Hybridization is suggested to contribute to ecomorphological and taxonomic diversity in lacustrine East African cichlids. This is supported by studies demonstrating that genetic diversity within lake ...radiations has been influenced by hybridization events, leading to extensive phenotypic differentiation of genetically closely related species. Hybrid persistence and speciation in sympatry with gene flow can be explained by pleiotropy in traits involved in reproductive isolation; however, little attention has been given to how trait differentiation is established during hybrid ontogeny, and how this may relate to trophic and locomotor specialization. This study compares body shape changes in a Lake Victoria cichlid hybrid throughout its post‐hatch ontogeny to those of its parental species. Across the considered age/size categories, hybrids occupy a distinct and intermediate morphological space, yet where several transgressive traits emerge. A between‐group principal component analysis on body shapes across size categories reveals axes of shape variation exclusive to the hybrids in the youngest/smallest size categories. Shape differences in the hybrids involved morphological traits known to be implicated in trophic and locomotor specializations in the parental species. Combined, our findings suggest that phenotypic divergence in the hybrid can lead to functional differences that may potentially release them to some degree from competition with the parental species. These findings agree with recent literature that addresses the potential importance of hybridization for the unusually recent origin of the Lake Victoria cichlid super‐species flock.
Wireframe illustrating the unique axis of shape variation exclusive to size category I H. fischeri – H. piceatus hybrids. Shape differences involve variation in functionally‐relevant trophic (e.g. gape inclination) and locomotor (e.g. postcranial body streamline) morphological specializations.
Advances in the understanding of lipid droplet biology have revealed essential roles for these organelles in mediating proper cellular homeostasis and stress response. Lipid droplets were initially ...thought to play a passive role in energy storage. However, recent studies demonstrate that they have substantially broader functions, including protection from reactive oxygen species, endoplasmic reticulum stress, and lipotoxicity. Dysregulation of lipid droplet homeostasis is associated with various pathologies spanning neurological, metabolic, cardiovascular, oncological, and renal diseases. This review provides an overview of the current understanding of lipid droplet biology in both health and disease.
Functional gastrointestinal disorders (FGIDs) are characterized by chronic complaints arising from disorganized brain-gut interactions leading to dysmotility and hypersensitivity. The two most ...prevalent FGIDs, affecting up to 16-26% of worldwide population, are functional dyspepsia and irritable bowel syndrome. Their etiopathogenic mechanisms remain unclear, however, recent observations reveal low-grade mucosal inflammation and immune activation, in association with impaired epithelial barrier function and aberrant neuronal sensitivity. These findings come to challenge the traditional view of FGIDs as pure functional disorders, and relate the origin to a tangible organic substrate. The mucosal inflammatory infiltrate is dominated by mast cells, eosinophils and intraepithelial lymphocytes in the intestine of FGIDs. It is well established that mast cell activation can generate epithelial and neuro-muscular dysfunction and promote visceral hypersensitivity and altered motility patterns in FGIDs, postoperative ileus, food allergy and inflammatory bowel disease. This review will discuss the role of mucosal mast cells in the gastrointestinal tract with a specific focus on recent advances in disease mechanisms and clinical management in irritable bowel syndrome and functional dyspepsia.
Impact of COVID‐19 on pacemaker implant Gonzales‐Luna, Ana C.; Torres‐Valencia, Javier O.; Alarcón‐Santos, Javier E. ...
Journal of arrhythmia,
October 2020, Letnik:
36, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Objectives
The purpose of this article was to determine the change in the volume of pacemaker implantations with the COVID‐2019 pandemic and to assess the change in the number of pacemaker implants ...according to etiology during the pandemic.
Background
The establishment of a mandatory social isolation have generated a decrease in activities in cardiology units.
Methods
Descriptive, cross‐sectional study that used a database of a Peruvian Hospital. Time was divided into three categories: Before COVID period and COVID period including Previous to Social isolation (SI) and Social Isolation. The number of pacemaker implantations were compared per the same amount of time.
Results
A reduction in the pacemaker implant of 73% (95% CI: 33‐113; P < .001) was observed during the COVID‐19 pandemic period, and a reduction of 78% of patients with the diagnosis of complete or high‐grade atrioventricular block and a reduction in the de‐novo pacemaker implant was observed, regardless of the etiology.
Conclusions
Our results indicate a very significant reduction (73%) in de‐novo pacemaker implantation during the months of the COVID‐19 pandemic. The reduction in the number of de‐novo pacemaker occurred independent of the etiology.
This article reports the reduction of de‐novo pacemaker implants in a Peruvian hospital due to the COVID‐19 pandemic. The reduction in the number of de‐novo pacemaker occurred independently of the etiology.
Predicting the spatial configuration of gas in nanopores of is relevant in applications such as fluid flow forecasting and hydrocarbon reserves estimation. For example, shale reservoirs have suffered ...from computationally intractable multiscale problems, since fluid properties such as viscosity, density, and adsorption must be calculated by using expensive molecular dynamics (MD) simulations within each nanopore, whereas flow through these connected nanopores must be simulated at the micrometer scale. We utilize machine learning techniques to quickly and accurately model nanoscale confinement effects as an important step toward bridging the nano and micro scales. Our workflow is based on building and training physics-based deep-neural-networks models by learning from a database of MD calculations. The model accounts for the adsorption phenomenon by predicting the statistical distribution of gas inside nanopores. Because large databases of MD calculations are expensive to create, we investigate active learning (AL) as a data set construction strategy. In this workflow, new data are selected based on the model uncertainty via the query-by-committee approach. We show that our workflow obtains accurate models that generalize to real scanning electron microscopy geometries with 1/10th of the number of MD calculations required vs random data set generation. Our method enables the possibility of modeling nanoconfinement effects at the mesoscale, where complex connected sets of nanopores affect flow.
While it is known that energy efficiency (EE) lowers power sector demand and emissions, study of the air quality and public health impacts of EE has been limited. Here, we quantify the air quality ...and mortality impacts of a 12% summertime (June, July, and August) reduction in baseload electricity demand. We use the AVoided Emissions and geneRation Tool (AVERT) to simulate plant-level generation and emissions, the Community Multiscale Air Quality (CMAQ) model to simulate air quality, and the Environmental Benefits Mapping and Analysis Program (BenMAP) to quantify mortality impacts. We find EE reduces emissions of NO x by 13.2%, SO2 by 12.6%, and CO2 by 11.6%. On a nationwide, summer average basis, ambient PM2.5 is reduced 0.55% and O3 is reduced 0.45%. Reduced exposure to PM2.5 avoids 300 premature deaths annually (95% CI: 60 to 580) valued at $2.8 billion ($0.13 billion to $9.3 billion), and reduced exposure to O3 averts 175 deaths (101 to 244) valued at $1.6 billion ($0.15 billion to $4.5 billion). This translates into a health savings rate of $0.049/kWh ($0.031/kWh for PM2.5 and $0.018/kWh for O3). These results illustrate the importance of capturing the health benefits of EE and its potential as a strategy to achieve air standards.
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are anti-hyperglycemic agents that prevent glucose reabsorption in proximal tubular cells. SGLT2i improves renal outcomes in both diabetic and ...non-diabetic patients, indicating it may have beneficial effects beyond glycemic control. Here, we demonstrate that SGLT2i affects energy metabolism and podocyte lipotoxicity in experimental Alport syndrome (AS). In vitro, we found that the SGLT2 protein was expressed in human and mouse podocytes to a similar extent in tubular cells. Newly established immortalized podocytes from Col4a3 knockout mice (AS podocytes) accumulate lipid droplets along with increased apoptosis when compared to wild-type podocytes. Treatment with SGLT2i empagliflozin reduces lipid droplet accumulation and apoptosis in AS podocytes. Empagliflozin inhibits the utilization of glucose/pyruvate as a metabolic substrate in AS podocytes but not in AS tubular cells. In vivo, we demonstrate that empagliflozin reduces albuminuria and prolongs the survival of AS mice. Empagliflozin-treated AS mice show decreased serum blood urea nitrogen and creatinine levels in association with reduced triglyceride and cholesterol ester content in kidney cortices when compared to AS mice. Lipid accumulation in kidney cortices correlates with a decline in renal function. In summary, empagliflozin reduces podocyte lipotoxicity and improves kidney function in experimental AS in association with the energy substrates switch from glucose to fatty acids in podocytes.
Impaired cellular cholesterol efflux is a key factor in the progression of renal, cardiovascular, and autoimmune diseases. Here we describe a class of 5-arylnicotinamide compounds, identified through ...phenotypic drug discovery, that upregulate ABCA1-dependent cholesterol efflux by targeting Oxysterol Binding Protein Like 7 (OSBPL7). OSBPL7 was identified as the molecular target of these compounds through a chemical biology approach, employing a photoactivatable 5-arylnicotinamide derivative in a cellular cross-linking/immunoprecipitation assay. Further evaluation of two compounds (Cpd A and Cpd G) showed that they induced ABCA1 and cholesterol efflux from podocytes in vitro and normalized proteinuria and prevented renal function decline in mouse models of proteinuric kidney disease: Adriamycin-induced nephropathy and Alport Syndrome. In conclusion, we show that small molecule drugs targeting OSBPL7 reveal an alternative mechanism to upregulate ABCA1, and may represent a promising new therapeutic strategy for the treatment of renal diseases and other disorders of cellular cholesterol homeostasis.
Multiphase flow properties of fractures are important in engineering applications such as hydraulic fracturing, evaluating the sealing capacity of caprocks, and the productivity of ...hydrocarbon-bearing tight rocks. Due to the computational requirements of high fidelity simulations, investigations of flow and transport through fractures typically rely on simplified assumptions applied to large fracture networks. These simplifications ignore the effect of pore-scale capillary phenomena and 3D realistic fracture morphology (for instance, tortuosity, contact points, and crevasses) that lead to macro-scale effective transport properties. The effect of these properties can be studied through lattice Boltzmann simulations, but they require high performance computing clusters and are generally limited in their domain size. In this work, we develop a technique to represent 3D fracture geometries and fluid distributions in 2D without losing any information. Using this innovative approach, we present a specialized machine learning model which only requires a few simulations for training but still accurately predicts fluid flow through 3D fractures. We demonstrate our technique using simulations of a water filled fracture being displaced by supercritical CO2. By generating highly efficient simulations of micro-scale multiphase flow in fractures, we hope to investigate a wide range of fracture types and generalize our method to be incorporated into larger discrete fracture network simulations.
Synthetic gene circuits allow us to govern cell behavior in a programmable manner, which is central to almost any application aiming to harness engineered living cells for user-defined tasks. ...Transcription factors (TFs) constitute the 'classic' tool for synthetic circuit construction but some of their inherent constraints, such as insufficient modularity, orthogonality and programmability, limit progress in such forward-engineering endeavors. Here we review how CRISPR (clustered regularly interspaced short palindromic repeats) technology offers new and powerful possibilities for synthetic circuit design. CRISPR systems offer superior characteristics over TFs in many aspects relevant to a modular, predictable and standardized circuit design. Thus, the choice of CRISPR technology as a framework for synthetic circuit design constitutes a valid alternative to complement or replace TFs in synthetic circuits and promises the realization of more ambitious designs.
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