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Abstract Background Aldehyde dehydrogenase 2 (ALDH2) is critical for alcohol metabolism by converting acetaldehyde to acetic acid. In East Asian descendants, an inactive genetic variant in ALDH2, rs671, triggers an alcohol flushing response due to acetaldehyde accumulation. As alcohol flushing is not exclusive to those of East Asian descent, we questioned whether additional ALDH2 genetic variants can drive facial flushing and inefficient acetaldehyde metabolism using human testing and biochemical assays. Methods After IRB approval, human subjects were given an alcohol challenge (0.25 g/kg) while quantifying acetaldehyde levels and the physiological response (heart rate and skin temperature) to alcohol. Further, by employing biochemical techniques including human purified ALDH2 proteins and transiently transfected NIH 3T3 cells, we characterized two newly identified ALDH2 variants for ALDH2 enzymatic activity, ALDH2 dimer/tetramer formation, and reactive oxygen species production after alcohol treatment. Results Humans heterozygous for rs747096195 (R101G) or rs190764869 (R114W) had facial flushing and a 2-fold increase in acetaldehyde levels, while rs671 (E504K) had facial flushing and a 6-fold increase in acetaldehyde levels relative to wild type ALDH2 carriers. In vitro studies with recombinant R101G and R114W ALDH2 enzyme showed a reduced efficiency in acetaldehyde metabolism that is unique when compared to E504K or wild-type ALDH2. The effect is caused by a lack of functional dimer/tetramer formation for R101G and decreased Vmax for both R101G and R114W. Transiently transfected NIH-3T3 cells with R101G and R114W also had a reduced enzymatic activity by ~ 50% relative to transfected wild-type ALDH2 and when subjected to alcohol, the R101G and R114W variants had a 2-3-fold increase in reactive oxygen species formation with respect to wild type ALDH2. Conclusions We identified two additional ALDH2 variants in humans causing facial flushing and acetaldehyde accumulation after alcohol consumption. As alcohol use is associated with a several-fold higher risk for esophageal cancer for the E504K variant, the methodology developed here to characterize ALDH2 genetic variant response to alcohol can lead the way precision medicine strategies to further understand the interplay of alcohol consumption, ALDH2 genetics, and cancer.

Understanding plant physiological response to a rising atmospheric CO2 concentration (ca) is key in predicting Earth system plant–climate feedbacks; however, the effects of long-term rising ca on plant gas-exchange characteristics in the tropics are largely unknown. Studying this long-term trend using herbarium records is challenging due to specimen trait variation. We assessed the impact of a ca rise of ~95 ppm (1927–2015) on the intrinsic water-use efficiency (iWUE) and maximum stomatal conductance (gsmax) of five tropical tree species in Fiji using the isotopic composition and stomatal traits of herbarium leaves. Empirical results were compared with simulated values using models that uniquely incorporated the variation in the empirical gsmax responses and species-specific parameterisation. The magnitude of the empirical iWUE and gsmax response was species-specific, ranging from strong to negligible. Stomatal density was more influential than the pore size in determining the gsmax response to ca. While our simulation results indicated that photosynthesis is the main factor contributing to the iWUE gain, stomata were driving the iWUE trend across the tree species. Generally, a stronger increase in the iWUE was accompanied by a stronger decline in stomatal response. This study demonstrates that the incorporation of variation in the gsmax in simulations is necessary for assessing an individual species’ iWUE response to changing ca.

No abstract available.

Inferior vena cava (IVC) anomalies will remain silent until collateralized venous drainage has been lost. The initial signs can be subtle, including back pain, and are often missed initially until progressive changes toward motor weakness, phlegmasia cerulea dolens, and/or renal impairment have occurred. We have presented a case of acute occlusion of an atretic IVC and infrarenal collateral drainage in an adolescent patient, who had been treated with successful thrombolysis, thrombectomy, and endovascular revascularization for IVC stenting and reconstruction.

We have presented the successful endovascular management of an injury to the proximal left common carotid artery following attempted cannulation of the right internal jugular vein in a critically ill patient with multisystem organ failure secondary to infection with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2).

Summary: Inguinal white adipose tissue (iWAT) is essential for the beneficial effects of exercise training on metabolic health. The underlying mechanisms for these effects are not fully understood, and here, we test the hypothesis that exercise training results in a more favorable iWAT structural phenotype. Using biochemical, imaging, and multi-omics analyses, we find that 11 days of wheel running in male mice causes profound iWAT remodeling including decreased extracellular matrix (ECM) deposition and increased vascularization and innervation. We identify adipose stem cells as one of the main contributors to training-induced ECM remodeling, show that the PRDM16 transcriptional complex is necessary for iWAT remodeling and beiging, and discover neuronal growth regulator 1 (NEGR1) as a link between PRDM16 and neuritogenesis. Moreover, we find that training causes a shift from hypertrophic to insulin-sensitive adipocyte subpopulations. Exercise training leads to remarkable adaptations to iWAT structure and cell-type composition that can confer beneficial changes in tissue metabolism.

The evolution of woody stems approximately 400 mya (middle Paleozoic) facilitated the expansion of plants and has likely affected carbon and water budgets across much of the terrestrial surface since that time. Stems are a carbon cost/sink and limit water transport from soil to leaves as it must pass through specialized xylem tissue. While leaf fossils have provided a wealth of quantitative data, including estimates of plant water fluxes utilizing biophysically based models, fossil-informed models integrating stem and leaf physiology are lacking. Integrated stem-leaf physiology may distinguish successors to ecological catastrophes like the end of the Late Paleozoic Ice Age (LPIA). The documented collapse of LPIA tropical forests provides an opportunity to assess the importance of woody stems as a key to understanding differences in survivorship among common plant taxa from the Carboniferous to the Permian. Here, we present an analysis of the limits to leaf water supply and plant function for Paleozoic forest plant types due to (1) cavitation-induced embolism and xylem blockage and (2) insufficient sapwood water transport capacity.—collectively defined here as sapwood dysfunction. We first present a modified ecosystem process model (Paleo-BGC+) that includes sapwood dysfunction. Paleo-BGC + is parameterized using measurements obtainable from fossil xylem and therefore applicable to both modern and ancient ecosystems. We then assess the effect of sapwood dysfunction on ecosystem processes based on previously published fossil leaf measurements and a new fossil xylem dataset for plant types present in the Late Paleozoic. Using daily meteorology from a GCM of the late Carboniferous (GENESIS v3) under a Glacial (low-CO2) and an Inter-glacial (high-CO2) scenario, we found that simulated sapwood dysfunction slowed plant water use and reduced carbon storage. This inhibition occurred particularly in plants with high maximum stomatal conductance and high stem vulnerability to embolism. Coincidentally, plants with these traits were predominantly reduced or missing from the fossil record from the Carboniferous to the Permian. Integrating stem and leaf physiology may improve the fidelity of model representations of soil-to-atmosphere water transport through plants, simulations of long-term climate phenomena like the LPIA, and ecosystem projections under future climate change.

In this work, we developed a data-driven framework to predict near-surface (0–5 cm) soil moisture (SM) by mapping inputs from the Soil & Water Assessment Tool to SM time series from NASA’s Soil Moisture Active Passive (SMAP) satellite for the period 1 January 2016–31 December 2018. We developed a hybrid artificial neural network (ANN) combining long short-term memory and multilayer perceptron networks that were used to simultaneously incorporate dynamic weather and static spatial data into the training algorithm, respectively. We evaluated the generalizability of the hybrid ANN using training datasets comprising several watersheds with different environmental conditions, examined the effects of standard and physics-guided loss functions, and experimented with feature augmentation. Our model could estimate SM on par with the accuracy of SMAP. We demonstrated that the most critical learning of the physical processes governing SM variability was learned from meteorological time series, and that additional physical context supported model performance when test data were not fully encapsulated by the variability of the training data. Additionally, we found that when forecasting SM based on trends learned during the earlier training period, the models appreciated seasonal trends.

Abstract Huntington’s disease (HD) is characterized by protein inclusions and loss of striatal neurons which result from expanded CAG repeats in the poly-glutamine (polyQ) region of the huntingtin (HTT) gene. Both polyQ expansion and loss of HTT have been shown to cause axonal transport defects. While studies show that HTT is important for vesicular transport within axons, the cargo that HTT transports to/from synapses remain elusive. Here, we show that HTT is present with a class of Rab4-containing vesicles within axons in vivo. Reduction of HTT perturbs the bi-directional motility of Rab4, causing axonal and synaptic accumulations. In-vivo dual-color imaging reveal that HTT and Rab4 move together on a unique putative vesicle that may also contain synaptotagmin, synaptobrevin, and Rab11. The moving HTT-Rab4 vesicle uses kinesin-1 and dynein motors for its bi-directional movement within axons, as well as the accessory protein HIP1 (HTT-interacting protein 1). Pathogenic HTT disrupts the motility of HTT-Rab4 and results in larval locomotion defects, aberrant synaptic morphology, and decreased lifespan, which are rescued by excess Rab4. Consistent with these observations, Rab4 motility is perturbed in iNeurons derived from human Huntington’s Disease (HD) patients, likely due to disrupted associations between the polyQ-HTT-Rab4 vesicle complex, accessory proteins, and molecular motors. Together, our observations suggest the existence of a putative moving HTT-Rab4 vesicle, and that the axonal motility of this vesicle is disrupted in HD causing synaptic and behavioral dysfunction. These data highlight Rab4 as a potential novel therapeutic target that could be explored for early intervention prior to neuronal loss and behavioral defects observed in HD.

Abstract Objective: To evaluate infectious pathogen transmission data visualizations in outbreak publications. Design: Scoping review. Methods: Medline was searched for outbreak investigations of infectious diseases within healthcare facilities that included ≥1 data visualization of transmission using data observable by an infection preventionist showing temporal and/or spatial relationships. Abstracted data included the nature of the cluster(s) (pathogen, scope of transmission, and individuals involved) and data visualization characteristics including visualization type, transmission elements, and software. Results: From 1,957 articles retrieved, we analyzed 30 articles including 37 data visualizations. The median cluster size was 20.5 individuals (range, 7–1,963) and lasted a median of 214 days (range, 12–5,204). Among the data visualization types, 10 (27%) were floor-plan transmission maps, 6 (16%) were timelines, 11 (30%) were transmission networks, 3 (8%) were Gantt charts, 4 (11%) were cluster map, and 4 (11%) were other types. In addition, 26 data visualizations (70%) contained spatial elements, 26 (70%) included person type, and 19 (51%) contained time elements. None of the data visualizations contained contagious periods and only 2 (5%) contained symptom-onset date. Conclusions: The data visualizations of healthcare-associated infectious disease outbreaks in the systematic review were diverse in type and visualization elements, though no data visualization contained all elements important to deriving hypotheses about transmission pathways. These findings aid in understanding the visualizing transmission pathways by describing essential elements of the data visualization and will inform the creation of a standardized mapping tool to aid in earlier initiation of interventions to prevent transmission.

Tectonic faults weaken during slip in order to accelerate and produce earthquakes. Here the authors show a mechanism for weakening faults through the transformation of quartz to amorphous nanoparticulate wear powders that lubricate friction experiments, and transform back to quartz under geologic conditions.

Microorganisms that thrive in hypersaline environments on the surface of our planet are exposed to the harmful effects of ultraviolet radiation. Therefore, for their protection, they have sunscreen pigments and highly efficient DNA repair and protection systems. The present study aimed to identify new genes involved in UV radiation resistance from these microorganisms, many of which cannot be cultured in the laboratory. Thus, a functional metagenomic approach was used and for this, small-insert libraries were constructed with DNA isolated from microorganisms of high-altitude Andean hypersaline lakes in Argentina (Diamante and Ojo Seco lakes, 4,589 and 3,200 m, respectively) and from the Es Trenc solar saltern in Spain. The libraries were hosted in a UV radiation-sensitive strain of Escherichia coli (recA mutant) and they were exposed to UVB. The resistant colonies were analyzed and as a result, four clones were identified with environmental DNA fragments containing five genes that conferred resistance to UV radiation in E. coli. One gene encoded a RecA-like protein, complementing the mutation in recA that makes the E. coli host strain more sensitive to UV radiation. Two other genes from the same DNA fragment encoded a TATA-box binding protein and an unknown protein, both responsible for UV resistance. Interestingly, two other genes from different and remote environments, the Ojo Seco Andean lake and the Es Trenc saltern, encoded two hypothetical proteins that can be considered homologous based on their significant amino acid similarity (49%). All of these genes also conferred resistance to 4-nitroquinoline 1-oxide (4-NQO), a compound that mimics the effect of UV radiation on DNA, and also to perchlorate, a powerful oxidant that can induce DNA damage. Furthermore, the hypothetical protein from the Es Trenc salterns was localized as discrete foci possibly associated with damaged sites in the DNA in cells treated with 4-NQO, so it could be involved in the repair of damaged DNA. In summary, novel genes involved in resistance to UV radiation, 4-NQO and perchlorate have been identified in this work and two of them encoding hypothetical proteins that could be involved in DNA damage repair activities not previously described.

Scanning electron microscopy (SEM) is widely used to investigate the surface morphology, and physiological state of plant leaves. Conventionally used methods for sample preparation are invasive, irreversible, require skill and expensive equipment, and are time and labor consuming. This study demonstrates a method to obtain in vivo surface information of plant leaves by imaging replicas with SEM that is rapid and non-invasive. Dental putty was applied to the leaves for 5 minutes and then removed. Replicas were then imaged with SEM and compared to fresh leaves, and leaves that were processed conventionally by chemical fixation, dehydration and critical point drying. The surface structure of leaves was well preserved on the replicas. The outline of epidermal as well as guard cells could be clearly distinguished enabling determination of stomatal density. Comparison of the dimensions of guard cells revealed that replicas did not differ from fresh leaves, while conventional sample preparation induced strong shrinkage (-40% in length and -38% in width) of the cells when compared to guard cells on fresh leaves. Tilting the replicas enabled clear measurement of stomatal aperture dimensions. Summing up, the major advantages of this method are that it is inexpensive, non-toxic, simple to apply, can be performed in the field, and that results on stomatal density and in vivo stomatal dimensions in 3D can be obtained in a few minutes.

The rise in obesity over the last several decades has reached pandemic proportions. Brown adipose tissue (BAT) is a thermogenic organ that is involved in energy expenditure and represents an attractive target to combat both obesity and type 2 diabetes. Cold exposure and exercise training are two stimuli that have been investigated with respect to BAT activation, metabolism, and the contribution of BAT to metabolic health. These two stimuli are of great interest because they have both disparate and converging effects on BAT activation and metabolism. Cold exposure is an effective mechanism to stimulate BAT activity and increase glucose and lipid uptake through mitochondrial uncoupling, resulting in metabolic benefits including elevated energy expenditure and increased insulin sensitivity. Exercise is a therapeutic tool that has marked benefits on systemic metabolism and affects several tissues, including BAT. Compared to cold exposure, studies focused on BAT metabolism and exercise display conflicting results; the majority of studies in rodents and humans demonstrate a reduction in BAT activity and reduced glucose and lipid uptake and storage. In addition to investigations of energy uptake and utilization, recent studies have focused on the effects of cold exposure and exercise on the structural lipids in BAT and secreted factors released from BAT, termed batokines. Cold exposure and exercise induce opposite responses in terms of structural lipids, but an important overlap exists between the effects of cold and exercise on batokines. In this review, we will discuss the similarities and differences of cold exposure and exercise in relation to their effects on BAT activity and metabolism and its relevance for the prevention of obesity and the development of type 2 diabetes.

Fibre channel storage area networks (SAN) are widely implemented in production data center environments. Recently the storage industry has moved towards deployment of distributed SANs (DSAN), geographically dispersed across large physical distances. In a DSAN, specialized gateway devices interconnect the individual Fibre Channel (FC) fabrics over IP networks using TCP/IP based protocols (iFCP or FCIP) or over metro to long distance optical networks such as Dense Wavelength Division Multiplexing (DWDM) based networks that utilize native FC ports supporting large numbers of link credits. When using TCP/IP based storage networking protocols to interconnect local FC fabrics in a DSAN, the sustained throughput achievable depends upon the link characteristics and TCP/IP stack implementation. Sustaining maximum possible storage traffic throughput across the wide area network enables practical DSAN deployments by maintaining the required site to site service level agreements.This study explores the effects of several TCP/IP modifications on sustained traffic throughput for a DSAN interconnected via iFCP gateways across an impaired network. The TCP/IP stack modifications, known as storage friendly, include changes to the window scaling, congestion avoidance, and fast recovery algorithms. The theoretical background and experimental results are presented to explain and illustrate these modifications.

Seed dispersal allows successive generations of plants to be mobile in space and time. Heeria argentea’s unusual fruit and its ubiquity in extremely rocky habitats, suggests that this tree requires a specialist disperser. We therefore investigated the dispersal ecology of H. argentea and Hartogiella schinoides. We found M. namaquensis rapidly removed H. argentea and H. schinoides fruits, moving them short distances within and between rock outcrops, and consumed only the pericarps. Birds were observed consuming H. schinoides, but not H. argentea fruits, suggesting M. namaquensis is its sole, specialist disperser. Most H. argentea seeds (65%) with removed pericarps germinated successfully, while intact fruits did not. We show rock outcrops represent fire refugia, allowing H. argentea trees to grow to large sizes, with small stems and a co-occurring, wind-dispersed tree, Widdringtonia nodiflora found away from these sites. This rodent–tree mutualism is perhaps the clearest global example of directed dispersal and shows that these endemic trees are highly adapted for survival in the southwestern Cape habitat and are not tropical relicts. Significance: • The fruits of rock-restricted Cape trees are directly dispersed by rock rats to rock outcrops. This is the first description of rodent dispersal of fleshy fruits in South Africa. • This species-specific interaction allows for rapid germination of seeds and protection from frequent fires for adults. This rodent–tree mutualism is perhaps the clearest global example of directed seed dispersal. Supplementary Video 1: https://youtu.be/qOgylIJSKpI Supplementary Video 2: https://youtu.be/4jWIUrtzpUk Supplementary Video 3: https://youtu.be/FtBmh-3oYi4

Scarabaeus spretus zur Strassen was observed to roll and bury Ceratocaryum argenteum (Restionaceae) seeds in the sandplain fynbos of the Potberg area of the De Hoop Nature Reserve, South Africa. This species is the second dung beetle species found to be deceived by the faecal mimicry of C. argenteum seeds – the first species being Epirinus flagellatus. An isotopic analysis suggests that both these dung beetle species most likely feed on eland (Taurotragus oryx), not bontebok (Damaliscus pygargus pygargus), dung. Thus the model in this mimicry is eland dung; this interaction suggests large herbivores are an integral part of this fynbos. Supplementary Video: A Scarabaeus spretus dung beetle burying seeds of Ceratocaryum argenteum: https://youtu.be/C_VFlAcsx10

Unlike virtually any other cells in the human body, neurons are tasked with the unique problem of transporting important factors from sites of synthesis at the cell bodies, across enormous distances, along narrow-caliber projections, to distally located nerve terminals in order to maintain cell viability. As a result, axonal transport is a highly regulated process whereby necessary cargoes of all types are packaged and shipped from one end of the neuron to the other. Interruptions in this finely tuned transport have been linked to many neurodegenerative disorders including Alzheimer’s (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) suggesting that this pathway is likely perturbed early in disease progression. Therefore, developing therapeutics targeted at modifying transport defects could potentially avert disease progression. In this review, we examine a variety of potential compounds identified from marine aquatic species that affect the axonal transport pathway. These compounds have been shown to function in microtubule (MT) assembly and maintenance, motor protein control, and in the regulation of protein degradation pathways, such as the autophagy-lysosome processes, which are defective in many degenerative diseases. Therefore, marine compounds have great potential in developing effective treatment strategies aimed at early defects which, over time, will restore transport and prevent cell death.