Davidporter5678

Top-down mass spectrometry has become the main method for intact proteoform identification, characterization, and quantitation. Because of the complexity of top-down mass spectrometry data, spectral deconvolution is an indispensable step in spectral data analysis, which groups spectral peaks into isotopic envelopes and extracts monoisotopic masses of precursor or fragment ions. The performance of spectral deconvolution methods relies heavily on their scoring functions, which distinguish correct envelopes from incorrect ones. A good scoring function increases the accuracy of deconvoluted masses reported from mass spectra. In this paper, we present EnvCNN, a convolutional neural network-based model for evaluating isotopic envelopes. We show that the model outperforms other scoring functions in distinguishing correct envelopes from incorrect ones and that it increases the number of identifications and improves the statistical significance of identifications in top-down spectral interpretation.Titanium dioxide (TiO2) nanomaterials have attracted much interest in life science and biological fields because of their excellent photocatalytic activity and good biocompatibility. However, owing to its wide band gap, photocatalysis of TiO2 can be only triggered by UV light. The limited transparent depth of UV light and the generated reactive oxygen species (ROSs) cause inflammation response of skin tissue, thus posing two major challenges in the photocatalytic application of TiO2-based materials in drug delivery and other biotechnology fields. Here, we propose an upconversion-related strategy to enable the photocatalytic activity of TiO2 nanotubes in near-infrared light and apply the system as a controllable drug delivery platform. More importantly, the ROS-induced cytotoxicity and the preleaching of payloads are significantly reduced on the as-proposed amphiphilic TiO2 nanotubes. The hydrophobic monolayers are served as a "cap" to provide protection for ROS-induced inflammation and long-term storability. This amphiphilic drug delivery system broadens the potential applications of TiO2-based nanomaterials in biomedicine.Parkinson's disease is associated with aggregation of pathological α-synuclein (αSyn) proteins. The central hydrophobic region of αSyn, called NAC, encodes the segment that is crucial and sufficient for the toxic aggregation of αSyn. However, if any other region, including the NAC flanking region, modulates αSyn, aggregation is still unknown. A master-regulator sequence motif is now identified that is critical to controlling the aggregation of the αSyn NAC region. Interestingly, this region was also found to be important for membrane vesicle fusion. read more This master-regulator region could be targeted to prevent αSyn aggregation. The results reveal several unanswered questions about the αSyn aggregation mechanism.Many bacteria use membrane-diffusible small molecule quorum signals to coordinate gene transcription in response to changes in cell density, known as quorum sensing (QS). Among these, acyl-homoserine lactones (AHL) are widely distributed in Proteobacteria and are involved in controlling the expression of virulence genes and biofilm formation in pathogens, such as Pseudomonas aeruginosa. AHL molecules are specifically biosynthesized by the cognate LuxI type AHL synthases using S-adenosylmethionine (SAM) and either acyl carrier protein (ACP)- or CoA-coupled fatty acids through a two-step reaction. Here, we characterize a CoA-dependent LuxI synthase from Rhodopseudomonas palustris that utilizes an aryl-CoA substrate that is environmentally derived, specifically p-coumaric acid. We leverage structures of this aryl-CoA-dependent synthase, along with our prior studies of an acyl-CoA-dependent synthase, to identify residues that confer substrate chain specificity in these enzymes. We test our predictions by carrying out biochemical, kinetic, and structural characterization of representative AHL signal synthases. Our studies provide an understanding of various AHL synthases that may be deployed in synthetic biological applications and inform on the design of specific small molecule therapeutics that can restrict virulence by targeting quorum signaling.Methcathinone (MCAT; 1), the progenitor of numerous and widely abused "synthetic cathinone" central stimulants, exists as a pair of optical isomers. Although S(-)MCAT is several-fold more potent than R(+)MCAT in rodent locomotor stimulation and stimulus generalization studies in rat drug discrimination assays, the individual optical isomers of MCAT have never been directly compared for their actions at monoamine transporters that seem to underlie their actions, and have never been examined for their relative abuse potential. Here, we found that the isomers of MCAT are nearly equieffective at dopamine and norepinephrine transporters (DAT and NET, respectively) as transporter substrates (i.e., as releasing agents), and are >63-fold less potent at the serotonin transporter (SERT). In intracranial self-stimulation (ICSS) studies to evaluate abuse-related drug effects in rats, S(-)MCAT was approximately twice as potent as its R-enantiomer. Achiral analogs, α-methyl MCAT (3) and α-des-methyl MCAT (4), also were DAT/NET substrates and also produced abuse-related ICSS effects, indicating that they retain abuse potential and that they might be useful for the further study of the stereochemistry of synthetic cathinone analogs with chiral β- (or other) substituents.OBJECTIVES High-quality clinical research of resuscitations in a pediatric emergency department is challenging because of the limitations of traditional methods of data collection (chart review, self-report) and the low frequency of cases in a single center. To facilitate valid and reliable research for resuscitations in the pediatric emergency department, investigators from 3 pediatric centers, each with experience completing successful single-center, video-based studies, formed the Videography In Pediatric Emergency Research (VIPER) collaborative. METHODS Our initial effort was the development of a multicenter, video-based registry and simulation-based testing of the feasibility and reliability of the VIPER registry. Feasibility of data collection was assessed by the frequency of an indeterminate response for all data elements in the registry. Reliability was assessed by the calculation of Cohen κ for dichotomous data elements and intraclass correlation coefficients for continuous data elements. RESULTS Video-based data collection was completed for 8 simulated pediatric resuscitations, with at least 2 reviewers per case.