Notes

Temporary focus uniquely increases target characteristics.
The type I interferons (type I IFNs) are central to a vast array of immunological functions. The production of these immune-modulatory molecules is initiated at the early stages of the innate immune responses and, therefore, plays a dominant role in shaping downstream events in both innate and adaptive immunity. Indeed, the major role of IFNα/β is the induction of priming states, relevant for the functional differentiation of T lymphocyte subsets. Among T cell subtypes, the CD4 +CD25 +Foxp3 + T regulatory cells (Tregs) represent a specialized subset of CD4 + T cells with a critical role in maintaining peripheral tolerance and immune homeostasis. Although the role of type I IFNs in maintaining the function of thymus-derived Tregs has been previously described, the direct contribution of these innate factors to peripheral Treg (pTreg) and induced Treg (iTreg) differentiation and suppressive function is still unclear. We now show that, under tolerogenic conditions, IFNα/β play a critical role in antigen-specific and also polyclonal naïve CD4 + T cell conversion into peripheral antigen-specific CD4 +CD25 +Foxp3 + Tregs and inhibit CD4 + T helper (Th) cell expansion in mice. While type I IFNs sustain the expression and the activation of the transcription master regulators Foxp3, Stat3 and Stat5, these innate molecules reciprocally inhibit Th17 cell differentiation. Altogether, these results indicate a new pivotal role of IFNα/β on pTreg differentiation and induction of peripheral tolerance, which may have important implications in the therapeutic control of inflammatory disorders, such as of autoimmune diseases.
Infections caused by multidrug-resistant pathogens such as Acinetobacter baumannii constitute a major health problem worldwide. In this study we present a global in vivo transcriptomic analysis of A. baumannii isolated from the lungs of mice with pneumonia infection.

Mice were infected with A. baumannii ATCC 17978 and AbH12O-A2 strains and the total bacterial RNA was analyzed by RNA-seq. IκB inhibitor Lists of differentially expressed genes were obtained and 14 of them were selected for gene deletion and further analysis.

Transcriptomic analysis revealed a specific gene expression profile in A. baumannii during the lung infection with up-regulation of genes involved in iron acquisition and host invasion. Mutant strains lacking the feoA, mtnN, yfgC, basB, hisF, oatA and bfnL showed a significant loss of virulence in murine pneumonia. A decrease in biofilm formation, adherence to human epithelial cells and growth rate was observed in some mutants.

This study provides an insight into the A. baumannii gene expression profile during the murine pneumonia infection. Data revealed that 7 in vivo up-regulated genes were involved in virulence, and could be considered new therapeutic targets.
This study provides an insight into the A. baumannii gene expression profile during the murine pneumonia infection. Data revealed that 7 in vivo up-regulated genes were involved in virulence, and could be considered new therapeutic targets.
Despite the progress made in studying protein-ligand interactions and the widespread application of docking and affinity prediction tools, improving their precision and efficiency still remains a challenge. Computational approaches based on the scoring of docking conformations with statistical potentials constitute a popular alternative to more accurate but costly physics-based thermodynamic sampling methods. In this context, a minimalist and fast sidechain-free knowledge-based potential with a high docking and screening power can be very useful when screening a big number of putative docking conformations.

Here we present a novel coarse-grained potential defined by a 3D joint probability distribution function that only depends on the pairwise orientation and position between protein backbone and ligand atoms. Despite its extreme simplicity, our approach yields very competitive results with the state-of-the-art scoring functions, especially in docking and screening tasks. For example, we observed a two-fold improvement in the median 5% enrichment factor on the DUD-E benchmark compared to Autodock Vina results. Moreover, our results prove that a coarse sidechain-free potential is sufficient for a very successful docking pose prediction.

The standalone version of KORP-PL with the corresponding tests and benchmarks are available at https//team.inria.fr/nano-d/korp-pl/ and https//chaconlab.org/modeling/korp-pl.

Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.Limonene, a valuable cyclic monoterpene, has been broadly studied in recent decades due to its wide application in the food, cosmetics and pharmaceutical industries. Engineering of the yeast Yarrowia lipolytica for fermentation of renewable biomass lignocellulosic hydrolysate may reduce the cost and improve the economics of bioconversion for the production of limonene. The aim of this study was to engineer Y. lipolytica to produce limonene from xylose and low-cost lignocellulosic feedstock. The heterologous genes XR and XDH and native gene XK encoding xylose assimilation enzymes, along with the heterologous genes tNDPS1 and tLS encoding orthogonal limonene biosynthetic enzymes, were introduced into the Po1f strain to facilitate xylose fermentation to limonene. The initially developed strain produced 0.44 mg/L of limonene in 72 h with 20 g/L of xylose. Overexpression of genes from the mevalonate pathway, including HMG1 and ERG12, significantly increased limonene production from xylose to ∼9.00 mg/L in 72 h. Furthermore, limonene production peaked at 20.57 mg/L with 50% hydrolysate after 72 h when detoxified lignocellulosic hydrolysate was used. This study is the first to report limonene production by yeast from lignocellulosic feedstock, and these results indicate the initial steps toward economical and sustainable production of isoprenoids from renewable biomass by engineered Y. lipolytica.
Lysine rich foods such as milk and legumes serve as important food additions to the lysine deficient cereal-based diets of vegetarian populations in low- and middle-income countries (LMICs) to alleviate the risk of quality corrected dietary protein inadequacy. Dietary protein quality can be determined by estimating the metabolic availability (MA) of lysine.

The study aimed to estimate the MA of lysine in spray-dried cow milk powder (SMP), heat-treated spray-dried cow milk powder (HSMP), and a habitually consumed cereal-legume based vegetarian meal (VM), using the indicator amino acid oxidation (IAAO) slope-ratio method.

The MA of lysine in SMP, HSMP, and VM was estimated in 7 healthy young men aged 19-24 y with BMI of 21.5±0.5kg/m2 in a repeated measures design. The IAAO response slopes with 2 graded lysine intakes (10.5 and 15.0 mg·kg-1·d-1) from the SMP and VM were compared with the response slope generated with 3 graded crystalline lysine intakes (6.0, 10.5, and 15.0 mg·kg-1·d-1) at the subrequiremeny processed legumes and milk powder, to meet the protein requirement. This trial was registered at Clinical Trials Registry of India (http//ctri.nic.in) as CTRI/2019/08/020568.We reported two fatal cases of acute liver failure secondary to Herpes Simplex Virus 1 infection in COVID-19 patients, following tocilizumab and corticosteroid therapy.Screening for and prompt recognition of Herpes Simplex Virus 1 reactivation in these patients, undergoing immunomodulatory treatment, may have potentiallyrelevant clinical consequences.In microbial corrinoid-dependent methyltransferase systems, adventitious Co(I)-corrinoid oxidation halts catalysis and necessitates repair by ATP-dependent reductive activases. RamA, an activase with a C-terminal ferredoxin domain with two [4Fe-4S] clusters from methanogenic archaea, has been far less studied than the bacterial activases bearing an N-terminal ferredoxin domain with one [2Fe-2S] cluster. These differences suggest RamA might prove to have other distinctive characteristics. Here, we examine RamA kinetics and the stoichiometry of the corrinoid proteinRamA complex. Like bacterial activases, K+ stimulates RamA. Potassium stimulation had been questioned due to differences in the primary structure of bacterial and methanogen activases. Unlike one bacterial activase, ATP is not inhibitory allowing the first determination of apparent kinetic parameters for any corrinoid activase. Unlike bacterial activases, a single RamA monomer complexes a single corrinoid protein monomer. Alanine replacement of a RamA serine residue corresponding to the serine of one bacterial activase which ligates the corrinoid cobalt during complex formation led to only moderate changes in the kinetics of RamA. These results reveal new differences in the two types of corrinoid activases, and provide direct evidence for the proposal that corrinoid activases act as catalytic monomers, unlike other enzymes that couple ATP hydrolysis to difficult reductions.Economic yield loss and reduction in grain quality from brown stink bug, Euschistus servus (Say), feeding injury in early and late stages of maize, Zea mays (Poales Poaceae, Linnaeus), development was assessed in Virginia and North Carolina in 2018 and 2019. Varying levels of stink bug infestations were introduced to seedling maize (V2-early stage), and a range of late-stages of maize, including 1) the last stage of vegetative development (V12/V14), 2) prior to tasseling, 3) at tasseling (VT), and 4) across all tested late growth stages. Euschistus servus infestation levels included 33, 67, and 100% of maize seedlings, and 25, 50, 100, and 200% of plants during later stages. Infestations were maintained on seedling maize for 7 d, and 8 or 16 d in reproductive stages. Infestation level in seedling maize had an impact on grain yield. Infestation level and growth stage both had an impact on grain yield in reproductive maize. The percentage of discolored kernels was also affected by infestation level, but not growth stage. Regression analysis between grain yield and infestation level indicated that the average economic injury level is 7% in seedling maize (7 bugs/100 plants) and 12% (12 bugs/100 plants) from the last vegetative stages (V12/V14) through pollination (VT). The economic injury level in the late vegetative stages is only applicable when infestations are present for an extended period of time (16 d), emphasizing the need for continued scouting of maize throughout the season to make informed management decisions.
Quality control (QC) is a critical step in single-cell RNA-seq (scRNA-seq) data analysis. Low-quality cells are removed from the analysis during the QC process to avoid misinterpretation of the data. One of important QC metrics is the mitochondrial proportion (mtDNA%), which is used as a threshold to filter out low-quality cells. Early publications in the field established a threshold of 5% and since then, it has been used as a default in several software packages for scRNA-seq data analysis, and adopted as a standard in many scRNA-seq studies. However, the validity of using a uniform threshold across different species, single-cell technologies, tissues, and cell types has not been adequately assessed.

We systematically analyzed 5,530,106 cells reported in 1,349 annotated datasets available in the PanglaoDB database and found that the average mtDNA% in scRNA-seq data across human tissues is significantly higher than in mouse tissues. This difference is not confounded by the platform used to generate the data.
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