Summary Body composition estimates are widely used in clinical research and field studies as measures of energy‐nutrient balance, functionality and health. Despite their broad relevance and multiple applications, important gaps remain in techniques available for accurately and precisely quantifying body composition in infants and children from birth through 5 years. Identifying these gaps and highlighting research needs in this age group were the topics of a National Institutes of Health workshop...
6m
Abstract Periodontitis is a chronic inflammatory disease of the gums caused by infection with multispecies oral bacteria. Since the periodontopathic bacteria Porphyromonas gingivalis together with Enterococcus faecalis are frequently detected in patients with a severe form of periodontitis, interactions between their virulence factors might play an important role in progression of the disease. P. gingivalis and E. faecalis possess lipopolysaccharide (Pg.LPS) and lipoteichoic acid (Ef.LTA), respectively,...
1h
Data independent acquisition (DIA) is an attractive alternative to standard shotgun proteomics methods for quantitative experiments. However, most DIA methods require collecting exhaustive, sample-specific spectrum libraries with data dependent acquisition (DDA) to detect and quantify peptides. In addition to working with non-human samples, studies of splice junctions, sequence variants, or simply working with small sample yields can make developing DDA-based spectrum libraries impractical. Here...
1h
Molecular mechanisms underlying sperm motility have not been fully explained, particularly in chickens. The objective was to identify seminal plasma proteins associated with chicken sperm motility by comparing the seminal plasma proteomic profile of roosters with low sperm motility (LSM, n = 4) and high sperm motility (HSM, n = 4). Using a label-free MS-based method, a total of 522 seminal plasma proteins were identified, including 386 (~74%) previously reported and 136 novel ones. A total of 70...
1h
Data independent acquisition (DIA) is an attractive alternative to standard shotgun proteomics methods for quantitative experiments. However, most DIA methods require collecting exhaustive, sample-specific spectrum libraries with data dependent acquisition (DDA) to detect and quantify peptides. In addition to working with non-human samples, studies of splice junctions, sequence variants, or simply working with small sample yields can make developing DDA-based spectrum libraries impractical. Here...
9h
Molecular mechanisms underlying sperm motility have not been fully explained, particularly in chickens. The objective was to identify seminal plasma proteins associated with chicken sperm motility by comparing the seminal plasma proteomic profile of roosters with low sperm motility (LSM, n = 4) and high sperm motility (HSM, n = 4). Using a label-free MS-based method, a total of 522 seminal plasma proteins were identified, including 386 (~74%) previously reported and 136 novel ones. A total of 70...
9h
Protein microarrays are crucial tools in the study of proteins in an unbiased, high-throughput manner, as they allow for characterization of up to thousands of individually purified proteins in parallel. The adaptability of this technology has enabled its use in a wide variety of applications, including the study of proteome-wide molecular interactions, analysis of post-translational modifications, identification of novel drug targets, and examination of pathogen-host interactions. In addition, the...
3d
Protein microarrays are crucial tools in the study of proteins in an unbiased, high-throughput manner, as they allow for characterization of up to thousands of individually purified proteins in parallel. The adaptability of this technology has enabled its use in a wide variety of applications, including the study of proteome-wide molecular interactions, analysis of post-translational modifications, identification of novel drug targets, and examination of pathogen-host interactions. In addition, the...
3d
The degradation of intra- and extracellular proteins is essential in all cell types and mediated by two systems, the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway. This study investigates the changes in autophagosomal and lysosomal proteomes upon inhibition of proteasomes by bortezomib (BTZ) or MG132. We find an increased abundance of more than 50 proteins in lysosomes of cells in which the proteasome is inhibited. Among those are dihydrofolate reductase (DHFR), ß-Catenin and...
4d
The degradation of intra- and extracellular proteins is essential in all cell types and mediated by two systems, the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway. This study investigates the changes in autophagosomal and lysosomal proteomes upon inhibition of proteasomes by bortezomib (BTZ) or MG132. We find an increased abundance of more than 50 proteins in lysosomes of cells in which the proteasome is inhibited. Among those are dihydrofolate reductase (DHFR), ß-Catenin and...
4d
Telemedicine and e-Health, Ahead of Print.
1h
Telemedicine and e-Health, Ahead of Print.
3d
Telemedicine and e-Health, Ahead of Print.
3d
Telemedicine and e-Health, Ahead of Print.
3d
Telemedicine and e-Health, Ahead of Print.
4d
Telemedicine and e-Health, Ahead of Print.
4d
Lytic replication of Epstein–Barr virus (EBV) is not only essential for its cell-to-cell spread and host-to-host transmission, but also contributes to EBV-induced oncogenesis. Thus, blocking EBV lytic replication could be a strategy for managing EBV-associated diseases. Previously we identified a series of natural lignans isolated from the roots of Saururus chinensis (Asian lizard’s tail) that efficiently blocks EBV lytic replication and virion production with low cytotoxicity. In the current study,...
1h
Cohesin is a DNA-associated protein complex that forms a tripartite ring controlling sister chromatid cohesion, chromosome segregation and organization, DNA replication, and gene expression. Sister chromatid cohesion is established by the protein acetyltransferase Eco1, which acetylates two conserved lysine residues on the cohesin subunit Smc3 and thereby ensures correct chromatid separation in yeast (Saccharomyces cerevisiae) and other eukaryotes. However, the consequence of Eco1-catalyzed cohesin...
1h
Autophagy and lysosomal activities play a key role in the cell by initiating and carrying out the degradation of misfolded proteins. Transcription factor EB (TFEB) functions as a master controller of lysosomal biogenesis and function during lysosomal stress, controlling most, but, importantly, not all lysosomal genes. Here, we sought to better understand the regulation of lysosomal genes whose expression does not appear to be controlled by TFEB. Sixteen of these genes were screened for transactivation...
1h
Abstract Purpose The aim of this study was to determine the accuracy of orthopantomograms (OPGs) when assessing post-operative temporomandibular joint (TMJ) implant position, compared with cone beam computerized tomography (CBCT). Methods A retrospective analysis was undertaken on six adult patients who were implanted with a custom TMJ prosthesis due to end-stage...
2d
Excessive generation of oxidants by immune cells results in acute tissue damage. One mechanism by which oxidant exposure could have long-term impact is through modulation of epigenetic pathways. We hypothesized that methylation of newly synthesized DNA in proliferating cells can be altered by oxidants that target DNA methyltransferase (DNMT) activity or deplete its substrate, the methyl donor SAM. To this end, we investigated the impact of two oxidants produced by neutrophils, hydrogen peroxide (H2O2)...
1h
One long-standing knowledge gap is the role of nuclear proteins in mRNA translation. Nuclear RNA helicase A (DHX9/RHA) is necessary for the translation of the mRNAs of JunD proto-oncogene AP-1 transcription factor subunit (JUND) and HIV-1 genes, and nuclear cap–binding protein 1 (NCBP1)/CBP80 is a component of HIV-1 polysomes. The protein kinase mTOR activates canonical messenger ribonucleoproteins (mRNPs) by post-translationally downregulating the eIF4E inhibitory protein, 4E-BP1. We posited here...
1h
The mammalian target of rapamycin complex 1 (mTORC1) senses nutrients to mediate anabolic processes within the cell. Exactly how mTORC1 promotes cell growth remains unclear. Here, we identified a novel mTORC1-interacting protein called A-kinase anchoring protein 8L (AKAP8L). Using biochemical assays, we found that the N-terminal region of AKAP8L binds to mTORC1 in the cytoplasm. Importantly, loss of AKAP8L decreased mTORC1-mediated processes such as translation, cell growth and cell proliferation....
1h
Members of the EAP family of Staphylococcus aureus immune evasion proteins potently inhibit the neutrophil serine proteases (NSPs) neutrophil elastase, cathepsin-G, and proteinase-3. Previously, we determined a 1.8 Å resolution crystal structure of the EAP family member EapH1 bound to neutrophil elastase. This structure revealed that EapH1 blocks access to the enzyme’s active site by forming a non-covalent complex with this host protease. To determine how EapH1 inhibits other NSPs, we studied here...
3d
2-Oxoadipate dehydrogenase (E1a, also known as DHTKD1, dehydrogenase E1 and transketolase domain-containing protein 1) is a thiamin diphosphate-dependent enzyme and part of the 2-oxoadipate dehydrogenase complex (OADHc) in L-lysine catabolism. Genetic findings have linked mutations in the DHTKD1 gene to several metabolic disorders. These include alpha-aminoadipic and alpha-ketoadipic aciduria (AMOXAD), a rare disorder of L-lysine, L-hydroxylysine, and L-tryptophan catabolism, characterized by clinical...
3d
The cytochrome P450 monooxygenase P450 BM3 (BM3) is a biotechnologically important and versatile enzyme capable of producing important compounds such as the medical drugs pravastatin and artemether, and the steroid hormone testosterone. BM3 is a natural fusion enzyme comprising two major domains: a cytochrome P450 (heme-binding) catalytic domain and a NADPH-cytochrome P450 reductase (CPR) domain containing FAD and FMN cofactors in distinct domains of the CPR. A crystal structure of full-length BM3...
3d
G protein–coupled receptors (GPCRs) use a series of conserved microswitches to transmit signals across the cell membrane via an allosteric network encompassing the ligand-binding site and the G protein–binding site. Crystal structures of GPCRs provide snapshots of their inactive and active states, but poorly describe the conformational dynamics of the allosteric network that underlies GPCR activation. Here, we analyzed the correlation between ligand binding and receptor conformation of the α1A-adrenoceptor,...
3d
The circadian clock in plants temporally coordinates biological processes throughout the day, synchronizing gene expression with diurnal environmental changes. Circadian oscillator proteins are known to regulate the expression of clock-controlled plant genes by controlling their transcription. Here, using a high-throughput RNA-seq approach, we examined the genome-wide circadian and diurnal control of the Arabidopsis transcriptome, finding that the oscillation patterns of different transcripts of...
3d
Cleavage of influenza virus hemagglutinin (HA) by host proteases is essential for virus infectivity. HA of most influenza A and B (IAV/IBV) viruses is cleaved at a monobasic motif by trypsin-like proteases. Previous studies have reported that transmembrane serine protease 2 (TMPRSS2) is essential for activation of H7N9 and H1N1pdm IAV in mice, but that H3N2 IAV and IBV activation is independent of TMPRSS2 and carried out by as-yet-undetermined protease(s). Here, to identify additional H3 IAV- and...
3d
The intracellular bacterial pathogen Coxiella burnetii is the etiological agent of the emerging zoonosis Q fever. Crucial to its pathogenesis is type 4b secretion system (T4SS)-mediated secretion of bacterial effectors into host cells that subvert host cell membrane trafficking, leading to the biogenesis of a parasitophorous vacuole for intracellular replication. The characterization of prokaryotic Serine/Threonine Protein Kinases (STPKs) in bacterial pathogens is emerging as an important strategy...
3d
The bacterial protein WhiD belongs to the Wbl family of iron–sulfur [Fe-S] proteins present only in the actinomycetes. In Streptomyces coelicolor, it is required for the late stages of sporulation, but precisely how it functions is unknown. Here, we report results from in vitro and in vivo experiments with WhiD from Streptomyces venezuelae (SvWhiD), which differs from S. coelicolor WhiD (ScWhiD) only at the C terminus. We observed that, like ScWhiD and other Wbl proteins, SvWhiD binds a [4Fe-4S]...
3d
SHC adaptor protein (SHCA) and lipoma-preferred partner (LPP) mediate transforming growth factor β (TGFβ)-induced breast cancer cell migration and invasion. Reduced expression of either protein diminishes breast cancer lung metastasis, but the reason for this effect is unclear. Here, using total internal reflection fluorescence (TIRF) microscopy, we found that TGFβ enhances the assembly and disassembly rates of paxillin-containing adhesions in an SHCA-dependent manner through the phosphorylation...
4d
The E2 glycoprotein of hepatitis C virus (HCV) is the major target of broadly neutralizing antibodies (bNAbs) that are critical for the efficacy of a prophylactic HCV vaccine. We previously showed that a cell culture-derived, disulfide-linked high-molecular-weight (HMW) form of the E2 receptor-binding domain lacking three variable regions, D123-HMW, elicits broad neutralizing activity against the 8 genotypes of HCV. A limitation to the use of this antigen is that it is produced only at low yields...
4d
Platinum-based chemotherapies, including oxaliplatin, are a mainstay in the management of solid tumors and induce cell death by forming intrastrand dinucleotide DNA adducts. Despite their common use, they are highly toxic, and approximately half of cancer patients have tumors that are either intrinsically resistant or develop resistance. Previous studies suggest that this resistance is mediated by variations in DNA repair levels or net drug influx. Here, we aimed to better define the roles of nucleotide...
4d
Severe congenital neutropenia (SCN) is characterized by the near absence of neutrophils, rendering individuals with this disorder vulnerable to recurrent, life-threatening infections. A majority of SCN cases arises because germline mutations in the gene elastase, neutrophil expressed (ELANE), encoding the neutrophil granule serine protease, neutrophil elastase. Treatment with a high dose of granulocyte colony-stimulating factor (GCSF) increases neutrophil production and reduces infection risk. How...
4d
NAD+ is an essential metabolite participating in cellular biochemical processes and signaling. The regulation and interconnection among multiple NAD+ biosynthesis pathways are incompletely understood. Yeast (Saccharomyces cerevisiae) cells lacking the N-terminal (Nt) protein acetyltransferase complex NatB exhibit an approximate 50% reduction in NAD+ levels and aberrant metabolism of NAD+ precursors, changes that are associated with a decrease in nicotinamide mononucleotide adenylyltransferase (Nmnat)...
4d
CTX-M β-lactamases are widespread in Gram-negative bacterial pathogens and provide resistance to the cephalosporin cefotaxime, but not to the related antibiotic, ceftazidime. Nevertheless, variants have emerged that confer resistance to ceftazidime. Two natural mutations, causing P167S and D240G substitutions in the CTX-M enzyme, result in 10-fold increased hydrolysis of ceftazidime. Although the combination of these mutations would be predicted to increase ceftazidime hydrolysis further, the P167S/D240G...
4d
Epidermal growth factor receptor (EGFR) signalling is a highly regulated process with a tight balance between receptor activation and inactivation in invasive breast carcinomas (IBCs) particularly in triple-negative carcinomas (TNC). Clinical trials using anti-EGFR therapies are actually performed although no activating alterations (mutations, amplifications, or rearrangements) of EGFR have been clearly recognized in order to identify new targeted modalities for IBCs. We explored mammary-derived...
2h
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