Lake Okeechobee, FL, USA, has been subjected to intensifying cyanobacterial blooms that can spread to the adjacent St. Lucie River and Estuary via natural and anthropogenically-induced flooding ...events. In July 2016, a large, toxic cyanobacterial bloom occurred in Lake Okeechobee and throughout the St. Lucie River and Estuary, leading Florida to declare a state of emergency. This study reports on measurements and nutrient amendment experiments performed in this freshwater-estuarine ecosystem (salinity 0-25 PSU) during and after the bloom. In July, all sites along the bloom exhibited dissolved inorganic nitrogen-to-phosphorus ratios < 6, while Microcystis dominated (> 95%) phytoplankton inventories from the lake to the central part of the estuary. Chlorophyll a and microcystin concentrations peaked (100 and 34 μg L-1, respectively) within Lake Okeechobee and decreased eastwards. Metagenomic analyses indicated that genes associated with the production of microcystin (mcyE) and the algal neurotoxin saxitoxin (sxtA) originated from Microcystis and multiple diazotrophic genera, respectively. There were highly significant correlations between levels of total nitrogen, microcystin, and microcystin synthesis gene abundance across all surveyed sites (p < 0.001), suggesting high levels of nitrogen supported the production of microcystin during this event. Consistent with this, experiments performed with low salinity water from the St. Lucie River during the event indicated that algal biomass was nitrogen-limited. In the fall, densities of Microcystis and concentrations of microcystin were significantly lower, green algae co-dominated with cyanobacteria, and multiple algal groups displayed nitrogen-limitation. These results indicate that monitoring and regulatory strategies in Lake Okeechobee and the St. Lucie River and Estuary should consider managing loads of nitrogen to control future algal and microcystin-producing cyanobacterial blooms.
Copper metal is in theory a viable oxidative electrocatalyst based on surface oxidation to CuIII and/or CuIV, but its use in water oxidation has been impeded by anodic corrosion. The in situ ...formation of an efficient interfacial oxygen‐evolving Cu catalyst from CuII in concentrated carbonate solutions is presented. The catalyst necessitates use of dissolved CuII and accesses the higher oxidation states prior to decompostion to form an active surface film, which is limited by solution conditions. This observation and restriction led to the exploration of ways to use surface‐protected Cu metal as a robust electrocatalyst for water oxidation. Formation of a compact film of CuO on Cu surface prevents anodic corrosion and results in sustained catalytic water oxidation. The Cu/CuO surface stabilization was also applied to Cu nanowire films, which are transparent and flexible electrocatalysts for water oxidation and are an attractive alternative to ITO‐supported catalysts for photoelectrochemical applications.
It's elementary! Copper can serve as a robust and transparent electrocatalyst for water oxidation in concentrated carbonate solutions. Formation of a compact layer of CuO intermediate from the underlying copper is found to prevent severe anodic corrosion, thus allowing sustained catalytic water oxidation.
Neuromusculoskeletal disorders affecting walking ability are often difficult to manage, in part due to limited understanding of how a patient's lower extremity muscle excitations contribute to the ...patient's lower extremity joint moments. To assist in the study of these disorders, researchers have developed electromyography (EMG) driven neuromusculoskeletal models utilizing scaled generic musculoskeletal geometry. While these models can predict individual muscle contributions to lower extremity joint moments during walking, the accuracy of the predictions can be hindered by errors in the scaled geometry. This study presents a novel EMG-driven modeling method that automatically adjusts surrogate representations of the patient's musculoskeletal geometry to improve prediction of lower extremity joint moments during walking. In addition to commonly adjusted neuromusculoskeletal model parameters, the proposed method adjusts model parameters defining muscle-tendon lengths, velocities, and moment arms. We evaluated our EMG-driven modeling method using data collected from a high-functioning hemiparetic subject walking on an instrumented treadmill at speeds ranging from 0.4 to 0.8 m/s. EMG-driven model parameter values were calibrated to match inverse dynamic moments for five degrees of freedom in each leg while keeping musculoskeletal geometry close to that of an initial scaled musculoskeletal model. We found that our EMG-driven modeling method incorporating automated adjustment of musculoskeletal geometry predicted net joint moments during walking more accurately than did the same method without geometric adjustments. Geometric adjustments improved moment prediction errors by 25% on average and up to 52%, with the largest improvements occurring at the hip. Predicted adjustments to musculoskeletal geometry were comparable to errors reported in the literature between scaled generic geometric models and measurements made from imaging data. Our results demonstrate that with appropriate experimental data, joint moment predictions for walking generated by an EMG-driven model can be improved significantly when automated adjustment of musculoskeletal geometry is included in the model calibration process.
An average shotgun proteomics experiment detects approximately 10,000 human proteins from a single sample. However, individual proteins are typically identified by peptide sequences representing a ...small fraction of their total amino acids. Hence, an average shotgun experiment fails to distinguish different protein variants and isoforms. Deeper proteome sequencing is therefore required for the global discovery of protein isoforms. Using six different human cell lines, six proteases, deep fractionation and three tandem mass spectrometry fragmentation methods, we identify a million unique peptides from 17,717 protein groups, with a median sequence coverage of approximately 80%. Direct comparison with RNA expression data provides evidence for the translation of most nonsynonymous variants. We have also hypothesized that undetected variants likely arise from mutation-induced protein instability. We further observe comparable detection rates for exon-exon junction peptides representing constitutive and alternative splicing events. Our dataset represents a resource for proteoform discovery and provides direct evidence that most frame-preserving alternatively spliced isoforms are translated.
Over 40 000 patients with COVID-19 have been hospitalised in New York City (NY, USA) as of April 28, 2020. Data on the epidemiology, clinical course, and outcomes of critically ill patients with ...COVID-19 in this setting are needed.
This prospective observational cohort study took place at two NewYork-Presbyterian hospitals affiliated with Columbia University Irving Medical Center in northern Manhattan. We prospectively identified adult patients (aged ≥18 years) admitted to both hospitals from March 2 to April 1, 2020, who were diagnosed with laboratory-confirmed COVID-19 and were critically ill with acute hypoxaemic respiratory failure, and collected clinical, biomarker, and treatment data. The primary outcome was the rate of in-hospital death. Secondary outcomes included frequency and duration of invasive mechanical ventilation, frequency of vasopressor use and renal replacement therapy, and time to in-hospital clinical deterioration following admission. The relation between clinical risk factors, biomarkers, and in-hospital mortality was modelled using Cox proportional hazards regression. Follow-up time was right-censored on April 28, 2020 so that each patient had at least 28 days of observation.
Between March 2 and April 1, 2020, 1150 adults were admitted to both hospitals with laboratory-confirmed COVID-19, of which 257 (22%) were critically ill. The median age of patients was 62 years (IQR 51–72), 171 (67%) were men. 212 (82%) patients had at least one chronic illness, the most common of which were hypertension (162 63%) and diabetes (92 36%). 119 (46%) patients had obesity. As of April 28, 2020, 101 (39%) patients had died and 94 (37%) remained hospitalised. 203 (79%) patients received invasive mechanical ventilation for a median of 18 days (IQR 9–28), 170 (66%) of 257 patients received vasopressors and 79 (31%) received renal replacement therapy. The median time to in-hospital deterioration was 3 days (IQR 1–6). In the multivariable Cox model, older age (adjusted hazard ratio aHR 1·31 1·09–1·57 per 10-year increase), chronic cardiac disease (aHR 1·76 1·08–2·86), chronic pulmonary disease (aHR 2·94 1·48–5·84), higher concentrations of interleukin-6 (aHR 1·11 95%CI 1·02–1·20 per decile increase), and higher concentrations of D-dimer (aHR 1·10 1·01–1·19 per decile increase) were independently associated with in-hospital mortality.
Critical illness among patients hospitalised with COVID-19 in New York City is common and associated with a high frequency of invasive mechanical ventilation, extrapulmonary organ dysfunction, and substantial in-hospital mortality.
National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, National Institutes of Health, and the Columbia University Irving Institute for Clinical and Translational Research.
The SARS-CoV-2 Omicron BA.1 variant emerged in 2021
and has multiple mutations in its spike protein
. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with ...Delta, and a marked change in its antigenicity increases Omicron's evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways
demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis.
Here, we present FissionNet, a proteome-wide binary protein interactome for S. pombe, comprising 2,278 high-quality interactions, of which ∼50% were previously not reported in any species. FissionNet ...unravels previously unreported interactions implicated in processes such as gene silencing and pre-mRNA splicing. We developed a rigorous network comparison framework that accounts for assay sensitivity and specificity, revealing extensive species-specific network rewiring between fission yeast, budding yeast, and human. Surprisingly, although genes are better conserved between the yeasts, S. pombe interactions are significantly better conserved in human than in S. cerevisiae. Our framework also reveals that different modes of gene duplication influence the extent to which paralogous proteins are functionally repurposed. Finally, cross-species interactome mapping demonstrates that coevolution of interacting proteins is remarkably prevalent, a result with important implications for studying human disease in model organisms. Overall, FissionNet is a valuable resource for understanding protein functions and their evolution.
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•A proteome-wide network of 2,278 high-quality binary S. pombe protein interactions•Species-specific interaction rewiring among yeasts and human•Gene duplication modes shape the functional fate of paralogous proteins•Cross-species interactome mapping uncovers extensive coevolution
FissionNet is a proteome-wide binary interactome network for S. pombe. Comparative analyses of FissionNet with protein networks in budding yeast and human reveal how protein networks evolve, principles of gene repurposing following duplication, and insights into species-specific alterations of function.
The archaeological record of Africa provides the earliest evidence for the emergence of the complex symbolic and technological behaviours that characterize Homo sapiens
. The coastal setting of many ...archaeological sites of the Late Pleistocene epoch, and the abundant shellfish remains recovered from them, has led to a dominant narrative in which modern human origins in southern Africa are intrinsically tied to the coast and marine resources
, and behavioural innovations in the interior lag behind. However, stratified Late Pleistocene sites with good preservation and robust chronologies are rare in the interior of southern Africa, and the coastal hypothesis therefore remains untested. Here we show that early human innovations that are similar to those dated to around 105 thousand years ago (ka) in coastal southern Africa existed at around the same time among humans who lived over 600 km inland. We report evidence for the intentional collection of non-utilitarian objects (calcite crystals) and ostrich eggshell from excavations of a stratified rockshelter deposit in the southern Kalahari Basin, which we date by optically stimulated luminescence to around 105 ka. Uranium-thorium dating of relict tufa deposits indicates sporadic periods of substantial volumes of fresh, flowing water; the oldest of these episodes is dated to between 110 and 100 ka and is coeval with the archaeological deposit. Our results suggest that behavioural innovations among humans in the interior of southern Africa did not lag behind those of populations near the coast, and that these innovations may have developed within a wet savannah environment. Models that tie the emergence of behavioural innovations to the exploitation of coastal resources by our species may therefore require revision.
Harmonizing cell types across the single-cell community and assembling them into a common framework is central to building a standardized Human Cell Atlas. Here, we present CellHint, a predictive ...clustering tree-based tool to resolve cell-type differences in annotation resolution and technical biases across datasets. CellHint accurately quantifies cell-cell transcriptomic similarities and places cell types into a relationship graph that hierarchically defines shared and unique cell subtypes. Application to multiple immune datasets recapitulates expert-curated annotations. CellHint also reveals underexplored relationships between healthy and diseased lung cell states in eight diseases. Furthermore, we present a workflow for fast cross-dataset integration guided by harmonized cell types and cell hierarchy, which uncovers underappreciated cell types in adult human hippocampus. Finally, we apply CellHint to 12 tissues from 38 datasets, providing a deeply curated cross-tissue database with ∼3.7 million cells and various machine learning models for automatic cell annotation across human tissues.
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