In September 2019, the research
icebreaker Polarstern started the largest multidisciplinary Arctic expedition to date,
the MOSAiC (Multidisciplinary drifting Observatory for the Study of Arctic
...Climate) drift experiment. Being moored to an ice floe for a whole year,
thus including the winter season, the declared goal of the expedition is to
better understand and quantify relevant processes within the
atmosphere–ice–ocean system that impact the sea ice mass and energy budget,
ultimately leading to much improved climate models. Satellite observations,
atmospheric reanalysis data, and readings from a nearby meteorological
station indicate that the interplay of high ice export in late winter and
exceptionally high air temperatures resulted in the longest ice-free summer
period since reliable instrumental records began. We show, using a
Lagrangian tracking tool and a thermodynamic sea ice model, that the MOSAiC
floe carrying the Central Observatory (CO) formed in a polynya event north
of the New Siberian Islands at the beginning of December 2018. The results
further indicate that sea ice in the vicinity of the CO (<40 km
distance) was younger and 36 % thinner than the surrounding ice with
potential consequences for ice dynamics and momentum and heat transfer
between ocean and atmosphere. Sea ice surveys carried out on various
reference floes in autumn 2019 verify this gradient in ice thickness, and
sediments discovered in ice cores (so-called dirty sea ice) around the CO
confirm contact with shallow waters in an early phase of growth, consistent
with the tracking analysis. Since less and less ice from the Siberian
shelves survives its first summer (Krumpen et al., 2019), the MOSAiC
experiment provides the unique opportunity to study the role of sea ice as a
transport medium for gases, macronutrients, iron, organic matter,
sediments and pollutants from shelf areas to the central Arctic Ocean and
beyond. Compared to data for the past 26 years, the sea ice encountered at
the end of September 2019 can already be classified as exceptionally thin,
and further predicted changes towards a seasonally ice-free ocean will
likely cut off the long-range transport of ice-rafted materials by the
Transpolar Drift in the future. A reduced long-range transport of sea ice
would have strong implications for the redistribution of biogeochemical
matter in the central Arctic Ocean, with consequences for the balance of
climate-relevant trace gases, primary production and biodiversity in the
Arctic Ocean.
Strategies to link impulsivity and self-injurious behaviors (SIBs) show highly variable results, and may differ depending on the impulsivity measure used. To better understand this lack of ...consistency, we investigated correlations between self-report and behavioral impulsivity, inhibitory control, SIBs, and rumination. We included participants aged 13-17 years with either current or remitted psychopathology who have (
= 31) and who do not have (
= 14) a history of SIBs. Participants completed self-report measures of impulsivity, the Rumination Responsiveness Scale (RRS), and two behavioral measures of impulsivity: the Balloon Analogue Risk Task (BART) and Parametric Go/No-Go (PGNG). Lifetime SIBs were positively associated with self-reported impulsivity, specifically positive and negative urgency. However, individuals with greater lifetime SIBs demonstrated greater risk aversion (lower impulsivity) as measured by the BART, whereas there was no relation between lifetime SIBs and PGNG performance. There was no relation between rumination and behavioral impulsivity, although greater rumination was associated with higher negative urgency. Future research examining the role of SIBs in the context of active versus remitted psychopathology is warranted. Because most adolescents were remitted from major depressive disorder at the time of study, follow-up studies can determine if lower risk-taking may aid individuals with more prior SIBs to achieve and maintain a remitted state.
Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related ...loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 × 10−6), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 10−8). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 × 10−11). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait.
Engendering cytotoxic T-lymphocyte (CTL) responses is likely to be an important goal of HIV vaccines. However, CTLs select for viral variants that escape immune detection. Maintenance of such escape ...variants in human populations could pose an obstacle to HIV vaccine development. We first observed that escape mutations in a heterogeneous simian immunodeficiency virus (SIV) isolate were lost upon passage to new animals. We therefore infected macaques with a cloned SIV bearing escape mutations in three immunodominant CTL epitopes, and followed viral evolution after infection. Here we show that each mutant epitope sequence continued to evolve in vivo, often re-establishing the original, CTL-susceptible sequence. We conclude that escape from CTL responses may exact a cost to viral fitness. In the absence of selective pressure upon transmission to new hosts, these original escape mutations can be lost. This suggests that some HIV CTL epitopes will be maintained in human populations.
An effective AIDS vaccine will need to protect against globally diverse isolates of HIV. To address this issue in macaques, we administered a live-attenuated simian immunodeficiency virus (SIV) ...vaccine and challenged with a highly pathogenic heterologous isolate. Vaccinees reduced viral replication by approximately 2 logs between weeks 2-32 (P < or = 0.049) postchallenge. Remarkably, vaccinees expressing MHC-I (MHC class I) alleles previously associated with viral control completely suppressed acute phase replication of the challenge virus, implicating CD8(+) T cells in this control. Furthermore, transient depletion of peripheral CD8(+) lymphocytes in four vaccinees during the chronic phase resulted in an increase in virus replication. In two of these animals, the recrudescent virus population contained only the vaccine strain and not the challenge virus. Alarmingly, however, we found evidence of recombinant viruses emerging in some of the vaccinated animals. This finding argues strongly against an attenuated virus vaccine as a solution to the AIDS epidemic. On a more positive note, our results suggest that MHC-I-restricted CD8(+) T cells contribute to the protection induced by the live-attenuated SIV vaccine and demonstrate that vaccine-induced CD8(+) T cell responses can control replication of heterologous challenge viruses.
An aim of molecular biomarkers is to stratify patients with cancer into disease subtypes predictive of outcome, improving diagnostic precision beyond clinical descriptors such as tumor stage
. ...Transcriptomic intratumor heterogeneity (RNA-ITH) has been shown to confound existing expression-based biomarkers across multiple cancer types
. Here, we analyze multi-region whole-exome and RNA sequencing data for 156 tumor regions from 48 patients enrolled in the TRACERx study to explore and control for RNA-ITH in non-small cell lung cancer. We find that chromosomal instability is a major driver of RNA-ITH, and existing prognostic gene expression signatures are vulnerable to tumor sampling bias. To address this, we identify genes expressed homogeneously within individual tumors that encode expression modules of cancer cell proliferation and are often driven by DNA copy-number gains selected early in tumor evolution. Clonal transcriptomic biomarkers overcome tumor sampling bias, associate with survival independent of clinicopathological risk factors, and may provide a general strategy to refine biomarker design across cancer types.
•Providing information on environmental consequences can reduce meat consumption.•Conveying health risks, norms, or providing smaller meat portions may be effective.•Few reviews include ...meta-analyses, so quantifying effect sizes is difficult.•Most reviews focus on meat, despite comparable concerns of other animal products.•Techniques to increase dairy intake could be used for plant-based alternatives.
Transitioning toward plant-based diets can alleviate health and sustainability challenges. However, research on interventions that influence animal-product consumption remains fragmented and inaccessible to researchers and practitioners. We conducted an overview of systematic reviews, also known as a meta-review. We searched five databases for reviews that examined interventions that influence (increase or decrease) the consumption of animal products. We quantitatively summarised results using individual studies' directions of effect because reviews rarely reported effect sizes of primary studies. Eighteen reviews met inclusion criteria, 12 of which examined interventions intended to decrease animal-product consumption and 6 of which examined interventions intended to increase animal-product consumption. In total, only two reviews conducted quantitative meta-analyses. Across all reviews, vote counting indicated that providing information on the environmental impact of meat consumption may reduce consumption, with 10 of 11 estimates suggesting reduced consumption (91%, 95% CI 62.3%, 98.4%; p = .012). Providing information on the health consequences, emphasising social norms, and reducing meat portion sizes also appeared promising, albeit with more limited evidence. Reviews examining interventions that decreased consumption predominately focused on meat (10/12 reviews). Future reviews should conduct quantitative syntheses where appropriate and examine interventions that influence the consumption of animal products other than meat.
Yellow fever virus (YFV) is a reemerging global health threat, driven by several factors, including increased spread of the mosquito vector and rapid urbanization. Although a prophylactic vaccine ...exists, vaccine hesitancy, supply deficits, and distribution difficulties leave specific populations at risk of severe YFV disease, as evidenced by recent outbreaks in South America. To establish a treatment for patients with severe YFV infection, we tested 37 YFV-specific monoclonal antibodies isolated from vaccinated humans and identified two capable of potently neutralizing multiple pathogenic primary YFV isolates. Using both hamster and nonhuman primate models of lethal YFV infection, we demonstrate that a single administration of either of these two potently neutralizing antibodies during acute infection fully controlled viremia and prevented severe disease and death in treated animals. Given the potential severity of YFV-induced disease, our results show that these antibodies could be effective in saving lives and fill a much-needed void in managing YFV cases during outbreaks.
PDF
