CD38 expression on CD8+ cells—Its influence on development of tuberculosis in HIV positive individuals

CD38 expression on CD8+ cells seems to correlate well with HIV viral-loads, while the ex-pression levels are thought to be low in patients with tuberculosis. This study aimed at determining the levels of CD38 expression in HIV+ individuals who develop tuberculosis. Expression levels of CD8 and CD38 were analysed in peripheral blood collected from HIV (73), TB (32), HIV-TB (31) and healthy controls (20). The percentage of CD8+/CD38+ cells significantly increased during the first few years of seropositivity and decreased during 5 - 6 years. A decline in the expression of CD38, especially on CD8+ cells in a HIV+ individual within first 2 years of seropositivity, may be indicative of susceptibility to tuberculosis. This observation was reiterated when two patients developed TB during follow-up. CD38 on CD8 cells could perhaps be useful as an early biomarker for tuberculosis in HIV-positive individuals.

Diversity Analysis in Selected Non-basmati Scented Rice Collection

Diversity analysis among 23 rice varieties including 16 non-basmati scented accessions, 5 basmati accessions and 2 non-scented accessions was performed by random amplified polymorphic DNA （RAPD） and inter-simple sequence repeat （ISSR） marker systems. The varieties analyzed by 11 RAPD and 8 ISSR primers yielded an average of 65% and 80% polymorphism, respectively. The average number of polymorphic bands generated per RAPD primer was 6 and per ISSR primer was 5.87. RAPD and ISSR data analysis individually could not segregate basmati and non-basmati scented rice accessions. However, the analysis using a combined data could group basmati and non-basmati scented rice accessions separately. The bands present specifically among three accessions of non-basmati scented rice were also identified. The study revealed a high genetic diversity among non-basmati scented rice accessions.

Construction of Genetic Linkage Map of Bread Wheat (Triticum aestivum L.) Using an Intervarietal Cross and QTL Map for Spike Related Traits

Most often a genetic linkage map is prepared using populations obtained from two highly diverse genotypes. However, the markers from such a map may not be useful in a breeding program as these markers may not

Amylotrophic Lateral Sclerosis-Like Motor Impairment in Prion Diseases

Neurodegenerative diseases are collective diseases that affect different parts of the brain with common or distinct disease phenotype. In almost all of the Prion diseases, motor impairments that are characterized by motor derangement, apathy, ataxia, and myoclonus are documented and again are shared by motor neuron diseases (MND). Proteins such as;B-Cell lymphoma 2 (BCL2), Copper chaperone for superoxide dismutase (CCS), Amyloid beta precursor protein (APP), Amyloid Precursor-Like Protein1/2 (APLP1/2), Catalase (CAT), and Stress induced phosphoprotein 1 (STIP1), are common interactomes of Prion and superoxide dismutase 1 (SOD1). Although there is no strong evidence to show the interaction of SOD1 and Prion, the implicated common interacting proteins indicate the potential bilateral interaction of those proteins in health and disease. For example, down-regulation of Heat shock protein A (HSPA5), a Prion interactome, increases accumulation of misfolded SOD1 leading to MND. Loss of Cu uptake function disturbs normal function of CCS. Over-expressed proteasome subunit alpha 3 (PSMA3) could fatigue its normal function of removing misfolded proteins. Studies showed the increase in CAT and lipid oxidation both in Prion-knocked out animal and in catalase deficiency cases. Up regulation, down regulation or direct interaction with their interactomes are predicted molecular mechanisms by which Prion and SOD exert their effect. The loss of protective function or the gain of a novel toxic property by the principal proteins is shared in Prion and MND. Thus, it might be possible to conclude that the interplay of proteins displayed in both diseases could be a key phenomenon in motor dysfunction development.

Biogenic Amines as Biomarkers for Neurotoxicity

There has been a surge of interest over the past several years in the use of neurochemical endpoints to contribute to our understanding of the mechanism of action of neurotoxicants. In our present presentation, two biogenic amine systems were selected as examples of biomarkers for neurotoxicity. To investigate these neurochemical endpoints, two prototype neurotoxicants were evaluated in experimental animals. One agent, reserpine, was used to assess developmental neurotoxicity and administered prenatally, while the other, MDMA, was used in the adult animal. The neurochemical biomarkers measured were dopamine, serotonin, and their metabolite (DOPAC and 5-HIAA) concentrations by HPLC/EC and dopamine receptor binding by radioligand receptor techniques. A review of the background, experimental design, and results are presented in this article. Our findings indicate that components of the biogenic amine systems can be used as sensitive neurochemical biomarkers of neurotoxicity. These neurochemical biomarkers can be correlated with neuropathological and behavioral biomarkers to aid in the understanding of mechanisms of neurotoxicity.

Deciphering the molecular and physiological connections between obesity and breast cancer

Obesity is associated with the higher risk of breast cancer in postmenopausal women.The leptin signaling pathway is recognized to primarily regulate energy balance and associated with breast cancer.Furthermore,the estrogen signaling pathway plays a critical role in breast carcinogenesis.In this review,we discuss how obesity is linked to breast cancer via cross-talk of leptin and estrogen pathways.

Machine learning approach for label-free rapid detection and identification of virus using Raman spectra

Objective:The objective of this study was to develop a robust method for rapid detection and identification of the virus based on Raman spectroscopy combined with machine learning approach.Methods:We have used saliva spiked with different bacterial viruses such as P1 Phage,M13 Phage,and Lambda Phage,for demonstrating the utility of this method for virus detection.The Raman spectra collected from a large number of independent samples,each of different phages with and without saliva were used to train a supervised convolutional neural network(CNN)with its hyperparameters optimized by Bayesian optimization.The CNN method was not only able to detect the presence of a phage but was also able to identify the phage type using unprocessed Raman spectra having high noise.In addition,a semi-supervised auto-encoder was utilized for differentiating healthy saliva from saliva spiked with phages thereby making it possible to detect the presence of phages in saliva samples.Results:The CNN could identify the virus with an accuracy of 98.86%based on ten-fold cross-validation,precision of 98.8%,recall of 98.7%,and F1 score of 98.7%.The area under the curve of receiver operating characteristic curve was 0.99.Autoencoder was capable of differentiating healthy saliva from the virus spiked saliva with an accuracy of 99.7%in a semi-supervised manner.Thus,Raman spectroscopy coupled with machine learning approach was able to directly detect and identify the virus without consuming time for lengthy sample processing.Conclusion:A robust method based on Raman spectroscopy coupled with machine learning may be capable of detection and identification of the virus even from the signal with low intensity and high noise.This label-free method is fast,sensitive,specific,and cost effective.

The mTOR pathway in the antiphospholipid syndrome

This perspective discussed the available evidence on the involvement of mTOR pathway in antiphospholipid syndrome(APS),from the aspects of endothelial cells,platelets,monocytes and anti-phospholipid antibodies(PLs),which may lead to future therapeutic applications of mTOR inhibition in APS.

Histone deacetylase inhibitor trichostatin A induced caspase-independent apoptosis in human gastric cancer cell

Background Histone deacetylase inhibitors （HDACIs） have been reported to induce apoptosis in cancer cells. The effects of trichostatin A （TSA） on gastric cancer cells have not been well characterized. This study was aimed to explore the effects and mechanisms of TSA on human gastric cancer SGC-7901 cells. Methods The cells were treated with TSA and analyzed by cell proliferation assay, Western blot, TUNEL assay, flow cytometry by fluorescein isothiocyanate （FITC） conjugated with Annexin V and PI staining, immunofluorescence analysis, analysis of subcellular fractionation, gene chips and real time polymerase chain reaction （PCR）. Results TSA could inhibit cell growth and induced apoptosis in gastric cancer SGC-7901 cells through the regulation of apoptosis-related genes, such as Bcl-2, Bax and survivin. Further study indicated that the pan-caspase inhibitor z-VAD-fmk did not inhibit the apoptosis induced by TSA, and we did not observe the cleavage of poly ADP ribose polymerase （PARP） after TSA treatment too. In addition, apoptosis inducing factor （AIF） and EndoG were found to translocate from mitochondria to nucleus in the immunofluorescence assay and the Western analysis of subcellular fractionation confirmed the result of immunofluorescence assay. Conclusions The apoptosis induced by TSA in gastric cancer SGC-7901 cells involves a caspase-independent pathway.

Genetic approach to track neural cell fate decisions using human embryonic stem cells

With their capability to undergo unlimited self-renewal and to differentiate into all cell types in the body, human embryonic stem cells （hESCs） hold great promise in human cell therapy. However, there are limited tools for easily identifying and isolating live hESC-derived cells. To track hESC-derived neural progenitor cells （NPCs）, we applied homologous recombination to knock-in the mCherry gene into the Nestin locus of hESCs. This facilitated the genetic labeling of Nestin positive neural progenitor cells with mCherry. Our reporter system enables the visualization of neural induction from hESCs both in vitro （embryoid bodies） and in vivo （ter- atomas）. This system also permits the identification of different neural subpopulations based on the intensity of our fluorescent reporter. In this context, a high level of mCherry expression showed enrichment for neural progenitors, while lower mCherry corresponded with more committed neural states. Combination of mCherry high expression with cell surface antigen staining enabled further enrichment of hESC-derived NPCs. These mCherry＊ NPCs could be expanded in culture and their differentiation resulted in a down-regulation of mCherry consistent with the loss of Nestin expression. Therefore, we have developed a fluorescent reporter system that can be used to trace neural differentiation events of hESCs.

Immunoelectron Microscopy for Locating Calvin Cycle Enzymes in the Thylakoids of Synechocystis 6803

Unicellular cyanobacteria Synechocystis 6803 were fixed using high-pressure freezing （HPF） and freeze substitution without any chemical cross-linkers. Immunoelectron microscopy of these cells showed that five sequential enzymes of the Calvin cycle （phosphoriboisomerase, phosphoribulokinase, ribulose-1,5-bisphosphate carboxylase/oxygenase （RuBisCO）, 3-phosphoglyceratekinase and glyceraldehyde-3-phosphate dehydrogenase） and the catalytic portion of the chloroplast H^＋-ATP synthase （CF1） are located adjacent to the thylakoid membranes. Cell-free extracts of Synechocystis were processed by ultracentrifugation to isolate thylakoid fractions sedimenting at 40 000, 90 000, and 150 000 g. Among these, the 150 000-g fraction showed the highest linked activity of the above five sequential Calvin cycle enzymes and also the highest coordinated activity of light and dark reactions as assessed by ribose-5-phosphate （R-5-P） ＋ADP dependent CO2 fixation. Immunogold labeling of this membrane fraction confirmed the presence of the above five enzymes as well as the catalytic portion of the CF1 ATP synthase. Notably, the protein A-gold labeling of the thylakoids was observed without use of chemical cross-linkers and in spite of the normal washing steps used during standard immunolabeling. The results showed that soluble Calvin cycle enzymes might be organized along the thylakoid membranes.

Differential alterations of positive and negative regulators of beta catenin enhance endogenous expression and activity of beta catenin in A549 non small cell lung cancer(NSCLC)cells

Beta catenin has been well documented in previous studies to be involved in non small cell lung cancer(NSCLC).Beta catenin abundance and transcriptional activity are significantly regulated by several factors.Though it is well known that Akt and Gsk3 beta are respective positive and negative regulators of beta catenin,however,no single study has so far documented how the expression and activity of both positive as well as negative regulators play favorable role on beta catenin expression and activity in NSCLC.In this study,we compared expression and activity of beta catenin and its regulators in normal lung cell WI38 and NSCLC cell A549 by western blot,qRT-PCR and luciferase assay.We observed that beta catenin positive regulators(Akt and Hsp90)and negative regulators(Gsk3 beta and microRNA-214)have differential expression and/or activity in NSCLC cell A549.However the differentially altered statuses of both the positive and negative regulators rendered cumulative positive effect on beta catenin expression and activity in A549.Our study thus suggests that chemotherapeutic modulations of regulating factors are crucial when abrogation and/or inhibition of key oncogenic proteins are necessary for cancer chemotherapy.

Progress and bottleneck in induced pluripotency

With their capability to undergo unlimited self-renewal and to differentiate into all cell types in the body,induced pluripotent stem cells(iPSCs),reprogrammed from somatic cells of individual patients with defined factors,have unlimited potential in cell therapy and in modeling complex human diseases.Significant progress has been achieved to improve the safety of iPSCs and the reprogramming efficiency.To avoid the cancer risk and spontaneous reactivation of the reprogramming factors associated with the random integration of viral vectors into the genome,several approaches have been established to deliver the reprogramming factors into the somatic cells without inducing genetic modification.In addition,a panel of small molecule compounds,many of which targeting the epigenetic machinery,have been identified to increase the reprogramming efficiency.Despite these progresses,recent studies have identified genetic and epigenetic abnormalities of iPSCs as well as the immunogenicity of some cells derived from iPSCs.In addition,due to the oncogenic potential of the reprogramming factors and the reprogramming-induced DNA damage,the critical tumor suppressor pathways such as p53 and ARF are activated to act as the checkpoints that suppress induced pluripotency.The inactivation of these tumor suppression pathways even transiently during reprogramming processes could have significant adverse impact on the genome integrity.These safety concerns must be resolved to improve the feasibility of the clinic development of iPSCs into human cell therapy.