Nonalcoholic Steatohepatitis: Role of Gut Microbiota is Dependent on Lipopolysaccharide-Toll-like Receptor-4 Axis

Hepatic steatosis is the hepatic manifestation of metabolic syndrome which is increasingly becoming a health problem worldwide, especially in the western hemisphere. Hepatic steatosis is benign, but long standing hepatic steatosis can lead to non-alcoholic steatohepatitis (NASH). NASH is a form of nonalcoholic fatty liver disease where excessive fat accumulation in the liver leads to chronic inflammation of a patient without any history of alcohol abuse. However, the mechanism underlying the progression of hepatic steatosis to NASH is unclear. Role of gut microbiota in metabolic syndrome has long been reported. Here, we hypothesized that gut microbiota plays an important role in the modulation of NASH through the involvement of lipopolysaccharide (LPS)-toll-like receptor-4 (TLR-4) pathway in dietary fat mediated hepatic steatosis. To test this hypothesis, germ free or broad-spectrum antibiotics-treated mice were fed high fat diet, which resulted in decreased level of inflammation in their fatty liver compared to the specific pathogen free control mice. This result demonstrated the involvement of gut microbiota in mediating NASH. To address the role of LPS-TLR-4 pathway, broad spectrum antibiotics-treated mice fed high fat diet were injected i.p. with low dose LPS, resulting in an increased level of inflammation in the liver which was decreased upon the co-treatment with TAK-242, an inhibitor of TLR-4. To investigate the role of TLR-4- expressing kupffer cells in mediating NASH, wild-type kupffer cells in the liver of wild-type mice were replaced with TLR-4 KO kupffer cells by bone marrow transplantation, which resulted in a decreased level of inflammation in liver upon NASH induction. It was also investigated whether the peroxisomal anti-oxidative function is altered in the livers of mice fed high fat diet in a TLR-4 dependent manner. Indeed, the level and function of catalase, the principal antioxidative enzyme in peroxisomes, was decreased in mice fed high fat diet, which was reversed in TLR-4 KO mice fed high fat diet. This individual piece of data demonstrated the role of TLR-4 pathway in modulating NASH through the alteration of peroxisomal anti-oxidative function. In conclusion, this project established the role of gut microbiota in modulating NASH which is dependent on LPS-TLR-4 pathway

Balancing for an effective communication in organizations

Communication is an essential part of all activities of organizations. However, it is affected by technology. Today, email and social media are popular methods of communication in organizations. Each of the listed methods has advantages and disadvantages which will be discussed in this letter which tries to drive the attention of organizations to the need for a standard and balanced approach toward communication

Cytokine-Neuroantigen Fusion Proteins as a New Class of Tolerogenic, Therapeutic Vaccines for Treatment of Inflammatory Demyelinating Disease in Rodent Models of Multiple Sclerosis

Myelin-specific induction of tolerance represents a promising means to modify the course of autoimmune inflammatory demyelinating diseases such as multiple sclerosis (MS). Our laboratory has focused on a novel preclinical strategy for the induction of tolerance to the major encephalitogenic epitopes of myelin that cause experimental autoimmune encephalomyelitis (EAE) in rats and mice. This novel approach is based on the use of cytokine-NAg (neuroantigen) fusion proteins comprised of the native cytokine fused either with or without a linker to a NAg domain. Several single-chain cytokine-NAg fusion proteins were tested including GMCSF-NAg, IFNbeta-NAg, NAgIL16, and IL2-NAg. These cytokine-NAg vaccines were tolerogenic, therapeutic vaccines that had tolerogenic activity when given as pre-treatments before encephalitogenic immunization and also were effective as therapeutic interventions during the effector phase of EAE. The rank order of inhibitory activity was as follows: GMCSF-NAg, IFNbeta-NAg > NAgIL16 > IL2-NAg > MCSF-NAg, IL4-NAg, IL-13-NAg, IL1RA-NAg, and NAg. Several cytokine-NAg fusion proteins exhibited antigen-targeting activity. High affinity binding of the cytokine domain to specific cytokine receptors on particular subsets of APC resulted in the concentrated uptake of the NAg domain by those APC which in turn facilitated the enhanced processing and presentation of the NAg domain on cell surface MHC class II glycoproteins. For most cytokine-NAg vaccines, the covalent linkage of the cytokine domain and NAg domain was required for inhibition of EAE, thereby indicating that antigenic targeting of the NAg domain to APC was also required in vivo for tolerogenic activity. Overall, these studies introduced a new concept of cytokine-NAg fusion proteins as a means to induce tolerance and to inhibit the effector phase of autoimmune disease. The approach has broad application for suppressive vaccination as a therapy for autoimmune diseases such as MS

What lean is really about: Malaysian automotive perspective

With the tremendous advancement of lean, it has evolved a lot. Many authors have tried to express true nature of lean invarious ways. But still it remains incomplete and ambiguous that it is possible to create a versatile but easily understandable and acceptably meaningful definition. Specially, lean is recommended to be practiced and followed by adapting it to the currentoperational and cultural status and future requirements of the specific industry. So,the author has interviewed 16 lean experts from different key functional areas in a renowned Malaysian automotive industry, and based on the analysis of qualitative dataand information received from them, proposed a new definition of lean. With clear fundamental understanding, the journey of lean is expected to be more effective, efficient and sustainable to maximize productivity and quality with lower cost and time spent in any organization

Predicting risks of low birth weight in Bangladesh with machine learning.

Background and objectiveLow birth weight is one of the primary causes of child mortality and several diseases of future life in developing countries, especially in Southern Asia. The main objective of this study is to determine the risk factors of low birth weight and predict low birth weight babies based on machine learning algorithms.Materials and methodsLow birth weight data has been taken from the Bangladesh Demographic and Health Survey, 2017-18, which had 2351 respondents. The risk factors associated with low birth weight were investigated using binary logistic regression. Two machine learning-based classifiers (logistic regression and decision tree) were adopted to characterize and predict low birth weight. The model performances were evaluated by accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve.ResultsThe average percentage of low birth weight in Bangladesh was 16.2%. The respondent's region, education, wealth index, height, twin child, and alive child were statistically significant risk factors for low birth weight babies. The logistic regression-based classifier performed 87.6% accuracy and 0.59 area under the curve for holdout (90:10) cross-validation, whereas the decision tree performed 85.4% accuracy and 0.55 area under the curve.ConclusionsLogistic regression-based classifier provided the most accurate classification of low birth weight babies and has the highest accuracy. This study's findings indicate the necessity for an efficient, cost-effective, and integrated complementary approach to reduce and correctly predict low birth weight babies in Bangladesh

Standardizing the Concept of Lean: A Literature Review

In modern day‟s global competition, companies adopting lean management to maximize productivity and quality with lower cost and time spent. But the success rate of lean implementation is far below than assumed. The authors noticed that there is a scope to research onunderstanding lean by definitions. Fundamentally, the term “Lean”, mostly representing the Toyota production system has been being defined by many authors in many forms. But still the uniformity and clarity is not gained to come to a conclusion with consensus. Hence thispaper aims to eliminate variability in defining lean bycreatinga versatile, easily understandable and acceptable meaningby reviewing contemporary literature and interviewing industry experts

Anomalous Hall effect of metallic Be/Si pair δ-doped GaAs structures

Metallic samples of Be and Si pair δ-doped GaAs structures which undergo a metal-insulator transition with a decrease in the hole concentration are investigated by Hall resistance and magnetoresistance measurements. The anomalous Hall effect and negative magnetoresistance are observed from the samples in a temperature range above 70 K. Magnitudes of negative magnetoresistance and anomalous Hall resistance significantly vary among the samples, although their doping conditions are close to one another. Dependence of anomalous Hall resistance on the temperature and applied magnetic field is closely correlated to that of negative magnetoresistance for each sample. Their dependence is explained on the basis of a paramagnetic state of localized magnetic moments coexisting with itinerant holes in these samples. Both anomalous Hall effect and negative magnetoresistance decrease with lowering the temperature from 150 K and vanish at a temperature around 70 K, a possible origin of which is discussed

Spatiotemporal nexus between vegetation change and extreme climatic indices and their possible causes of change

Climate extremes have a significant impact on vegetation. However, little is known about vegetation response to climatic extremes in Bangladesh. The association of Normalized Difference Vegetation Index (NDVI) with nine extreme precipitation and temperature indices was evaluated to identify the nexus between vegetation and climatic extremes and their associations in Bangladesh for the period 1986–2017. Moreover, detrended fluctuation analysis (DFA) and Morlet wavelet analysis (MWA) were employed to evaluate the possible future trends and decipher the existing periodic cycles, respectively in the time series of NDVI and climate extremes. Besides, atmospheric variables of ECMWF ERA5 were used to examine the casual circulation mechanism responsible for climatic extremes of Bangladesh. The results revealed that the monthly NDVI is positively associated with extreme rainfall with spatiotemporal heterogeneity. Warm temperature indices showed a significant negative association with NDVI on the seasonal scale, while precipitation and cold temperature extremes showed a positive association with yearly NDVI. The DEA revealed a continuous increase in temperature extreme in the future, while no change in precipitation extremes. NDVI also revealed a significant association with extreme temperature indices with a time lag of one month and with precipitation extreme without time lag. Spatial analysis indicated insensitivity of marshy vegetation type to climate extremes in winter. The study revealed that elevated summer geopotential height, no visible anticyclonic center, reduced high cloud cover, and low solar radiation with higher humidity contributed to climatic extremes in Bangladesh. The nexus between NDVI and climatic extremes established in this study indicated that increasing warm temperature extremes due to global warming might have severe implications on Bangladesh's ecology and the environment in the future