Surfing on the seascape:adaptation in a changing environment

The environment changes constantly at various time scales and, in order to survive, species need to keep adapting. Whether these species succeed in avoiding extinction is a major evolutionary question. Using a multilocus evolutionary model of a mutation‐limited population adapting under strong selection, we investigate the effects of the frequency of environmental fluctuations on adaptation. Our results rely on an “adaptive‐walk” approximation and use mathematical methods from evolutionary computation theory to investigate the interplay between fluctuation frequency, the similarity of environments, and the number of loci contributing to adaptation. First, we assume a linear additive fitness function, but later generalize our results to include several types of epistasis. We show that frequent environmental changes prevent populations from reaching a fitness peak, but they may also prevent the large fitness loss that occurs after a single environmental change. Thus, the population can survive, although not thrive, in a wide range of conditions. Furthermore, we show that in a frequently changing environment, the similarity of threats that a population faces affects the level of adaptation that it is able to achieve. We check and supplement our analytical results with simulations

5-HT obesity medication efficacy via POMC activation is maintained during aging

Peer reviewedPublisher PD

“Late Hallstatt” hillforts in the Western Carpathians : new contribution to an old discussion

The article presents new research on fortified settlements from the Early Iron Age in the Orava and Dunajec river valleys. Based on the characteristics of the construction of the fortifications and similarities in terms of material culture, we propose recognizing the hillforts discovered here as a manifestation of one cultural and settlement horizon related to the so-called Pre-Púchov stage. The radiocarbon determinations obtained for the contexts stratigraphically related to the ramparts from the Nižná-Ostražica, Zabrzeż-Babia Góra, and Maszkowice-Góra Zyndrama sites are already located on the calibration curve after the so-called Hallstatt plateau and allow this horizon to be dated to the 4th century BC, i.e. to the times corresponding to the La Tène B1–B2 phases. Our observations confirm the opinions appearing in more recent literature about the need to date the Pre-Púchov stage in Slovakia earlier, and discuss the thesis about the continuation of settlement at the beginning of the La Tène period. With regard to the Polish Carpathian zone, arguments indicating the possibility of the survival of settlements with Early Iron Age traditions up to the 4th century BC are presented for the first time. This allows us to assume that the process of the formation of the cultural tradition of the La Tène period here progressed in a similar manner to Slovakia, and it was not solely the result of migration from the latter.Príspevok prezentuje nové výskumy na opevnených sídliskách z doby halštatskej v doline Oravy a Dunajca. Na základe charakteristiky výstavby opevnení a podobností z pohľadu hmotnej kultúry, považujeme prezentované hradiská za prejav jedného kultúrneho a sídliskového horizontu (tzv. predpúchovský horizont). Analyzované radiokarbónové vzorky získané z kontextov stratigraficky súvisiacych s valmi z lokalít Nižná-Ostražica, Zabrzeż-Babia Góra a Maszkowice-Góra Zyndrama, sa nachádzajú na kalibračnej krivke už po tzv. halštatskom plató a umožňujú tento horizont datovať. do 4. storočia pred Kristom, teda do čias zodpovedajúcich laténskej fáze LT B1–B2. Výsledky potvrdzujú názory objavujúce sa v novšej literatúre o potrebe skoršieho datovania predpúchovského horizontu na Slovensku a tiež o pokračovaní osídlenia na začiatku doby laténskej. V súvislosti s karpatskou oblasťou na území Poľska sú po prvýkrát prezentované argumenty naznačujúce možnosť prežívania osád s tradíciami v staršej doby železnej až do 4. storočia pred Kristom. To umožňuje predpokladať, že proces formovania kultúrnej tradície doby laténskej tu prebiehal podobne ako na Slovensku a nebol len dôsledkom neskoršej migrácie.The article presents new research on fortified settlements from the Early Iron Age in the Orava and Dunajec river valleys. Based on the characteristics of the construction of the fortifications and similarities in terms of material culture, we propose recognizing the hillforts discovered here as a manifestation of one cultural and settlement horizon related to the so-called Pre-Púchov stage. The radiocarbon determinations obtained for the contexts stratigraphically related to the ramparts from the Nižná-Ostražica, Zabrzeż-Babia Góra, and Maszkowice-Góra Zyndrama sites are already located on the calibration curve after the so-called Hallstatt plateau and allow this horizon to be dated to the 4th century BC, i.e. to the times corresponding to the La Tène B1–B2 phases. Our observations confirm the opinions appearing in more recent literature about the need to date the Pre-Púchov stage in Slovakia earlier, and discuss the thesis about the continuation of settlement at the beginning of the La Tène period. With regard to the Polish Carpathian zone, arguments indicating the possibility of the survival of settlements with Early Iron Age traditions up to the 4th century BC are presented for the first time. This allows us to assume that the process of the formation of the cultural tradition of the La Tène period here progressed in a similar manner to Slovakia, and it was not solely the result of migration from the latter

Students of Color and COVID-19: Experiences, Coping Strategies, and Supports

The coronavirus disease of 2019, known as the COVID-19 pandemic, is a disaster event that posed significant physical, social, financial, and mental health risks to college students. Disproportionate experiences of stressors position students of color as a population particularly vulnerable to the negative impacts of COVID-19, thus, the current study assessed the impact of COVID-19 on undergraduate students of color in the United States. Students participated in semi-structured in-depth interviews about their experiences with stressors during the pandemic. Data were analyzed using conventional content analysis and revealed themes including (a) the pandemic’s impact on students; (b) basic needs as college students; (c) strategies used to cope with stressors; and (d) supports desired from institutions and faculty. Findings inform colleges and healthcare providers of the most salient concerns for students of color and the sources found helpful. As such, these findings may guide effective prevention and intervention strategies to minimize the effects of future disasters

5-HT2C Receptor Agonist Anorectic Efficacy Potentiated by 5-HT1B Receptor Agonist Coapplication: An Effect Mediated via Increased Proportion of Pro-Opiomelanocortin Neurons Activated

An essential component of the neural network regulating ingestive behavior is the brain 5-hydroxytryptamine2C receptor (5-HT2CR), agonists of which suppress food intake and were recently approved for obesity treatment by the US Food and Drug Administration. 5-HT2CR-regulated appetite is mediated primarily through activation of hypothalamic arcuate nucleus (ARC) pro-opiomelanocortin (POMC) neurons, which are also disinhibited through a 5-HT1BR-mediated suppression of local inhibitory inputs. Here we investigated whether 5-HT2CR agonist anorectic potency could be significantly enhanced by coadministration of a 5-HT1BR agonist and whether this was associated with augmented POMC neuron activation on the population and/or single-cell level. The combined administration of subanorectic concentrations of 5-HT2CR and 5-HT1BR agonists produced a 45% reduction in food intake and significantly greater in vivo ARC neuron activation in mice. The chemical phenotype of activated ARC neurons was assessed by monitoring agonist-induced cellular activity via calcium imaging in mouse POMC-EGFP brain slices, which revealed that combined agonists activated significantly more POMC neurons (46%) compared with either drug alone (~25% each). Single-cell electrophysiological analysis demonstrated that 5-HT2CR/5-HT1BR agonist coadministration did not significantly potentiate the firing frequency of individual ARC POMC-EGFP cells compared with agonists alone. These data indicate a functional heterogeneity ofARCPOMCneurons by revealing distinct subpopulations of POMC cells activated by 5-HT2CRs and disinhibited by 5-HT1BRs. Therefore, coadministration of a 5-HT1BR agonist potentiates the anorectic efficacy of 5-HT2CR compounds by increasing the number, but not the magnitude, of activated ARC POMC neurons and is of therapeutic relevance to obesity treatment. © 2013 the authors

A versatile and customizable low-cost 3D-printed open standard for microscopic imaging

Modern microscopes used for biological imaging often present themselves as black boxes whose precise operating principle remains unknown, and whose optical resolution and price seem to be in inverse proportion to each other. With UC2 (You. See. Too.) we present a low-cost, 3D-printed, open-source, modular microscopy toolbox and demonstrate its versatility by realizing a complete microscope development cycle from concept to experimental phase. The self-contained incubator-enclosed brightfield microscope monitors monocyte to macrophage cell differentiation for seven days at cellular resolution level (e.g. 2 μm). Furthermore, by including very few additional components, the geometry is transferred into a 400 Euro light sheet fluorescence microscope for volumetric observations of a transgenic Zebrafish expressing green fluorescent protein (GFP). With this, we aim to establish an open standard in optics to facilitate interfacing with various complementary platforms. By making the content and comprehensive documentation publicly available, the systems presented here lend themselves to easy and straightforward replications, modifications, and extensions

Information and Risk Modification Trial (INFORM): design of a randomised controlled trial of communicating different types of information about coronary heart disease risk, alongside lifestyle advice, to achieve change in health-related behaviour

Abstract Background Cardiovascular disease (CVD) remains the leading cause of death globally. Primary prevention of CVD requires cost-effective strategies to identify individuals at high risk in order to help target preventive interventions. An integral part of this approach is the use of CVD risk scores. Limitations in previous studies have prevented reliable inference about the potential advantages and the potential harms of using CVD risk scores as part of preventive strategies. We aim to evaluate short-term effects of providing different types of information about coronary heart disease (CHD) risk, alongside lifestyle advice, on health-related behaviours. Methods/Design In a parallel-group, open randomised trial, we are allocating 932 male and female blood donors with no previous history of CVD aged 40–84 years in England to either no intervention (control group) or to one of three active intervention groups: i) lifestyle advice only; ii) lifestyle advice plus information on estimated 10-year CHD risk based on phenotypic characteristics; and iii) lifestyle advice plus information on estimated 10-year CHD risk based on phenotypic and genetic characteristics. The primary outcome is change in objectively measured physical activity. Secondary outcomes include: objectively measured dietary behaviours; cardiovascular risk factors; current medication and healthcare usage; perceived risk; cognitive evaluation of provision of CHD risk scores; and psychological outcomes. The follow-up assessment takes place 12 weeks after randomisation. The experiences, attitudes and concerns of a subset of participants will be also studied using individual interviews and focus groups. Discussion The INFORM study has been designed to provide robust findings about the short-term effects of providing different types of information on estimated 10-year CHD risk and lifestyle advice on health-related behaviours. Trial registration Current Controlled Trials ISRCTN17721237 . Registered 12 January 2015

Author Correction: Effect of carnosine supplementation on the plasma lipidome in overweight and obese adults: a pilot randomised controlled trial

This is a corrigendum for the article of the same title, published in Scientific Reports (2017) 7/1 https://doi.org/10.1038/s41598-017-17577-

Associations of Vitamin D with Inter- and Intra-Muscular Adipose Tissue and Insulin Resistance in Women with and without Polycystic Ovary Syndrome

Low vitamin D and insulin resistance are common in polycystic ovary syndrome (PCOS) and associated with higher inter- and intra-muscular adipose tissue (IMAT). We investigated associations between vitamin D, IMAT and insulin resistance in a cross-sectional study of 40 women with PCOS and 30 women without PCOS, and pre- and post-exercise in a 12-week intervention in 16 overweight participants (10 with PCOS and six without PCOS). A non-classical body mass index (BMI) threshold was used to differentiate lean and overweight women (BMI ≥ 27 kg/m²). Measurements included plasma 25-hydroxyvitamin D (25OHD), insulin resistance (glucose infusion rate (GIR; mg/m²/min), fasting glucose and insulin, and glycated haemoglobin), visceral fat, mid-thigh IMAT (computed tomography) and total body fat (dual-energy X-ray absorptiometry). Women with both PCOS and low 25OHD levels had the lowest GIR (all p < 0.05). Higher IMAT was associated with lower 25OHD (B = -3.95; 95% CI -6.86, -1.05) and GIR (B = -21.3; 95% CI -37.16, -5.44) in women with PCOS. Overweight women with pre-exercise 25OHD ≥30 nmol/L had significant increases in GIR, and decreases in total and visceral fat (all p < 0.044), but no associations were observed when stratified by PCOS status. Women with PCOS and low 25OHD levels have increased insulin resistance which may be partly explained by higher IMAT. Higher pre-training 25OHD levels may enhance exercise-induced changes in body composition and insulin resistance in overweight women

Human Galectins Induce Conversion of Dermal Fibroblasts into Myofibroblasts and Production of Extracellular Matrix: Potential Application in Tissue Engineering and Wound Repair

Members of the galectin family of endogenous lectins are potent adhesion/growth-regulatory effectors. Their multi-functionality opens possibilities for their use in bioapplications. We studied whether human galectins induce the conversion of human dermal fibroblasts into myofibroblasts (MFBs) and the production of a bioactive extracellular matrix scaffold is suitable for cell culture. Testing a panel of galectins of all three subgroups, including natural and engineered variants, we detected activity for the proto-type galectin-1 and galectin-7, the chimera-type galectin-3 and the tandem-repeat-type galectin-4. The activity of galectin-1 required the integrity of the carbohydrate recognition domain. It was independent of the presence of TGF-beta 1, but it yielded an additive effect. The resulting MFBs, relevant, for example, for tumor progression, generated a matrix scaffold rich in fibronectin and galectin-1 that supported keratinocyte culture without feeder cells. Of note, keratinocytes cultured on this substratum presented a stem-like cell phenotype with small size and keratin-19 expression. In vivo in rats, galectin-1 had a positive effect on skin wound closure 21 days after surgery. In conclusion, we describe the differential potential of certain human galectins to induce the conversion of dermal fibroblasts into MFBs and the generation of a bioactive cell culture substratum. Copyright (C) 2011 S. Karger AG, Base