Combined Effects of Leaf Litter Inputs and a Flood on Nutrient Retention in a Mediterranean Mountain Stream During Fall

This study examined the effect of increasing in-channel leaf standing stocks on hydrologic transient storage and nutrient retention in a Mediterranean mountain stream. A flood at the end of the leaf fall period provided the opportunity to examine the effect of abrupt removal of much of the leaf material. Twenty-one chloride additions were performed from October to December 2004. In 13 of these, we also added ammonium and phosphate to estimate nutrient uptake lengths and uptake velocities to assess nutrient retention. The one-dimensional transport with inflow and storage (OTIS) model was used to estimate transient water storage parameters. Although discharge remained constant during leaf fall, water residence time increased because of in-channel litter accumulation, as did nutrient uptake velocity. Flooding reduced leaf benthic standing stocks by 65% and dramatically altered hydraulic and nutrient retention properties of the channel. After recession, the stream rapidly recovered in terms of nutrient retention, especially for phosphate. Abrupt changes in discharge under flood conditions largely determined the variability in stream nutrient retention. However, leaf litter inputs played an important role in nutrient dynamics during constant flow. Because both the flood regime and the timing of leaf fall are being regionally altered by climate change, our results have implications for stream nutrient dynamics under climate change scenarios

Overview of Checkpoint Inhibitors Mechanism of Action: Role of Immune-Related Adverse Events and Their Treatment on Progression of Underlying Cancer

Corticosteroids; Efficacy; Immune checkpoint inhibitorsCorticosteroides; Eficacia; Inhibidores del punto de control inmunitarioCorticoides; Eficàcia; Inhibidors del punt de control immunitariIn recent years, immunotherapy-based regimens have been included into the treatment's algorithm of several cancer types. Programmed death-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) interact with their ligands found on the surface of antigen presenting cells (APC) or tumor cells (PD-L1/2 and CD80/86). Through these interactions, stimulatory or inhibitory signals are established. Immune checkpoint inhibitors (ICIs), block these interactions, and when administered not only as monotherapy but also as part of combination regimens, have shown to improve survival results in multiple advanced cancers leading to an increasing number of patients treated with ICI and, as a consequence, a rise in the number of patients developing immune-related adverse events (irAEs). Presence of irAEs has been associated with greater benefit from treatment, especially when blocking PD-L1. Recent data suggests that treatment benefit persists after discontinuation of ICIs due to a treatment related adverse event, regardless of the grade. Patients experiencing grade 3-4 irAEs are at risk of toxicity recurrence after reintroducing immunotherapy and therefore, the decision to resume the treatment is challenging. In these cases, a multidisciplinary approach is always needed and several factors should be considered. Management of severe toxicities may require systemic corticosteroids which can impact on T-cell function. Due to their immunosuppressive properties, it is necessary to deeper determine how corticosteroids influence responses. In terms of overall survival (OS), the use of steroids as therapy for irAEs seems not to reduce OS and several studies have reported durable responses in patients experiencing autoimmune toxicities treated with corticosteroids

Multi-ancestry GWAS reveals excitotoxicity associated with outcome after ischaemic stroke

During the first hours after stroke onset, neurological deficits can be highly unstable: some patients rapidly improve, while others deteriorate. This early neurological instability has a major impact on long-term outcome. Here, we aimed to determine the genetic architecture of early neurological instability measured by the difference between the National Institutes of Health Stroke Scale (NIHSS) within 6 h of stroke onset and NIHSS at 24 h. A total of 5876 individuals from seven countries (Spain, Finland, Poland, USA, Costa Rica, Mexico and Korea) were studied using a multi-ancestry meta-analyses. We found that 8.7% of NIHSS at 24 h of variance was explained by common genetic variations, and also that early neurological instability has a different genetic architecture from that of stroke risk. Eight loci (1p21.1, 1q42.2, 2p25.1, 2q31.2, 2q33.3, 5q33.2, 7p21.2 and 13q31.1) were genome-wide significant and explained 1.8% of the variability suggesting that additional variants influence early change in neurological deficits. We used functional genomics and bioinformatic annotation to identify the genes driving the association from each locus. Expression quantitative trait loci mapping and summary data-based Mendelian randomization indicate that ADAM23 (log Bayes factor = 5.41) was driving the association for 2q33.3. Gene-based analyses suggested that GRIA1 (log Bayes factor = 5.19), which is predominantly expressed in the brain, is the gene driving the association for the 5q33.2 locus. These analyses also nominated GNPAT (log Bayes factor = 7.64) ABCB5 (log Bayes factor = 5.97) for the 1p21.1 and 7p21.1 loci. Human brain single-nuclei RNA-sequencing indicates that the gene expression of ADAM23 and GRIA1 is enriched in neurons. ADAM23, a presynaptic protein and GRIA1, a protein subunit of the AMPA receptor, are part of a synaptic protein complex that modulates neuronal excitability. These data provide the first genetic evidence in humans that excitotoxicity may contribute to early neurological instability after acute ischaemic stroke. Ibanez et al. perform a multi-ancestry meta-analysis to investigate the genetic architecture of early stroke outcomes. Two of the eight genome-wide significant loci identified-ADAM23 and GRIA1-are involved in synaptic excitability, suggesting that excitotoxicity contributes to neurological instability after ischaemic stroke.Peer reviewe

Particulate matter exposure during pregnancy is associated with birth weight, but not gestational age, 1962-1992: a cohort study

<p>Abstract</p> <p>Background</p> <p>Exposure to air pollutants is suggested to adversely affect fetal growth, but the evidence remains inconsistent in relation to specific outcomes and exposure windows.</p> <p>Methods</p> <p>Using birth records from the two major maternity hospitals in Newcastle upon Tyne in northern England between 1961 and 1992, we constructed a database of all births to mothers resident within the city. Weekly black smoke exposure levels from routine data recorded at 20 air pollution monitoring stations were obtained and individual exposures were estimated via a two-stage modeling strategy, incorporating temporally and spatially varying covariates. Regression analyses, including 88,679 births, assessed potential associations between exposure to black smoke and birth weight, gestational age and birth weight standardized for gestational age and sex.</p> <p>Results</p> <p>Significant associations were seen between black smoke and both standardized and unstandardized birth weight, but not for gestational age when adjusted for potential confounders. Not all associations were linear. For an increase in whole pregnancy black smoke exposure, from the 1^st(7.4 μg/m³) to the 25^th(17.2 μg/m³), 50^th(33.8 μg/m³), 75^th(108.3 μg/m³), and 90^th(180.8 μg/m³) percentiles, the adjusted estimated decreases in birth weight were 33 g (SE 1.05), 62 g (1.63), 98 g (2.26) and 109 g (2.44) respectively. A significant interaction was observed between socio-economic deprivation and black smoke on both standardized and unstandardized birth weight with increasing effects of black smoke in reducing birth weight seen with increasing socio-economic disadvantage.</p> <p>Conclusions</p> <p>The findings of this study progress the hypothesis that the association between black smoke and birth weight may be mediated through intrauterine growth restriction. The associations between black smoke and birth weight were of the same order of magnitude as those reported for passive smoking. These findings add to the growing evidence of the harmful effects of air pollution on birth outcomes.</p

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Evaluation of Pre-treatments of Brewery’s Spent Grain for Growing Bacteria in the Production of Polyhydroxyalkanoates

A suitable solution to solve the problems related to the conventional plastics is their replacement by biodegradable materials with similar properties such as polyhydroxyalkanoates (PHAs). PHAs can be produced by microorganisms using abundant low-cost substrates such as brewery’s spent grain (BSG). In this work, different pre-treatments were tested on BSG to improve the growth and production of biomass using three different strains highly recognized for their ability to produce PHA. A solid-state fermentation (SSF) was carried out to evaluate PHA production. An evaluation of biomass growth kinetics of the three selected bacteria was made after different hydrolytic pre-treatments of BSG. Results showed that bacteria did not grow in control BSG and the pre-treatments were necessary to release the principal substrate metabolised by bacteria. The best result was obtained with alkali pre-treatment although microwave pre-treatment showed good results too. The strains P. putida and C. necator showed productions of 1.95 and 1.45 mg biomass/g BSG and viable cell counts of 1.5 E+16 and 1.3 E+08 CFU/g BSG after 72 hours of SSF, respectively. On the other hand, Bacillus cereus was not able to grow in the pre-treated substrates. BSG is a promising substrate for bacterial growth and PHA production for its nutrient content.This study was supported by the VALORA project (CTM2016-81038-R) from the Spanish Ministry of Economy and Competitiveness. D. A. Mendez acknowledges a fellowship gave by “Proyecto de formación de talento humano de alto nivel - Tolima“ from Universidad del Tolim

El Neolitico antiguo en la zona oriental de la Peninsula Iberica

De nouvelles fouilles sur la façade orientale de la Péninsule Ibérique permettent d’évaluer l’importance du substrat épipaléolithique et des influences méditerranéennes qui précèdent l’épanouissement du Néolithique. L’on définit les caractéristiques principales du Néolithique, de sa culture matérielle et de son activité économique, ainsi que la chronologie et les phases de son évolution. Les animaux domestiques et leur signification, la faune malacologique dans son double aspect d’élément ornemental et de complément de l’alimentation, ainsi que l’évolution de la technologie de la céramique, en étroite relation avec les changements qu’enregistrent ces récipients au cours du Néolithique, sont l’objet d’une attention spéciale.New excavations on the east coast of the Iberian peninsula will make it possible to assess the importance of the epipaleolithic substratum and of Neolithic age. As soon as its evolution can be divided chronologically into stages, the main characteristics of the material culture, together with its ecomic activity, will hopefully be determined. We are particularly interested in domestic animals and their special significance, shellfish serving two purposes : decoration an diet, and the development of ceramic technology with particular reference to changes in the use of receptacles.Nuevas excavaciones en la fachada oriental de la Peninsula Ibérica permiten valorar la importancia del substrato epipaleolítico y de las influencias mediterráneas que subyacen al florecimiento del Neolítico. Se definen las características principales de su cultura material y de su actividad económica, así como la cronología y las fases en que puede dividirse su evolución. Los animales domésticos y su particular significado, la malacofauna en su doble vertiente de elemento ornamental y de complemento de la dieta, y la evolución de la tecnología cerámica en estrecha relación con los cambios que estos recipientes experimentan durante el Neolítico, son objeto de especial atención

Interactions between the atmosphere and the land surface at night under semi-arid conditions

Most studies on water flow dynamics within the soil-plant-atmosphere system focus on the daytime, but not on the processes at night. Evapotranspiration (ET), which is the second largest water flow in the global terrestrial water cycle after precipitation, occurs mainly during the day. There is, however, evidence that a considerable amount of water loss through ET also occurs at night. Nocturnal water losses are counteracted by the formation of non-rainfall water inputs (NRW) from dew formation, fog, and water vapour adsorption. To better capture the interplay of different nocturnal water fluxes, observations and models need to account not only for evaporation and transpiration processes, but also on formation of NRW inputs. This is particularly important for arid and semi-arid areas, where every drop of water counts, as the ecosystems there can only draw on limited water resources. We used a high precision weighable lysimeter, a leaf wetness sensor and meteorological observation to quantify nocturnal water fluxes and identify which mechanisms govern nocturnal water fluxes under water limited conditions during the intensive measurement campaign of LIAISE in July 2021