Unusual Regulation of a Leaderless Operon Involved in the Catabolism of Dimethylsulfoniopropionate in Rhodobacter sphaeroides

Rhodobacter sphaeroides strain 2.4.1 is a widely studied bacterium that has recently been shown to cleave the abundant marine anti-stress molecule dimethylsulfoniopropionate (DMSP) into acrylate plus gaseous dimethyl sulfide. It does so by using a lyase encoded by dddL, the promoter-distal gene of a three-gene operon, acuR-acuI-dddL. Transcription of the operon was enhanced when cells were pre-grown with the substrate DMSP, but this induction is indirect, and requires the conversion of DMSP to the product acrylate, the bona fide co-inducer. This regulation is mediated by the product of the promoter-proximal gene acuR, a transcriptional regulator in the TetR family. AcuR represses the operon in the absence of acrylate, but this is relieved by the presence of the co-inducer. Another unusual regulatory feature is that the acuR-acuI-dddL mRNA transcript is leaderless, such that acuR lacks a Shine-Dalgarno ribosomal binding site and 5′-UTR, and is translated at a lower level compared to the downstream genes. This regulatory unit may be quite widespread in bacteria, since several other taxonomically diverse lineages have adjacent acuR-like and acuI-like genes; these operons also have no 5′ leader sequences or ribosomal binding sites and their predicted cis-acting regulatory sequences resemble those of R. sphaeroides acuR-acuI-dddL

Prebiotic and Probiotic Fortified Milk in Prevention of Morbidities among Children: Community-Based, Randomized, Double-Blind, Controlled Trial

HN019 to milk, in preventing diarrhea, respiratory infections and severe illnesses, in children aged 1–4 years as part of a four group study design, running two studies simultaneously. HN019 (PP; n = 312). Children were followed up for 1 year providing data for 1–4 years. Biweekly household surveillance was conducted to gather information on compliance and morbidity. Both study groups were comparable at baseline; compliance to intervention was similar. Overall, there was no effect of prebiotic and probiotic on diarrhea (6% reduction, 95% Confidence Interval [CI]: −1 to 12%; p = 0.08). Incidence of dysentery episodes was reduced by 21% (95% CI: 0 to 38%; p = 0.05). Incidence of pneumonia was reduced by 24% (95% CI: 0 to 42%; p = 0.05) and severe acute lower respiratory infection (ALRI) by 35% (95% CI: 0 to 58%; p = 0.05). Compared to children in Co group, children in PP group had 16% (95% CI: 5 to 26%, p = 0.004) and 5% (95% CI: 0 to 10%; p = 0.05) reduction in days with severe illness and high fever respectively.Milk can be a good medium for delivery of prebiotic and probiotic and resulted in significant reduction of dysentery, respiratory morbidity and febrile illness. Overall, impact of diarrhea was not significant. These findings need confirmation in other settings

CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10–driven MARCH1-mediated ubiquitination and degradation

By opposing IL-10–driven, MARCH1-mediated ubiquitination and degradation of MHC class II, CD83 may boost the immunogenicity of dendritic cells

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Search for CP Violation in D-s(+) -> K-S(0)pi(+), D+ -> (KSK+)-K-0, and D+ -> phi pi(+) Decays

A search for charge-parity ($CP$) violation in Cabibbo-suppressed $D_s^+\to K_S^0 \pi^+$, $D^+\to K_S^0 K^+$ and $D^+\to \phi \pi^+$ decays is reported using proton-proton collision data, corresponding to an integrated luminosity of 3.8 fb$^{-1}$, collected at a center-of-mass energy of 13 TeV with the LHCb detector. High-yield samples of kinematically and topologically similar Cabibbo-favored $D_{(s)}^+$ decays are analyzed to subtract nuisance asymmetries due to production and detection effects, including those induced by $CP$ violation in the neutral kaon system. The results are \begin{align*} \mathcal{A}_{CP}(D_s^+\to K_S^0 \pi^+) &=\left(\phantom{-}1.3\phantom{0}\pm1.9\phantom{0}\pm0.5\phantom{0}\right)\times10^{-3},\\ \mathcal{A}_{CP}(D^+\to K_S^0 K^+) &=\left(-0.09\pm0.65\pm0.48\right)\times10^{-3},\\ \mathcal{A}_{CP}(D^+\to \phi \pi^+) &=\left(\phantom{-}0.05\pm0.42\pm0.29\right)\times10^{-3}, \end{align*} where the first uncertainties are statistical and the second systematic. They are the most precise measurements of these quantities to date, and are consistent with $CP$ symmetry.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2019-002.htm

Observation of the Λb0 → χc1 (3872) pK− decay

No abstract available

Search for the lepton-flavor-violating decays Bs0→τ±μ∓ and B0→τ±μ∓

Results are reported from a search for the rare decays B 0 s → τ ± μ ∓ and B 0 → τ ± μ ∓ , where the τ lepton is reconstructed in the channel τ − → π − π + π − ν τ . These processes are effectively forbidden in the standard model, but they can potentially occur at detectable rates in models of new physics that can induce lepton-flavor-violating decays. The search is based on a data sample corresponding to 3     fb − 1 of proton-proton collisions recorded by the LHCb experiment in 2011 and 2012. The event yields observed in the signal regions for both processes are consistent with the expected standard model backgrounds. Because of the limited mass resolution arising from the undetected τ neutrino, the B 0 s and B 0 signal regions are highly overlapping. Assuming no contribution from B 0 → τ ± μ ∓ , the upper limit B ( B 0 s → τ ± μ ∓ ) < 4.2 × 10 − 5 is obtained at 95% confidence level. If no contribution from B 0 s → τ ± μ ∓ is assumed, a limit of B ( B 0 → τ ± μ ∓ ) < 1.4 × 10 − 5 is obtained at 95% confidence level. These results represent the first limit on B ( B 0 s → τ ± μ ∓ ) and the most stringent limit on B ( B 0 → τ ± μ ∓ )

Precision measurement of the Ξcc++Ξcc++ {\varXi}_{cc}^{++} mass

A measurement of the Ξ++cc mass is performed using data collected by the LHCb experiment between 2016 and 2018 in pp collisions at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 5.6 fb−1. The Ξ++cc candidates are reconstructed via the decay modes Ξ++cc→Λ+cK−π+π+ and Ξ++cc→Ξ+cπ+. The result, 3621.55 ± 0.23 (stat) ± 0.30 (syst) MeV/c2, is the most precise measurement of the Ξ++cc mass to date