Naive T lymphocytes chemotax long distance to CCL21 but not to a source of bioactive S1P

Naive T lymphocytes traffic through the organism in search for antigen, alternating between blood and secondary lymphoid organs. Lymphocyte homing to lymph nodes relies on CCL21 chemokine sensing by CCR7 receptors, while exit into efferent lymphatics relies on sphingolipid S1P sensing by S1PR1 receptors. While both molecules are claimed chemotactic, a quantitative analysis of naive T lymphocyte migration along defined gradients is missing. Here, we used a reductionist approach to study the real-time single-cell response of naive T lymphocytes to CCL21 and serum rich in bioactive S1P. Using microfluidic and micropatterning ad hoc tools, we show that CCL21 triggers stable polarization and long-range chemotaxis of cells, whereas S1P-rich serum triggers a transient polarization only and no significant displacement, potentially representing a brief transmigration step through exit portals. Our in vitro data thus suggest that naive T lymphocyte chemotax long distances to CCL21 but not toward a source of bioactive S1P

Living-floors and Structures from the Lower Palaeolithic to the Bronze Age in Italy

Summary report of the research carried out on the Living floors of the Palaeolithic to Neolithic periods in many prehistoric sites of northern Ital

Guillain-Barré syndrome and COVID-19: an observational multicentre study from two Italian hotspot regions

Objective: Single cases and small series of Guillain-Barré syndrome (GBS) have been reported during the SARS-CoV-2 outbreak worldwide. We evaluated incidence and clinical features of GBS in a cohort of patients from two regions of northern Italy with the highest number of patients with COVID-19. Methods: GBS cases diagnosed in 12 referral hospitals from Lombardy and Veneto in March and April 2020 were retrospectively collected. As a control population, GBS diagnosed in March and April 2019 in the same hospitals were considered. Results: Incidence of GBS in March and April 2020 was 0.202/100 000/month (estimated rate 2.43/100 000/year) vs 0.077/100 000/month (estimated rate 0.93/100 000/year) in the same months of 2019 with a 2.6-fold increase. Estimated incidence of GBS in COVID-19-positive patients was 47.9/100 000 and in the COVID-19-positive hospitalised patients was 236/100 000. COVID-19-positive patients with GBS, when compared with COVID-19-negative subjects, showed lower MRC sum score (26.3±18.3 vs 41.4±14.8, p=0.006), higher frequency of demyelinating subtype (76.6% vs 35.3%, p=0.011), more frequent low blood pressure (50% vs 11.8%, p=0.017) and higher rate of admission to intensive care unit (66.6% vs 17.6%, p=0.002). Conclusions: This study shows an increased incidence of GBS during the COVID-19 outbreak in northern Italy, supporting a pathogenic link. COVID-19-associated GBS is predominantly demyelinating and seems to be more severe than non-COVID-19 GBS, although it is likely that in some patients the systemic impairment due to COVID-19 might have contributed to the severity of the whole clinical picture

Weight and metabolic effects of cpap in obstructive sleep apnea patients with obesity

<p>Abstract</p> <p>Background</p> <p>Obstructive sleep apnea (OSA) is associated with obesity, insulin resistance (IR) and diabetes. Continuous positive airway pressure (CPAP) rapidly mitigates OSA in obese subjects but its metabolic effects are not well-characterized. We postulated that CPAP will decrease IR, ghrelin and resistin and increase adiponectin levels in this setting.</p> <p>Methods</p> <p>In a pre- and post-treatment, within-subject design, insulin and appetite-regulating hormones were assayed in 20 obese subjects with OSA before and after 6 months of CPAP use. Primary outcome measures included glucose, insulin, and IR levels. Other measures included ghrelin, leptin, adiponectin and resistin levels. Body weight change were recorded and used to examine the relationship between glucose regulation and appetite-regulating hormones.</p> <p>Results</p> <p>CPAP effectively improved hypoxia. However, subjects had increased insulin and IR. Fasting ghrelin decreased significantly while leptin, adiponectin and resistin remained unchanged. Forty percent of patients gained weight significantly. Changes in body weight directly correlated with changes in insulin and IR. Ghrelin changes inversely correlated with changes in IR but did not change as a function of weight.</p> <p>Conclusions</p> <p>Weight change rather than elimination of hypoxia modulated alterations in IR in obese patients with OSA during the first six months of CPAP therapy.</p

Polymorphisms of genes coding for ghrelin and its receptor in relation to colorectal cancer risk: a two-step gene-wide case-control study

<p>Abstract</p> <p>Background</p> <p>Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), has two major functions: the stimulation of the growth hormone production and the stimulation of food intake. Accumulating evidence also indicates a role of ghrelin in cancer development.</p> <p>Methods</p> <p>We conducted a case-control study to examine the association of common genetic variants in the genes coding for ghrelin (GHRL) and its receptor (GHSR) with colorectal cancer risk. Pairwise tagging was used to select the 11 polymorphisms included in the study. The selected polymorphisms were genotyped in 680 cases and 593 controls from the Czech Republic.</p> <p>Results</p> <p>We found two SNPs associated with lower risk of colorectal cancer, namely SNPs rs27647 and rs35683. We replicated the two hits, in additional 569 cases and 726 controls from Germany.</p> <p>Conclusion</p> <p>A joint analysis of the two populations indicated that the T allele of rs27647 SNP exerted a protective borderline effect (P_trend= 0.004).</p

Cognitive and cognitive-motor interventions affecting physical functioning: A systematic review

Background Several types of cognitive or combined cognitive-motor intervention types that might influence physical functions have been proposed in the past: training of dual-tasking abilities, and improving cognitive function through behavioral interventions or the use of computer games. The objective of this systematic review was to examine the literature regarding the use of cognitive and cognitive-motor interventions to improve physical functioning in older adults or people with neurological impairments that are similar to cognitive impairments seen in aging. The aim was to identify potentially promising methods that might be used in future intervention type studies for older adults. Methods A systematic search was conducted for the Medline/Premedline, PsycINFO, CINAHL and EMBASE databases. The search was focused on older adults over the age of 65. To increase the number of articles for review, we also included those discussing adult patients with neurological impairments due to trauma, as these cognitive impairments are similar to those seen in the aging population. The search was restricted to English, German and French language literature without any limitation of publication date or restriction by study design. Cognitive or cognitive-motor interventions were defined as dual-tasking, virtual reality exercise, cognitive exercise, or a combination of these. Results 28 articles met our inclusion criteria. Three articles used an isolated cognitive rehabilitation intervention, seven articles used a dual-task intervention and 19 applied a computerized intervention. There is evidence to suggest that cognitive or motor-cognitive methods positively affects physical functioning, such as postural control, walking abilities and general functions of the upper and lower extremities, respectively. The majority of the included studies resulted in improvements of the assessed functional outcome measures. Conclusions The current evidence on the effectiveness of cognitive or motor-cognitive interventions to improve physical functioning in older adults or people with neurological impairments is limited. The heterogeneity of the studies published so far does not allow defining the training methodology with the greatest effectiveness. This review nevertheless provides important foundational information in order to encourage further development of novel cognitive or cognitive-motor interventions, preferably with a randomized control design. Future research that aims to examine the relation between improvements in cognitive skills and the translation to better performance on selected physical tasks should explicitly take the relation between the cognitive and physical skills into account.ISSN:1471-231

Sex, Ecology and the Brain: Evolutionary Correlates of Brain Structure Volumes in Tanganyikan Cichlids

Analyses of the macroevolutionary correlates of brain structure volumes allow pinpointing of selective pressures influencing specific structures. Here we use a multiple regression framework, including phylogenetic information, to analyze brain structure evolution in 43 Tanganyikan cichlid species. We analyzed the effect of ecological and sexually selected traits for species averages, the effect of ecological traits for each sex separately and the influence of sexual selection on structure dimorphism. Our results indicate that both ecological and sexually selected traits have influenced brain structure evolution. The patterns observed in males and females generally followed those observed at the species level. Interestingly, our results suggest that strong sexual selection is associated with reduced structure volumes, since all correlations between sexually selected traits and structure volumes were negative and the only statistically significant association between sexual selection and structure dimorphism was also negative. Finally, we previously found that monoparental female care was associated with increased brain size. However, here cerebellum and hypothalamus volumes, after controlling for brain size, associated negatively with female-only care. Thus, in accord with the mosaic model of brain evolution, brain structure volumes may not respond proportionately to changes in brain size. Indeed selection favoring larger brains can simultaneously lead to a reduction in relative structure volumes

Unacylated Ghrelin Rapidly Modulates Lipogenic and Insulin Signaling Pathway Gene Expression in Metabolically Active Tissues of GHSR Deleted Mice

Background: There is increasing evidence that unacylated ghrelin (UAG) improves insulin sensitivity and glucose homeostasis; however, the mechanism for this activity is not fully understood since a UAG receptor has not been discovered. Methodology/Principal Findings: To assess potential mechanisms of UAG action in vivo, we examined rapid effects of UAG on genome-wide expression patterns in fat, muscle and liver of growth hormone secretagogue receptor (GHSR)-ablated mice using microarrays. Expression data were analyzed using Ingenuity Pathways Analysis and Gene Set Enrichment Analysis. Regulation of subsets of these genes was verified by quantitative PCR in an independent experiment. UAG acutely regulated clusters of genes involved in glucose and lipid metabolism in all three tissues, consistent with enhancement of insulin sensitivity. Conclusions/Significance: Fat, muscle and liver are central to the control of lipid and glucose homeostasis. UAG rapidly modulates the expression of metabolically important genes in these tissues in GHSR-deleted mice indicating a direct, GHSRindependent, action of UAG to improve insulin sensitivity and metabolic profile

Ghrelin Indirectly Activates Hypophysiotropic CRF Neurons in Rodents

Ghrelin is a stomach-derived hormone that regulates food intake and neuroendocrine function by acting on its receptor, GHSR (Growth Hormone Secretagogue Receptor). Recent evidence indicates that a key function of ghrelin is to signal stress to the brain. It has been suggested that one of the potential stress-related ghrelin targets is the CRF (Corticotropin-Releasing Factor)-producing neurons of the hypothalamic paraventricular nucleus, which secrete the CRF neuropeptide into the median eminence and activate the hypothalamic-pituitary-adrenal axis. However, the neural circuits that mediate the ghrelin-induced activation of this neuroendocrine axis are mostly uncharacterized. In the current study, we characterized in vivo the mechanism by which ghrelin activates the hypophysiotropic CRF neurons in mice. We found that peripheral or intra-cerebro-ventricular administration of ghrelin strongly activates c-fos – a marker of cellular activation – in CRF-producing neurons. Also, ghrelin activates CRF gene expression in the paraventricular nucleus of the hypothalamus and the hypothalamic-pituitary-adrenal axis at peripheral level. Ghrelin administration directly into the paraventricular nucleus of the hypothalamus also induces c-fos within the CRF-producing neurons and the hypothalamic-pituitary-adrenal axis, without any significant effect on the food intake. Interestingly, dual-label immunohistochemical analysis and ghrelin binding studies failed to show GHSR expression in CRF neurons. Thus, we conclude that ghrelin activates hypophysiotropic CRF neurons, albeit indirectly