Two Genes on A/J Chromosome 18 Are Associated with Susceptibility to Staphylococcus aureus Infection by Combined Microarray and QTL Analyses

Although it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared to C57BL/6J, the specific genes responsible for this differential phenotype are unknown. Using chromosome substitution strains (CSS), we found that loci on chromosomes 8, 11, and 18 influence susceptibility to S. aureus sepsis in A/J mice. We then used two candidate gene selection strategies to identify genes on these three chromosomes associated with S. aureus susceptibility, and targeted genes identified by both gene selection strategies. First, we used whole genome transcription profiling to identify 191 (56 on chr. 8, 100 on chr. 11, and 35 on chr. 18) genes on our three chromosomes of interest that are differentially expressed between S. aureus-infected A/J and C57BL/6J. Second, we identified two significant quantitative trait loci (QTL) for survival post-infection on chr. 18 using N2 backcross mice (F1 [C18A]×C57BL/6J). Ten genes on chr. 18 (March3, Cep120, Chmp1b, Dcp2, Dtwd2, Isoc1, Lman1, Spire1, Tnfaip8, and Seh1l) mapped to the two significant QTL regions and were also identified by the expression array selection strategy. Using real-time PCR, 6 of these 10 genes (Chmp1b, Dtwd2, Isoc1, Lman1, Tnfaip8, and Seh1l) showed significantly different expression levels between S. aureus-infected A/J and C57BL/6J. For two (Tnfaip8 and Seh1l) of these 6 genes, siRNA-mediated knockdown of gene expression in S. aureus–challenged RAW264.7 macrophages induced significant changes in the cytokine response (IL-1 β and GM-CSF) compared to negative controls. These cytokine response changes were consistent with those seen in S. aureus-challenged peritoneal macrophages from CSS 18 mice (which contain A/J chromosome 18 but are otherwise C57BL/6J), but not C57BL/6J mice. These findings suggest that two genes, Tnfaip8 and Seh1l, may contribute to susceptibility to S. aureus in A/J mice, and represent promising candidates for human genetic susceptibility studies

Deep Neural Network Model for Automated Detection of Alzheimer’s Disease using EEG Signals

Our brain is our body’s control centre and is essential for proper functioning of the body. Alzheimer’s disease is a chronic neurodegenerative disease that affects the cerebral cortex of the brain and causes memory loss and loss of cognitive thinking. EEG (Electroencephalography) is a method of recording neurological electrical activity with electrodes. It was chosen as it is a simple, painless procedure. This paper suggests an automated and accurate algorithm for the detection of Alzheimer's Disease using EEG signals with a combination of Signal processing and Deep Learning Methods. Concepts like Butterworth filters, DWT, statistical parameters, Data Augmentation and CNN were used in order to achieve a classification algorithm with high accuracy. A total highest  system  accuracy of 97.61% was achieved

A Review on Oral Strip Technology: A Feasible Technique to Improve Patient Compliance by Oral Route

Oral Strip Technology (OST) is one of the Oral drug delivery systemwhichever the currentyears gaining much attention and this technology is attracting many of the research groups toconcentrate their research onit. Dysphasia is common problem seen in pediatrics and geriatric patient’s population due to administration of monolithic solid dosage forms which are also seen in the case of fast dissolving tablets considering the size of the tablets and this problem is eliminated with introduction of OST. OST is mainly used for buccoadhesive systems in which they are retained in the oral cavity to release drug in controlled manner. This technology has also been used for local action and rapid release products.Strips are ease of handling and administration, transportability, high stability, no special packaging material and/or processing requirements, no requirement of water for application. The advantage of OST over Orally Disintegrating Tablets is that the OST is relatively easy to fabricate whereas ODTs requires complicated and expensive process used to manufacture thus increasing the overall cost of the therapy. This review article enlightens the present and future perspective of OST along with its materials used for formulation, method of preparation, evaluation and benefits.

Critical Role of NOD2 in Regulating the Immune Response to Staphylococcus aureus▿

NOD2 (the nucleotide-binding oligomerization domain containing protein 2) is known to be involved in host recognition of bacteria, although its role in the host response to Staphylococcus aureus infection is unknown. NOD2-deficient (Nod2−/−) mice and wild-type (WT) littermate controls were injected intraperitoneally with S. aureus suspension (107 bacteria/g of body weight), and their survival was monitored. Cultured bone marrow-derived neutrophils were harvested from Nod2−/− and WT mice and tested for cytokine production and phagocytosis. Compared to WT mice, Nod2−/− mice were significantly more susceptible to S. aureus infection (median survival of 1.5 days versus >5 days; P = 0.003) and had a significantly higher bacterial tissue burden. Cultured bone marrow-derived neutrophils from Nod2−/− and WT mice had similar levels of peritoneal neutrophil recruitment and intracellular killing, but bone marrow-derived neutrophils from Nod2−/− mice had significantly reduced ability to internalize fluorescein-labeled S. aureus. Nod2−/− mice had significantly higher levels of Th1-derived cytokines in serum (tumor necrosis factor alpha, gamma interferon, and interleukin-2 [IL-2]) compared to WT mice, whereas the levels of Th2-derived cytokines (IL-1β, IL-4, IL-6, and IL-10) were similar in Nod2−/− and WT mice. Thus, mice deficient in NOD2 are more susceptible to S. aureus. Increased susceptibility is due in part to defective neutrophil phagocytosis, elevated serum levels of Th1 cytokines, and a higher bacterial tissue burden

Acrolein-Activated Matrix Metalloproteinase 9 Contributes to Persistent Mucin Production

Chronic obstructive pulmonary disease (COPD), a global public health problem, is characterized by progressive difficulty in breathing, with increased mucin production, especially in the small airways. Acrolein, a constituent of cigarette smoke and an endogenous mediator of oxidative stress, increases airway mucin 5, subtypes A and C (MUC5AC) production; however, the mechanism remains unclear. In this study, increased mMUC5AC transcripts and protein were associated with increased lung matrix metalloproteinase 9 (mMMP9) transcripts, protein, and activity in acrolein-exposed mice. Increased mMUC5AC transcripts and mucin protein were diminished in gene-targeted Mmp9 mice [Mmp9(-/-)] or in mice treated with an epidermal growth factor receptor (EGFR) inhibitor, erlotinib. Acrolein also decreased mTissue inhibitor of metalloproteinase protein 3 (an MMP9 inhibitor) transcript levels. In a cell-free system, acrolein increased pro-hMMP9 cleavage and activity in concentrations (100–300 nM) found in sputum from subjects with COPD. Acrolein increased hMMP9 transcripts in human airway cells, which was inhibited by an MMP inhibitor, EGFR-neutralizing antibody, or a mitogen-activated protein kinase (MAPK) 3/2 inhibitor. Together these findings indicate that acrolein can initiate cleavage of pro-hMMP9 and EGFR/MAPK signaling that leads to additional MMP9 formation. Augmentation of hMMP9 activity, in turn, could contribute to persistent excessive mucin production

Center Variation in Intestinal Microbiota Prior to Late-Onset Sepsis in Preterm Infants

<div><p>Objective</p><p>Late onset sepsis (LOS) contributes to mortality and morbidity in preterm infants. We tested the hypotheses that microbes causing LOS originate from the gut, and that distortions in the gut microbial community increases subsequent risk of LOS.</p><p>Study Design</p><p>We examined the gut microbial community in prospectively collected stool samples from preterm infants with LOS and an equal number of age-matched controls at two sites (Cincinnati, OH and Birmingham, AL), by sequencing the bacterial 16S rDNA. We confirmed our findings in a subset of infants by whole genome shotgun sequencing, and analyzed the data using R and LEfSe.</p><p>Results</p><p>Infants with LOS in Cincinnati, as compared to controls, had less abundant <i>Actinobacteria</i> in the first samples after birth (median 18 days before sepsis onset), and less abundant <i>Pseudomonadales</i> in the last samples collected prior to LOS (median 8 days before sepsis onset). Infants with LOS in Birmingham, as compared to controls, had no differences identified in the first sample microbial communities, but <i>Lactobacillales</i> was less abundant in the last samples prior to LOS (median 4 days before sepsis onset). Sequencing identified detectable levels of the sepsis-causative organism in stool samples prior to disease onset for 82% of LOS cases.</p><p>Conclusions</p><p>Translocation of gut microbes may account for the majority of LOS cases. Distortions in the fecal microbiota occur prior to LOS, but the form of distortion depends on timing and site. The microbial composition of fecal samples does not predict LOS onset in a generalizable fashion.</p></div

First sample classification tree results.

<p>(A) Birmingham results, showing infants colonized with <i>Streptococcaceae</i> and infants with higher levels of <i>Clostridia</i> are at greater risk of sepsis. (B) Cincinnati results, showing that infants colonized with greater relative abundance of <i>Actinobacteria</i> and infants with lower relative abundance of <i>Bacilli</i> are protected from sepsis.</p