Infectious complications in acquired haemophilia A: Insights from the Spanish Registry (AHASR).

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Metabolic Engineering of Methanotrophic Bacteria for Production of Taxadiene from Methane.

The growing demand for natural products in pharmaceutical applications has prompted a focus on more sustainable methods to produce high-value terpenoids using microbial cell factories. Due to the characteristics of high abundance, renewable, and low cost, methane has emerged as a promising feedstock for biomanufacturing. In this study, the methanotrophic bacterium 5GB1C, known for its industrial potential, was metabolically engineered to synthesize taxadiene, a crucial precursor in paclitaxel production.

Protein Biosynthesis and Carbon Catabolite Repression Are Transcriptionally Upregulated in Saccharomyces cerevisiae by Extracellular Fractions From Several Wine Yeast Species.

Non-Saccharomyces yeast species are increasingly used in winemaking in combination with Saccharomyces cerevisiae to modulate sensory attributes or as processing aids. Consequently, there is academic and practical interest in understanding how different yeast species interact with each other in grape must. Although interactions will depend on the metabolic capabilities of the strains involved, there are other possible interaction mechanisms between wine yeasts.

Needle/electrode insertion device for measuring plant electrical signals.

Plants generate electrical signals in response to mild and severe environmental stimuli to transmit physiological information and ultimately trigger defensive responses during stressful events. It has been proposed that detecting and characterizing such signals could allow researchers to mimic specific electrical stimuli and provoke desirable responses in crops. Nevertheless, manually inserting electrodes in plant tissues leads to irregular data records due to a lack of uniformity across insertion events.

The protein composition of human adenovirus replication compartments.

Human adenoviruses are double-stranded DNA viruses that replicate in the cell nucleus and induce the formation of replication compartments (RCs) that are critical in viral replication and control of virus-host interactions. RCs are specialized virus-induced subnuclear microenvironments where not only viral genome replication and expression are orchestrated but also host proteins that restrict viral replication are co-opted and subverted. The protein composition of these RCs remains largely unexplored.

A synthetic co-culture for bioproduction of ammonia from methane and air.

Unlabelled: Fixed nitrogen fertilizers feed 50% of the global population, but most fixed nitrogen production occurs using energy-intensive Haber-Bosch-based chemistry combining nitrogen (N2) from air with gaseous hydrogen (H2) from methane (CH4) at high temperatures and pressures in large-scale facilities sensitive to supply chain disruptions. This work demonstrates the biological transformation of atmospheric N2 into ammonia (NH3) using CH4 as the sole carbon and energy source in a single vessel at ambient pressure and temperature, representing a biological "room-pressure and room-temperature" route to NH3 that could ultimately be developed to support compact, remote, NH3 production facilities amenable to distributed biomanufacturing. The synthetic microbial co-culture of engineered methanotroph Methylomicrobium buryatense (now Methylotuvimicrobium buryatense) and diazotroph Azotobacter vinelandii converted three CH4 molecules to l-lactate (C3H6O3) and powered gaseous N2 conversion to NH3.

Metabolic engineering of Escherichia coli for the utilization of methylsuccinate, the product of methane activation via fumarate addition.

Methylsuccinate is a branched-chain, 5-carbon (C5) dicarboxylate that can be generated from the O-independent activation of methane via fumarate addition. However, no established metabolic pathway enables growth and product synthesis from methylsuccinate. Here, we report a synthetic pathway that converts methylsuccinate into two precursor metabolites: pyruvate and acetyl-CoA.

Author Correction: Predictive evolution of metabolic phenotypes using model-designed environments.

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Revealing reaction intermediates in one-carbon elongation by thiamine diphosphate/CoA-dependent enzyme family.

2-Hydroxyacyl-CoA lyase/synthase (HACL/S) is a thiamine diphosphate (ThDP)-dependent versatile enzyme originally discovered in the mammalian α-oxidation pathway. HACL/S natively cleaves 2-hydroxyacyl-CoAs and, in its reverse direction, condenses formyl-CoA with aldehydes or ketones. The one-carbon elongation biochemistry based on HACL/S has enabled the use of molecules derived from greenhouse gases as biomanufacturing feedstocks.

An Observational Study Suggests That Natural HAdV-36 Infection Decreases Blood Glucose Levels without Affecting Insulin Levels in Obese Young Subjects.

Human adenovirus-36 (HAdV-36) infection has been linked to obesity, low lipid levels, and improvements in blood glucose levels and insulin sensitivity in animal models and humans, although epidemiological studies remain controversial. Therefore, this study investigated the relationship between HAdV-36 seropositivity and glycemic control in youths. This observational study examined 460 youths (246 with normal weight and 214 obese subjects).

Metabolic flux optimization of iterative pathways through orthogonal gene expression control: Application to the β-oxidation reversal.

Balancing relative expression of pathway genes to minimize flux bottlenecks and metabolic burden is one of the key challenges in metabolic engineering. This is especially relevant for iterative pathways, such as reverse β-oxidation (rBOX) pathway, which require control of flux partition at multiple nodes to achieve efficient synthesis of target products. Here, we develop a plasmid-based inducible system for orthogonal control of gene expression (referred to as the TriO system) and demonstrate its utility in the rBOX pathway.

Reduction of ethanol content in wine with an improved combination of yeast strains and process conditions.

One interesting strategy to address the increasing alcohol content of wines, associated with climate change, is to reduce the ethanol yield during fermentation. Within this strategy, the approach that would allow the clearest reduction in alcohol content is the respiration of part of the grape sugars by yeasts. Non-Saccharomyces species can be used for this purpose but suffer from a limited ability to dominate the process and complete fermentation.

Engineering Escherichia coli for selective 1-decanol production using the reverse β-oxidation (rBOX) pathway.

1-Decanol has great value in the pharmaceutical and fragrance industries and plays an important role in the chemical industry. In this study, we engineered Escherichia coli to selectively synthesize 1-decanol by using enzymes of the core reverse β-oxidation (rBOX) pathway and termination module with overlapping chain-length specificity. Through screening for acyl-CoA reductase termination enzymes and proper regulation of rBOX pathway expression, a 1-decanol titer of 1.

Directed evolution of Saccharomyces cerevisiae for low volatile acidity during winemaking under aerobic conditions.

The use of yeast respiratory metabolism has been proposed as a promising approach to solve the problem of increasing ethanol content in wine, which is largely due to climate change. The use of S. cerevisiae for this purpose is mostly hampered by acetic acid overproduction generated under the necessary aerobic conditions.

Engineering a new-to-nature cascade for phosphate-dependent formate to formaldehyde conversion in vitro and in vivo.

Formate can be envisioned at the core of a carbon-neutral bioeconomy, where it is produced from CO by (electro-)chemical means and converted into value-added products by enzymatic cascades or engineered microbes. A key step in expanding synthetic formate assimilation is its thermodynamically challenging reduction to formaldehyde. Here, we develop a two-enzyme route in which formate is activated to formyl phosphate and subsequently reduced to formaldehyde.

Incorporating algorithmic uncertainty into a clinical machine deep learning algorithm for urgent head CTs.

Machine learning (ML) algorithms to detect critical findings on head CTs may expedite patient management. Most ML algorithms for diagnostic imaging analysis utilize dichotomous classifications to determine whether a specific abnormality is present. However, imaging findings may be indeterminate, and algorithmic inferences may have substantial uncertainty.

Childhood exposure to non-persistent endocrine disrupting chemicals and multi-omic profiles: A panel study.

Background: Individuals are exposed to environmental pollutants with endocrine disrupting activity (endocrine disruptors, EDCs) and the early stages of life are particularly susceptible to these exposures. Previous studies have focused on identifying molecular signatures associated with EDCs, but none have used repeated sampling strategy and integrated multiple omics. We aimed to identify multi-omic signatures associated with childhood exposure to non-persistent EDCs.

Saccharomyces cerevisiae responds similarly to co-culture or to a fraction enriched in Metschnikowia pulcherrima extracellular vesicles.

The recent introduction of non-conventional yeast species as companion wine starters has prompted a growing interest in microbial interactions during wine fermentation. There is evidence of interactions through interference and exploitation competition, as well as interactions depending on physical contact. Furthermore, the results of some transcriptomic analyses suggest interspecific communication, but the molecules or biological structures involved in recognition are not well understood.

Designing artificial pathways for improving chemical production.

Metabolic engineering exploits manipulation of catalytic and regulatory elements to improve a specific function of the host cell, often the synthesis of interesting chemicals. Although naturally occurring pathways are significant resources for metabolic engineering, these pathways are frequently inefficient and suffer from a series of inherent drawbacks. Designing artificial pathways in a rational manner provides a promising alternative for chemicals production.

Head CT deep learning model is highly accurate for early infarct estimation.

Non-contrast head CT (NCCT) is extremely insensitive for early (< 3-6 h) acute infarct identification. We developed a deep learning model that detects and delineates suspected early acute infarcts on NCCT, using diffusion MRI as ground truth (3566 NCCT/MRI training patient pairs). The model substantially outperformed 3 expert neuroradiologists on a test set of 150 CT scans of patients who were potential candidates for thrombectomy (60 stroke-negative, 90 stroke-positive middle cerebral artery territory only infarcts), with sensitivity 96% (specificity 72%) for the model versus 61-66% (specificity 90-92%) for the experts; model infarct volume estimates also strongly correlated with those of diffusion MRI (r > 0.

Tackling prediction uncertainty in machine learning for healthcare.

Predictive machine-learning systems often do not convey the degree of confidence in the correctness of their outputs. To prevent unsafe prediction failures from machine-learning models, the users of the systems should be aware of the general accuracy of the model and understand the degree of confidence in each individual prediction. In this Perspective, we convey the need of prediction-uncertainty metrics in healthcare applications, with a focus on radiology.

Global Transcriptome Analyses of Cellular and Viral mRNAs during HAdV-C5 Infection Highlight New Aspects of Viral mRNA Biogenesis and Cytoplasmic Viral mRNA Accumulations.

It is well established that human adenoviruses such as species C, types 2 and 5 (HAdV-C2 and HAdV-C5), induce a nearly complete shutoff of host-cell protein synthesis in the infected cell, simultaneously directing very efficient production of viral proteins. Such preferential expression of viral over cellular genes is thought to be controlled by selective nucleocytoplasmic export and translation of viral mRNA. While detailed knowledge of the regulatory mechanisms responsible for the translation of viral mRNA is available, the viral or cellular mechanisms of mRNA biogenesis are not completely understood.

Identifying the Main Drivers in Microbial Diversity for Cabernet Sauvignon Cultivars from Europe to South Africa: Evidence for a Cultivar-Specific Microbial Fingerprint.

Microbial diversity in vineyards and in grapes has generated significant scientific interest. From a biotechnological perspective, vineyard and grape biodiversity has been shown to impact soil, vine, and grape health and to determine the fermentation microbiome and the final character of wine. Thus, an understanding of the drivers that are responsible for the differences in vineyard and grape microbiota is required.

Adipocyte commitment of 3T3-L1 cells is required to support human adenovirus 36 productive replication concurrent with altered lipid and glucose metabolism.

Human adenovirus 36 (HAdV-D36) can cause obesity in animal models, induces an adipogenic effect and increased adipocyte differentiation in cell culture. HAdV-D36 infection alters gene expression and the metabolism of the infected cells resulting in increased glucose internalization and triglyceride accumulation. Although HAdV-D36 prevalence correlates with obesity in humans, whether human preadipocytes may be targeted has not been determined and metabolic reprogramming of preadipocytes has not been explored in the context of the viral replication cycle.