Mcmanusmclaughlin3511

Antibody-mediated immune responses rely on antigen recognition by the B cell antigen receptor (BCR) and the proper engagement of its intracellular signal effector proteins. Src homology (SH) 2 domain-containing leukocyte protein of 65 kDa (SLP65) is the key scaffold protein mediating BCR signaling. In resting B cells, SLP65 colocalizes with Cbl-interacting protein of 85 kDa (CIN85) in cytoplasmic granules whose formation is not fully understood. Here we show that effective B cell activation requires tripartite phase separation of SLP65, CIN85, and lipid vesicles into droplets via vesicle binding of SLP65 and promiscuous interactions between nine SH3 domains of the trimeric CIN85 and the proline-rich motifs (PRMs) of SLP65. Vesicles are clustered and the dynamical structure of SLP65 persists in the droplet phase in vitro. Our results demonstrate that phase separation driven by concerted transient interactions between scaffold proteins and vesicles is a cellular mechanism to concentrate and organize signal transducers.This paper presents the Plug-Load Appliance Identification Dataset (PLAID), a labelled dataset containing records of the electrical voltage and current of domestic electrical appliances obtained at a high sampling frequency (30 kHz). The dataset contains 1876 records of individually-metered appliances from 17 different appliance types (e.g., refrigerators, microwave ovens, etc.) comprising 330 different makes and models, and collected at 65 different locations in Pittsburgh, Pennsylvania (USA). Additionally, PLAID contains 1314 records of the combined operation of 13 of these appliance types (i.e., measurements obtained when multiple appliances were active simultaneously). Identifying electrical appliances based on electrical measurements is of importance in demand-side management applications for the electrical power grid including automated load control, load scheduling and non-intrusive load monitoring. This paper provides a systematic description of the measurement setup and dataset so that it can be used to develop and benchmark new methods in these and other applications, and so that extensions to it can be developed and incorporated in a consistent manner.Current antibiotics cannot eradicate uropathogenic Escherichia coli (UPEC) biofilms, leading to recurrent urinary tract infections. Here, we show that the insect antimicrobial peptide cecropin A (CecA) can destroy planktonic and sessile biofilm-forming UPEC cells, either alone or when combined with the antibiotic nalidixic acid (NAL), synergistically clearing infection in vivo without off-target cytotoxicity. The multi-target mechanism of action involves outer membrane permeabilization followed by biofilm disruption triggered by the inhibition of efflux pump activity and interactions with extracellular and intracellular nucleic acids. These diverse targets ensure that resistance to the CecA + NAL combination emerges slowly. The antimicrobial mechanisms of CecA, thus, extend beyond pore-forming activity to include an unanticipated biofilm-eradication process, offering an alternative approach to combat antibiotic-resistant UPEC infections.A better control over processes responsible for the photocurrent generation in semiconductors and nanocomposites is essential in the fabrication of photovoltaic devices, efficient photocatalysts and optoelectronic elements. Therefore, new approaches towards photochemical properties tuning are intensively searched for. Among numerous parameters, the photocurrent polarity is of great importance to the overall performance of a device. Usually, the polarity is controlled through an alignment of electronic states/bands, tailoring of applied potential or suitable selection of incident light wavelengths. In most scenarios though, the influence of light intensity is somehow neglected and either some arbitrarily chosen, natural conditions are mimicked or this parameter is varied only in a narrow range. Here we present a ternary nanocomposite in which the persistent photocurrent polarity switching is achieved through changes in the light intensity. We also present arguments suggesting this behaviour is of a general character and should be considered also in other photochemical systems.Laser spectroscopy outperforms electrochemical and semiconductor gas sensors in selectivity and environmental survivability. However, the performance of the state-of-the-art laser sensors is still insufficient for many high precision applications. Here, we report mode-phase-difference photothermal spectroscopy with a dual-mode anti-resonant hollow-core optical fiber and demonstrate all-fiber gas (acetylene) detection down to ppt (parts-per-trillion) and  less then 1% instability over a period of 3 hours. An anti-resonant hollow-core fiber could be designed to transmit light signals over a broad wavelength range from visible to infrared, covering molecular absorption lines of many important gases. This would enable multi-component gas detection with a single sensing element and pave the way for ultra-precision gas sensing for medical, environmental and industrial applications.Meiotic recombination is initiated by SPO11-induced double-strand breaks (DSBs). PRT062070 chemical structure In most mammals, the methyltransferase PRDM9 guides SPO11 targeting, and the ATM kinase controls meiotic DSB numbers. Following MRE11 nuclease removal of SPO11, the DSB is resected and loaded with DMC1 filaments for homolog invasion. Here, we demonstrate the direct detection of meiotic DSBs and resection using END-seq on mouse spermatocytes with low sample input. We find that DMC1 limits both minimum and maximum resection lengths, whereas 53BP1, BRCA1 and EXO1 play surprisingly minimal roles. Through enzymatic modifications to END-seq, we identify a SPO11-bound meiotic recombination intermediate (SPO11-RI) present at all hotspots. We propose that SPO11-RI forms because chromatin-bound PRDM9 asymmetrically blocks MRE11 from releasing SPO11. In Atm-/- spermatocytes, trapped SPO11 cleavage complexes accumulate due to defective MRE11 initiation of resection. Thus, in addition to governing SPO11 breakage, ATM and PRDM9 are critical local regulators of mammalian SPO11 processing.