Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes.

Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of γ-glutamylcysteine synthetase (γ-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine in vivo. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH

Molecular Analysis of Two Different MRSA Clones ST188 and ST3268 From Primates (Macaca spp.) in a United States Primate Center

Methicillin-resistant Staphylococcus aureus (MRSA) were identified in macaques, their environmental facility, and nasal cultures of personnel from the Washington National Primate Research Center [WaNPRC] and included MRSA ST188 SCCmec IV and MRSA ST3268 SCCmec V. The aim of the current study was to determine the carriage of virulence genes, antibiotic resistance genes, and other characteristics of the primate MRSA isolates to determine if there were any obvious differences that would account for differences in transmission within the WaNPRC facility. In total, 1,199 samples from primates were tested for the presence of MRSA resulting in 158 MRSA-positive samples. Fifteen ST188 isolates (all from Macaca nemestrina) and nine ST3268 (four from Macaca mulatta, two from Macaca fascicularis, three from M. nemestrina), were selected for further characterization. All but one of the 15 ST188 isolates had spa type t189 and the remaining one had spa type t3887. These isolates were resistant to β-lactams [blaZ, mecA], macrolides/lincosamides [erm(B)], aminoglycosides [aacA-aphD], and fluoroquinolones. Five isolates were additionally resistant to tetracyclines [tet(K)] and had elevated MICs for benzalkonium chloride [qacC]. In comparison, the nine ST3268 isolates had the related spa types t15469 (n = 5) and t13638 (n = 4). All nine ST3268 isolates were resistant to β-lactams [blaZ, mecA], and tetracyclines [tet(K)]. Some isolates were additionally resistant to aminoglycosides [aacA-aphD], fluoroquinolones and/or showed elevated MICs for benzalkonium chloride [qacC]. In contrast to the ST188 isolates, the ST3268 isolates had the enterotoxin gene cluster egc [seg, sei, selm, seln, selo, selu] and enterotoxin genes sec and sel. The two clones have differences regarding their spa types, virulence and antibiotic resistance genes as well as ST and SCCmec types. However, the data presented does not provide insight into why ST188 spreads easily while ST3268 did not spread within the WaNPRC in-house primates.Methicillin-resistant Staphylococcus aureus (MRSA) were identified in macaques, their environmental facility, and nasal cultures of personnel from the Washington National Primate Research Center [WaNPRC] and included MRSA ST188 SCCmec IV and MRSA ST3268 SCCmec V. The aim of the current study was to determine the carriage of virulence genes, antibiotic resistance genes, and other characteristics of the primate MRSA isolates to determine if there were any obvious differences that would account for differences in transmission within the WaNPRC facility. In total, 1,199 samples from primates were tested for the presence of MRSA resulting in 158 MRSA-positive samples. Fifteen ST188 isolates (all from Macaca nemestrina) and nine ST3268 (four from Macaca mulatta, two from Macaca fascicularis, three from M. nemestrina), were selected for further characterization. All but one of the 15 ST188 isolates had spa type t189 and the remaining one had spa type t3887. These isolates were resistant to β-lactams [blaZ, mecA], macrolides/lincosamides [erm(B)], aminoglycosides [aacA-aphD], and fluoroquinolones. Five isolates were additionally resistant to tetracyclines [tet(K)] and had elevated MICs for benzalkonium chloride [qacC]. In comparison, the nine ST3268 isolates had the related spa types t15469 (n = 5) and t13638 (n = 4). All nine ST3268 isolates were resistant to β-lactams [blaZ, mecA], and tetracyclines [tet(K)]. Some isolates were additionally resistant to aminoglycosides [aacA-aphD], fluoroquinolones and/or showed elevated MICs for benzalkonium chloride [qacC]. In contrast to the ST188 isolates, the ST3268 isolates had the enterotoxin gene cluster egc [seg, sei, selm, seln, selo, selu] and enterotoxin genes sec and sel. The two clones have differences regarding their spa types, virulence and antibiotic resistance genes as well as ST and SCCmec types. However, the data presented does not provide insight into why ST188 spreads easily while ST3268 did not spread within the WaNPRC in-house primates

The Effect of Maja Fruit [Aegle Marmelos (L) Correa] on Inflammation Markers Involved in the Aging Process

Background: Aging is a process that every living creature will pass through and involves various factors. Increased inflammatory factors can be caused by hypoxia which forms Reactive Oxygen Species (ROS) and damages macromolecules and causes the acceleration of the aging process. Maja plants, empirically have long been used as medicinal plants, research on Maja leaves shows anti-inflammatory and antioxidant potential.Objective: The purpose of this study was to find out and understand the potential of Maja fruit in the presence of inflammatory markers of IL-6 and TNF-α which are involved in the aging process.Methods: This research was in vivo experimental, using male experimental animals Sprague Dawley rats divided into 8 groups (n = 4), and divided into 2 groups (fed with Maja ethanol extract (400 mg/ kg/day, 14 days) and not force-fed). Each group was divided into 4 subgroups (normoxia, hypoxia (O2 8%, N2 92%) for 3, 7 and 14 days). At the end of the trial period, animal blood was examined for IL-6 and TNF-α concentrations using the ELISA method.Results: The results showed an increase in levels of IL-6 and TNF-α both in the group fed and not fed in line with the duration of hypoxia when compared with controls. However, groups that are not force-fed show a higher pattern compared to those who are force-fed.Conclusion : The ethanol extract of Maja fruit can help slow down the aging process

The Diboson Excess: Experimental Situation and Classification of Explanations; A Les Houches Pre-Proceeding

We examine the `diboson' excess at $\sim 2$ TeV seen by the LHC experiments in various channels. We provide a comparison of the excess significances as a function of the mass of the tentative resonance and give the signal cross sections needed to explain the excesses. We also present a survey of available theoretical explanations of the resonance, classified in three main approaches. Beyond that, we discuss methods to verify the anomaly, determining the major properties of the various surpluses and exploring how different models can be discriminated. Finally, we give a tabular summary of the numerous explanations, presenting their main phenomenological features.Comment: 37 pages, 9 Figures, 1 Tabl

Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'

We combined large-scale mRNA expression analysis and gene mapping to identify genes and loci that control hematopoietic stem cell (HSC) function. We measured mRNA expression levels in purified HSCs isolated from a panel of densely genotyped recombinant inbred mouse strains. We mapped quantitative trait loci (QTLs) associated with variation in expression of thousands of transcripts. By comparing the physical transcript position with the location of the controlling QTL, we identified polymorphic cis-acting stem cell genes. We also identified multiple trans-acting control loci that modify expression of large numbers of genes. These groups of coregulated transcripts identify pathways that specify variation in stem cells. We illustrate this concept with the identification of candidate genes involved with HSC turnover. We compared expression QTLs in HSCs and brain from the same mice and identified both shared and tissue-specific QTLs. Our data are accessible through WebQTL, a web-based interface that allows custom genetic linkage analysis and identification of coregulated transcripts.

Conserved YKL-40 changes in mice and humans after postoperative delirium

Delirium is a common postoperative neurologic complication among older adults. Despite its prevalence (14%–50%) and likely association with inflammation, the exact mechanisms that underpin postoperative delirium are unclear. This project aimed to characterize systemic and central nervous system (CNS) inflammatory changes following surgery in mice and humans. Matched plasma and cerebrospinal fluid (CSF) samples from the “Investigating Neuroinflammation Underlying Postoperative Brain Connectivity Changes, Postoperative Cognitive Dysfunction, Delirium in Older Adults” (INTUIT; NCT03273335) study were compared to murine endpoints. Delirium-like behavior was evaluated in aged mice using the 5-Choice Serial Reaction Time Test (5-CSRTT). Using a well established orthopedic surgical model in the FosTRAP reporter mouse we detected neuronal changes in the prefrontal cortex, an area implicated in attention, but notably not in the hippocampus. In aged mice, plasma interleukin-6 (IL-6), chitinase-3-like protein 1 (YKL-40), and neurofilament light chain (NfL) levels increased after orthopedic surgery, but hippocampal YKL-40 expression was decreased. Given the growing evidence for a YKL-40 role in delirium and other neurodegenerative conditions, we assayed human plasma and CSF samples. Plasma YKL-40 levels were similarly increased after surgery, with a trend toward a greater postoperative plasma YKL-40 increase in patients with delirium. However, YKL-40 levels in CSF decreased following surgery, which paralleled the findings in the mouse brain. Finally, we confirmed changes in the blood-brain barrier (BBB) as early as 9 h after surgery in mice, which warrants more detailed and acute evaluations of BBB integrity following surgery in humans. Together, these results provide a nuanced understanding of neuroimmune interactions underlying postoperative delirium in mice and humans, and highlight translational biomarkers to test potential cellular targets and mechanisms

Detecting gravitational waves from cosmological phase transitions with LISA: an update

We investigate the potential for observing gravitational waves from cosmological phase transitions with LISA in light of recent theoretical and experimental developments. Our analysis is based on current state-of-the-art simulations of sound waves in the cosmic fluid after the phase transition completes. We discuss the various sources of gravitational radiation, the underlying parameters describing the phase transition and a variety of viable particle physics models in this context, clarifying common misconceptions that appear in the literature and identifying open questions requiring future study. We also present a web-based tool, PTPlot, that allows users to obtain up-to-date detection prospects for a given set of phase transition parameters at LISA.acceptedVersio