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1. Populations that expand their range can undergo rapid evolutionary adaptation of life-history traits, dispersal behaviour, and adaptation to the local environment. Such adaptation may be aided or hindered by sexual reproduction, depending on the context. 2. However, few empirical and experimental studies have investigated the genetic basis of adaptive evolution during range expansions. Even less attention has been given to the question how sexual reproduction may modulate such adaptive evolution during range expansions. selleck inhibitor 3. We here studied genomic adaptation during experimental range expansions of the protist Tetrahymena thermophila in landscapes with a uniform environment or a pH gradient. Specifically, we investigated two aspects of genomic adaptation during range expansion. Firstly, we investigated adaptive genetic change in terms of the underlying numbers of allele frequency changes from standing genetic variation and de novo variants. We focused on how sexual reproduction may alter this adaptive geneti may have swamped expanding populations with maladapted alleles, thus reducing the extent of evolutionary adaptation during range expansion. Sexual reproduction also altered the genetic basis of adaptation in our evolving populations via de novo variants, possibly by purging deleterious mutations or by revealing fitness benefits of rare genetic variants.

Anaesthesia is required to assist the treatment of postpartum haemorrhage (PPH) when manual removal of the placenta or emptying of the uterine cavity is required. The choice between general or regional anaesthesia may depend upon factors such as existing epidural, airway, hypovolaemia, and tradition.

Data from a randomized controlled trial of PPH (FIB-PPH) was used to reveal differences between delivery centres. In addition, national data of 5,601 PPH procedures requiring anaesthesia during 2010-2015 was collected from the Danish Medical Birth Registry, the National Danish Patient Registry, and the Danish Anaesthesia Database. The aim is to describe the variation in choice of anaesthesia for treatment of PPH.

Data from the randomized trial showed large differences in practice between centres not explained by physiological factors. Using national Danish registry data, we show that large delivery centres as compared to small centres prefer regional anaesthesia for PPH procedures in opposed to general anaelated from literature on caesarean sections. Future studies should address the optimal choice of anaesthesia for PPH procedures.Generalized pruritus is common in chronic kidney disease (CKD) and requires investigation of all possible causes and treatment where possible1 . Specific to dialysis, >60% of patients are affected2 and almost half experience moderate to severe pruritus, which is associated with poor quality of life (QOL), reduced sleep, and death2 . Unfortunately, there are few approved therapies for CKD-associated pruritus and off-label treatments have limited efficacy. More recently, mu-opioid receptor antagonists (MORAs) and novel kappa-opioid receptor agonists (KORAs) have been investigated as possible therapies.

Understanding how drought and biomass allocation patterns influence competitive ability can help identify traits related to invasiveness and guide management. Vincetoxicum nigrum and V. rossicum are increasingly problematic herbaceous perennial vines in the northeastern United States and southeastern Canada.

Using a greenhouse experiment, we investigated how biomass allocation and competition intensity of Vincetoxicum spp. responded to four competitive regimes at two levels of soil water availability in the presence of conspecific or congeneric neighbors.

Soil moisture was the most important influence on growth and biomass allocation. Vincetoxicum nigrum had a greater capacity for growth and reproduction than V. rossicum, especially under drought. Drought reduced the probability of reproduction for V. rossicum. Vincetoxicum rossicum had a higher root-to-shoot ratio than V. nigrum under adequate soil moisture. This difference more than doubled under drought. Under interspecific competition, V. nigrum maxfectively limit Vincetoxicum growth and seed reproduction. Phenotypic plasticity and the positive competition intensity associated with drought in monocultures may contribute to drought resistance in these invasive species.Citizen science (CS) initiatives can transform how some ecological data are collected. Herbivory is a fundamental ecological interaction, but herbivory rates in many natural systems are unknown due in part to lack of personnel for monitoring efforts. This limits our ability to understand broad ecological patterns relevant to herbivory. Fortunately, accurate and reliable visual estimation techniques for assessing herbivory could be amenable to CS approaches. In 2008, I developed a CS training initiative (the "Million Leaf Project", MLP) to measure herbivory based on a 7-category visual assessment of leaf area removed (LAR). From 2010-2018, 394 citizen scientists assessed damage on 175,421 leaves to test the hypothesis that herbivory varies between understory and canopy leaves in a Peruvian tropical forest. In support of this hypothesis, the longitudinal CS data reveal that understory leaves consistently experience more herbivory than do canopy leaves on average (18.3% vs. 12.3%, P less then 0.001), a difference which was consistent regardless of CS observer age. Furthermore, data integrity was high, even though younger participants showed some leaf selection bias. The MLP is based on a simple technique, intended to broaden public participation in ecological science, and applicable to any ecological system in which herbivory or leaf damage occurs.Rosacea is a chronic, symptomatic and potentially disfiguring inflammatory skin condition with high prevalence, particularly among women.1 Quantitative research into the psychosocial factors associated with rosacea has consistently reported the presence of anxiety, depression, decreased quality of life and feelings of stigmatisation.2,3 Such factors may be challenging to identify in clinical practice, since the objective severity of a visible difference does not always correlate with the lived experience.4.Lightning is a common source of disturbance, but its ecological effects in tropical forests are largely undescribed. Here we quantify the contributions of lightning strikes to forest turnover and plant mortality in a lowland Panamanian forest using a real-time lightning monitoring system. We examined 2195 lightning-damaged trees distributed among 93 different strikes. None exhibited scars or fires. On average, each strike disturbed 451 m2 (95% CI 365-545 m2 ), created a canopy gap of 304 m2 (95% CI 198-454 m2 ), and caused 7.36 Mg of woody biomass turnover (CI 5.36-9.65 Mg). Cumulatively, we estimate that lightning strikes in this forest create canopy gaps equaling 0.39% of forest canopy area, representing 20.1% of annual gap area formation, and are responsible for 16.1% of total woody biomass turnover. Trees, lianas, herbaceous climbers, and epiphytes were killed by lightning at rates 8-29 times greater than their baseline mortality rates in undamaged control sites. The likelihood of lightning-caused death was higher for trees, lianas, and herbaceous climbers than for epiphytes, and high liana mortality suggests that lightning is an important driver of liana turnover. These results indicate that lightning influences gap dynamics, plant community composition, and carbon storage capacity in some tropical forests.

The aim of this work was to analyse the association of the retinal arteriolar calibre and the arteriole/venule index (AV index) with vascular ageing in a general population without previous cardiovascular disease.

Descriptive cross-sectional study. A total of 482 individuals without cardiovascular disease (mean age 55.6±14.2years) were selected by random sampling, stratified by age and sex. The retinal arteriolar calibre was measured using digital fundus images of the back of the eye captured with a validated, semiautomatized and computer-assisted software (Index calculator). Vascular ageing was defined using three criteria based on the values of (1) Carotid-femoral Pulse Wave Velocity (cfPWV), (2) Brachial-ankle Pulse Wave Velocity (baPWV) and (3) Carotid Intima-Media Thickness.

The AV index and arteriolar calibre show a negative correlation with age, arterial pressure, cardiovascular risk and parameters of vascular structure and function (p<0.001 in all cases). We found lower mean values of the AV in a general Spanish population without previous cardiovascular disease.

Merkel cell carcinoma (MCC) is an aggressive skin cancer, whose tumor cells often express CD56. While immune checkpoint inhibitors constitute a major advance for treating MCC patients with advanced disease, new therapeutic options are still urgently required.

The aim of this study was to produce and evaluate therapeutic performances of a new antibody-drug conjugate targeting CD56, named Adcitmer®, in preclinical models of MCC.

First, CD56 expression was evaluated in an MCC cohort (immunohistochemistry on tissue micro-array including 90 tumor samples) and MCC cell lines. Interaction of an unconjugated CD56-targeting antibody with CD56-positive MCC cell lines was investigated by immunohistochemistry and imaging flow cytometry. Adcitmer

product was generated by bioconjugation of CD56-targeting antibody to a cytotoxic drug (MMAE) using McSAF Inside

bioconjugation process. Chemical properties and homogeneity of Adcitmer

were characterized by hydrophobic interaction chromatography. Adcitmer

cytotoxicity was evaluated in vitro and in an MCC xenograft mice model.

Similar to previous reports, CD56 was expressed by 66% of MCC tumors in our cohort, confirming its relevance as therapeutic target. Specific binding and internalization of the unconjugated CD56-targeting antibody was validated in MCC cell lines. The high homogeneity of the newly generated Adcitmer

was confirmed by hydrophobic interaction chromatography. CD56-mediated cytotoxicity of Adcitmer

was demonstrated in vitro in MCC cell lines. Moreover, Adcitmer

significantly reduced tumor growth in a MCC mouse model.

Our study suggests Adcitmer® as a therapeutic option to be further assessed in MCC patients, as an alternative or combined with immune checkpoint inhibitors.

Our study suggests Adcitmer® as a therapeutic option to be further assessed in MCC patients, as an alternative or combined with immune checkpoint inhibitors.

Obesity was consistently associated with a poor prognosis in patients with COVID-19. Epigenetic mechanisms were proposed as the link between obesity and comorbidities risk.

To evaluate the methylation levels of angiotensin-converting enzyme 2 (ACE2) gene, the main entry receptor of SARS-CoV-2, in different depots of adipose tissue (AT) and leukocytes (PBMCs) in obesity and after weight loss therapy based on a very-low-calorie ketogenic diet (VLCKD), a balanced hypocaloric diet (HCD) or bariatric surgery (BS).

DNA methylation levels of ACE2 were extracted from our datasets generated by the hybridization of subcutaneous (SAT) (n=32) or visceral (VAT) (n=32) adipose tissue, and PBMCs (n=34) samples in Infinium HumanMethylation450 BeadChips. Data were compared based on the degree of obesity and after 4-6 months of weight loss either by following a nutritional or surgical treatment and correlated with ACE2 transcript levels.

As compared with normal weight, VAT from patients with obesity showed higher ACE2 methylation levels.

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