Calcium and Vitamin D increase mRNA levels for the growth control hIK1 channel in human epidermal keratinocytes but functional channels are not observed

BACKGROUND: Intermediate-conductance, calcium-activated potassium channels (IKs) modulate proliferation and differentiation in mesodermal cells by enhancing calcium influx, and they contribute to the physiology of fluid movement in certain epithelia. Previous reports suggest that IK channels stimulate proliferative growth in a keratinocyte cell line; however, because these channels indirectly promote calcium influx, a critically unique component of the keratinocyte differentiation program, an alternative hypothesis is that they would be anti-proliferative and pro-differentiating. This study addresses these hypotheses. METHODS: Real-time PCR, patch clamp electrophysiology, and proliferation assays were used to determine if human IK1 (hIK1) expression and function are correlated with either proliferation or differentiation in cultured human skin epidermal keratinocytes, and skin biopsies grown in explant culture. RESULTS: hIK1 mRNA expression in human keratinocytes and skin was increased in response to anti-proliferative/pro-differentiating stimuli (elevated calcium and Vitamin D). Correspondingly, the hIK1 agonist 1-EBIO inhibited keratinocyte proliferation suggesting that the channel could be anti-proliferative and pro-differentiating. However, this proliferative inhibition by 1-EBIO was not reversed by a panel of hIK1 blockers, calling into question the mechanism of 1-EBIO action. Subsequent patch clamp electrophysiological analysis failed to detect hIK1 channel currents in keratinocytes, even those expressing substantial hIK1 mRNA in response to calcium and Vitamin D induced differentiation. Identical electrophysiological recording conditions were then used to observe robust IK1 currents in fibroblasts which express IK1 mRNA levels comparable to those of keratinocytes. Thus, the absence of observable hIK1 currents in keratinocytes was not a function of the electrophysiological techniques. CONCLUSION: Human keratinocyte differentiation is stimulated by calcium mobilization and influx, and differentiation stimuli coordinately upregulate mRNA levels of the calcium-activated hIK1 channel. This upregulation is paradoxical in that functional hIK1 channels are not observed in cultured keratinocytes. It appears, therefore, that hIK1 does not contribute to the functional electrophysiology of primary human keratinocytes, nor intact human skin. Further, the results indicate caution is required when interpreting experiments utilizing pharmacological hIK1 modulators in human keratinocytes

Fifty-Year Fate and Impact of General Medical Journals

Background: Influential medical journals shape medical science and practice and their prestige is usually appraised by citation impact metrics, such as the journal impact factor. However, how permanent are medical journals and how stable is their impact over time? Methods and Results: We evaluated what happened to general medical journals that were publishing papers half a century ago, in 1959. Data were retrieved from ISI Web of Science for citations and PubMed (Journals function) for journal history. Of 27 eligible journals publishing in 1959, 4 have stopped circulation (including two of the most prestigious journals in 1959) and another 7 changed name between 1959 and 2009. Only 6 of these 27 journals have been published continuously with their initial name since they started circulation. The citation impact of papers published in 1959 gives a very different picture from the current journal impact factor; the correlation between the two is non-significant and very close to zero. Only 13 of the 5,223 papers published in 1959 received at least 5 citations in 2009. Conclusions: Journals are more permanent entities than single papers, but they are also subject to major change and their relative prominence can change markedly over time

Does the mind map learning strategy facilitate information retrieval and critical thinking in medical students?

<p>Abstract</p> <p>Background</p> <p>A learning strategy underutilized in medical education is mind mapping. Mind maps are multi-sensory tools that may help medical students organize, integrate, and retain information. Recent work suggests that using mind mapping as a note-taking strategy facilitates critical thinking. The purpose of this study was to investigate whether a relationship existed between mind mapping and critical thinking, as measured by the Health Sciences Reasoning Test (HSRT), and whether a relationship existed between mind mapping and recall of domain-based information.</p> <p>Methods</p> <p>In this quasi-experimental study, 131 first-year medical students were randomly assigned to a standard note-taking (SNT) group or mind map (MM) group during orientation. Subjects were given a demographic survey and pre-HSRT. They were then given an unfamiliar text passage, a pre-quiz based upon the passage, and a 30-minute break, during which time subjects in the MM group were given a presentation on mind mapping. After the break, subjects were given the same passage and wrote notes based on their group (SNT or MM) assignment. A post-quiz based upon the passage was administered, followed by a post-HSRT. Differences in mean pre- and post-quiz scores between groups were analyzed using independent samples <it>t</it>-tests, whereas differences in mean pre- and post-HSRT total scores and subscores between groups were analyzed using ANOVA. Mind map depth was assessed using the Mind Map Assessment Rubric (MMAR).</p> <p>Results</p> <p>There were no significant differences in mean scores on both the pre- and post-quizzes between note-taking groups. And, no significant differences were found between pre- and post-HSRT mean total scores and subscores.</p> <p>Conclusions</p> <p>Although mind mapping was not found to increase short-term recall of domain-based information or critical thinking compared to SNT, a brief introduction to mind mapping allowed novice MM subjects to perform similarly to SNT subjects. This demonstrates that medical students using mind maps can successfully retrieve information in the short term, and does not put them at a disadvantage compared to SNT students. Future studies should explore longitudinal effects of mind-map proficiency training on both short- and long-term information retrieval and critical thinking.</p

Mitochondrial phylogeography of baboons (Papio spp.) – Indication for introgressive hybridization?

<p>Abstract</p> <p>Background</p> <p>Baboons of the genus <it>Papio </it>are distributed over wide ranges of Africa and even colonized parts of the Arabian Peninsula. Traditionally, five phenotypically distinct species are recognized, but recent molecular studies were not able to resolve their phylogenetic relationships. Moreover, these studies revealed para- and polyphyletic (hereafter paraphyletic) mitochondrial clades for baboons from eastern Africa, and it was hypothesized that introgressive hybridization might have contributed substantially to their evolutionary history. To further elucidate the phylogenetic relationships among baboons, we extended earlier studies by analysing the complete mitochondrial cytochrome <it>b </it>gene and the 'Brown region' from 67 specimens collected at 53 sites, which represent all species and which cover most of the baboons' range.</p> <p>Results</p> <p>Based on phylogenetic tree reconstructions seven well supported major haplogroups were detected, which reflect geographic populations and discordance between mitochondrial phylogeny and baboon morphology. Our divergence age estimates indicate an initial separation into southern and northern baboon clades 2.09 (1.54–2.71) million years ago (mya). We found deep divergences between haplogroups within several species (~2 mya, northern and southern yellow baboons, western and eastern olive baboons and northern and southern chacma baboons), but also recent divergence ages among species (< 0.7 mya, yellow, olive and hamadryas baboons in eastern Africa).</p> <p>Conclusion</p> <p>Our study confirms earlier findings for eastern Africa, but shows that baboon species from other parts of the continent are also mitochondrially paraphyletic. The phylogenetic patterns suggest a complex evolutionary history with multiple phases of isolation and reconnection of populations. Most likely all these biogeographic events were triggered by multiple cycles of expansion and retreat of savannah biomes during Pleistocene glacial and inter-glacial periods. During contact phases of populations reticulate events (i.e. introgressive hybridization) were highly likely, similar to ongoing hybridization, which is observed between East African baboon populations. Defining the extent of the introgressive hybridization will require further molecular studies that incorporate additional sampling sites and nuclear loci.</p

Demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy: an international cohort study and individual participant data meta-analysis

Background: Posterior cortical atrophy is a rare syndrome characterised by early, prominent, and progressive impairment in visuoperceptual and visuospatial processing. The disorder has been associated with underlying neuropathological features of Alzheimer's disease, but large-scale biomarker and neuropathological studies are scarce. We aimed to describe demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy in a large international cohort.// Methods: We searched PubMed between database inception and Aug 1, 2021, for all published research studies on posterior cortical atrophy and related terms. We identified research centres from these studies and requested deidentified, individual participant data (published and unpublished) that had been obtained at the first diagnostic visit from the corresponding authors of the studies or heads of the research centres. Inclusion criteria were a clinical diagnosis of posterior cortical atrophy as defined by the local centre and availability of Alzheimer's disease biomarkers (PET or CSF), or a diagnosis made at autopsy. Not all individuals with posterior cortical atrophy fulfilled consensus criteria, being diagnosed using centre-specific procedures or before development of consensus criteria. We obtained demographic, clinical, biofluid, neuroimaging, and neuropathological data. Mean values for continuous variables were combined using the inverse variance meta-analysis method; only research centres with more than one participant for a variable were included. Pooled proportions were calculated for binary variables using a restricted maximum likelihood model. Heterogeneity was quantified using I2.// Findings: We identified 55 research centres from 1353 papers, with 29 centres responding to our request. An additional seven centres were recruited by advertising via the Alzheimer's Association. We obtained data for 1092 individuals who were evaluated at 36 research centres in 16 countries, the other sites having not responded to our initial invitation to participate to the study. Mean age at symptom onset was 59·4 years (95% CI 58·9–59·8; I2=77%), 60% (56–64; I2=35%) were women, and 80% (72–89; I2=98%) presented with posterior cortical atrophy pure syndrome. Amyloid β in CSF (536 participants from 28 centres) was positive in 81% (95% CI 75–87; I2=78%), whereas phosphorylated tau in CSF (503 participants from 29 centres) was positive in 65% (56–75; I2=87%). Amyloid-PET (299 participants from 24 centres) was positive in 94% (95% CI 90–97; I2=15%), whereas tau-PET (170 participants from 13 centres) was positive in 97% (93–100; I2=12%). At autopsy (145 participants from 13 centres), the most frequent neuropathological diagnosis was Alzheimer's disease (94%, 95% CI 90–97; I2=0%), with common co-pathologies of cerebral amyloid angiopathy (71%, 54–88; I2=89%), Lewy body disease (44%, 25–62; I2=77%), and cerebrovascular injury (42%, 24–60; I2=88%).// Interpretation: These data indicate that posterior cortical atrophy typically presents as a pure, young-onset dementia syndrome that is highly specific for underlying Alzheimer's disease pathology. Further work is needed to understand what drives cognitive vulnerability and progression rates by investigating the contribution of sex, genetics, premorbid cognitive strengths and weaknesses, and brain network integrity

Cyanobacterial lipopolysaccharides and human health – a review

Cyanobacterial lipopolysaccharide/s (LPS) are frequently cited in the cyanobacteria literature as toxins responsible for a variety of heath effects in humans, from skin rashes to gastrointestinal, respiratory and allergic reactions. The attribution of toxic properties to cyanobacterial LPS dates from the 1970s, when it was thought that lipid A, the toxic moiety of LPS, was structurally and functionally conserved across all Gram-negative bacteria. However, more recent research has shown that this is not the case, and lipid A structures are now known to be very different, expressing properties ranging from LPS agonists, through weak endotoxicity to LPS antagonists. Although cyanobacterial LPS is widely cited as a putative toxin, most of the small number of formal research reports describe cyanobacterial LPS as weakly toxic compared to LPS from the Enterobacteriaceae. We systematically reviewed the literature on cyanobacterial LPS, and also examined the much lager body of literature relating to heterotrophic bacterial LPS and the atypical lipid A structures of some photosynthetic bacteria. While the literature on the biological activity of heterotrophic bacterial LPS is overwhelmingly large and therefore difficult to review for the purposes of exclusion, we were unable to find a convincing body of evidence to suggest that heterotrophic bacterial LPS, in the absence of other virulence factors, is responsible for acute gastrointestinal, dermatological or allergic reactions via natural exposure routes in humans. There is a danger that initial speculation about cyanobacterial LPS may evolve into orthodoxy without basis in research findings. No cyanobacterial lipid A structures have been described and published to date, so a recommendation is made that cyanobacteriologists should not continue to attribute such a diverse range of clinical symptoms to cyanobacterial LPS without research confirmation

Distribution and movement of domestic rainbow trout, Oncorhynchus mykiss, during pulsed flows in the South Fork American River, California

We tracked the movements of ten small (SL = 25.5–31.0 cm) and ten large (SL = 32.0–38.5 cm) radio-tagged domestic rainbow trout (Oncorhynchus mykiss) in response to frequent pulsed releases of water in the South Fork American River (California) from July to October 2005. In week one all the small trout moved less than 1 km upstream or downstream of their release sites. Four small trout moved 1–3 km upstream or downstream of their release sites in the following 8 weeks. Seven out of ten large trout moved downstream after their release. In subsequent weeks most large trout showed smaller upstream and downstream movements, and were observed between 1 km upstream and 8 km downstream of their release sites. Our results suggest that domestic rainbow trout with SL &gt; 25 cm are not forced downstream by daily pulsed flow increases from 5 to over 40 m3s−1