused by dramatic sea level changes during the Pleistocene. A preliminary phylogenetic analysis based on 18S gene sequences indicates that the globally distributed genus Fortuynia may be a monophyletic group, whereas Caribbean and Western Atlantic members are distinctly separated from the Indo-Pacific and Western Pacific species.

Pericyte, but not astrocyte, hypoxia inducible factor-1 (HIF-1) drives hypoxia-induced vascular permeability in vivo.

BACKGROUND: Ways to prevent disease-induced vascular modifications that accelerate brain damage remain largely elusive. Improved understanding of perivascular cell signalling could provide unparalleled insight as these cells impact vascular stability and functionality of the neurovascular unit as a whole. Identifying key drivers of astrocyte and pericyte responses that modify cell-cell interactions and crosstalk during injury is key. At the cellular level, injury-induced outcomes are closely entwined with activation of the hypoxia-inducible factor-1 (HIF-1) pathway. Studies clearly suggest that endothelial HIF-1 signalling increases blood-brain barrier permeability but the influence of perivascular HIF-1 induction on outcome is unknown. Using novel mouse lines with astrocyte and pericyte targeted HIF-1 loss of function, we herein show that vascular stability in vivo is differentially impacted by perivascular hypoxia-induced HIF-1 stabilization. METHODS: To facilitate HIF-1 deletion in adult mice without developmental complications, novel Cre-inducible astrocyte-targeted (GFAP-CreERT2; HIF-1αfl/fl and GLAST-CreERT2; HIF-1αfl/fl) and pericyte-targeted (SMMHC-CreERT2; HIF-1αfl/fl) transgenic animals were generated. Mice in their home cages were exposed to either normoxia (21% O2) or hypoxia (8% O2) for 96 h in an oxygen-controlled humidified glove box. All lines were similarly responsive to hypoxic challenge and post-Cre activation showed significantly reduced HIF-1 target gene levels in the individual cells as predicted. RESULTS: Unexpectedly, hypoxia-induced vascular remodelling was unaffected by HIF-1 loss of function in the two astrocyte lines but effectively blocked in the pericyte line. In correlation, hypoxia-induced barrier permeability and water accumulation were abrogated only in pericyte targeted HIF-1 loss of function mice. In contrast to expectation, brain and serum levels of hypoxia-induced VEGF, TGF-ß and MMPs (genes known to mediate vascular remodelling) were unaffected by HIF-1 deletion in all lines. However, in agreement with the permeability data, immunofluorescence and electron microscopy showed clear prevention of hypoxia-induced tight junction disruption in the pericyte loss of function line. CONCLUSION: This study shows that pericyte but not astrocyte HIF-1 stabilization modulates endothelial tight junction functionality and thereby plays a pivotal role in hypoxia-induced vascular dysfunction. Whether the cells respond similarly or differentially to other injury stimuli will be of significant relevance.