Detection of early Alzheimer's disease-like molecular alterations in a mouse model expressing human ApoE4.

The E4 allele of apolipoprotein E (ApoE4) is a key genetic risk factor for late-onset Alzheimer's disease (AD), increasing the risk of developing the disease by up to three-fold. However, the mechanisms by which ApoE4 contributes to AD pathogenesis are poorly understood. Here, we utilize a mouse model expressing either human ApoE3 or human ApoE4 to examine the effects of the E4 allele on a wide range of genetic and molecular pathways that are altered in early AD pathology. We demonstrate that ApoE4-expressing mice begin to show early differential expression of multiple genes, leading to alterations in downstream pathways related to neural cell maintenance, insulin signaling, amyloid processing and clearance, and synaptic plasticity. These alterations may result in the earlier accumulation of pathological proteins such as ß-amyloid that may build up within cells, leading to the accelerated degeneration of neurons and astrocytes as observed in ApoE4-positive individuals. We also examine the metabolic effects associated with a high-fat diet (HFD) in male ApoE4-expressing mice compared with regular chow diet (RD) fed mice at different ages. We found that young ApoE4-expressing mice fed HFD developed metabolic disturbances, such as elevated weight gain, blood glucose, and plasma insulin levels that cumulatively have been observed to increase the risk of AD in humans. Taken together, our results reveal early pathways that could mediate ApoE4-related AD risk and may help identify more tractable therapeutic targets for treating ApoE4-associated AD.

A Cell Culture-Adapted Vaccine Virus against the Current African Swine Fever Virus Pandemic Strain.

African swine fever virus (ASFV) causes a virulent, deadly infection in wild and domestic swine and is currently causing a pandemic covering a contiguous geographical area from Central and Eastern Europe to Asia. No commercial vaccines are available to prevent African swine fever (ASF), resulting in devastating economic losses to the swine industry. The most advanced vaccine candidates are live attenuated strains developed using a genetically modified virulent parental virus. Recently, we developed a vaccine candidate, ASFV-G-ΔI177L, by deleting the I177L gene from the genome of the highly virulent ASFV pandemic strain Georgia (ASFV-G). ASFV-G-ΔI177L is safe and highly efficacious in challenge studies using parental ASFV-G. Large-scale production of ASFV-G-ΔI177L has been limited because it can replicate efficiently only in primary swine macrophages. Here, we present the development of an ASFV-G-ΔI177L derivative strain, ASFV-G-ΔI177L/ΔLVR, that replicates efficiently in a stable porcine cell line. In challenge studies, ASFV-G-ΔI177L/ΔLVR maintained the same level of attenuation, immunogenic characteristics, and protective efficacy as ASFV-G-ΔI177L. ASFV-G-ΔI177L/ΔLVR is the first rationally designed ASF vaccine candidate that can be used for large-scale commercial vaccine manufacture. IMPORTANCE African swine fever is currently causing a pandemic resulting in devastating losses to the swine industry. Experimental ASF vaccines rely on the production of vaccine in primary swine macrophages, which are difficult to use for the production of a vaccine on a commercial level. Here, we report a vaccine for ASFV with a deletion in the left variable region (LVR). This deletion allows for growth in stable cell cultures while maintaining the potency and efficacy of the parental vaccine strain. This discovery will allow for the production of an ASF vaccine on a commercial scale.

Structural Glycoprotein E2 of Classical Swine Fever Virus Critically Interacts with Host Protein Torsin-1A during the Virus Infectious Cycle.

The classical swine fever virus (CSFV) glycoprotein E2 is the major structural component of the virus particle. E2 is involved in several functions, such as virus adsorption to the cell, the elicitation of protective immune responses, and virus virulence in swine. Using a yeast two-hybrid system, we previously identified the swine host protein Torsin-1A, an ATPase protein residing in the endoplasmic reticulum and inner nucleus membrane of the cell, as a specific binding partner for E2. The interaction between Torsin-1A and E2 proteins was confirmed to occur in CSFV-infected swine cells using three independent methods: coimmunoprecipitation, confocal microscopy, and proximity ligation assay (PLA). Furthermore, the E2 residue critical to mediate the protein-protein interaction with Torsin-1A was identified by a reverse yeast two-hybrid assay using a randomly mutated E2 library. A recombinant CSFV E2 mutant protein with a Q316L substitution failed to bind swine Torsin-1A in the yeast two-hybrid model. In addition, a CSFV infectious clone harboring the E2 Q316L substitution, although expressing substantial levels of E2 protein, repetitively failed to produce virus progeny when the corresponding RNA was transfected into susceptible SK6 cells. Importantly, PLA analysis of the transfected cells demonstrated an abolishment of the interaction between E2 Q316L and Torsin-1A, indicating a critical role for that interaction during CSFV replication.IMPORTANCE Structural glycoprotein E2 is an important structural component of the CSFV particle. E2 is involved in several virus functions, particularly virus-host interactions. Here, we characterized the interaction between CSFV E2 and swine protein Torsin-1A during virus infection. The critical amino acid residue in E2 mediating the interaction with Torsin-1A was identified and the effect of disrupting the E2-Torsin-1A protein-protein interaction was studied using reverse genetics. It is shown that the amino acid substitution abrogating E2-Torsin-1A interaction constitutes a lethal mutation, demonstrating that this virus-host protein-protein interaction is a critical factor during CSFV replication. This highlights the potential importance of the E2-Torsin-1A protein-protein interaction during CSFV replication and provides a potential pathway toward blocking virus replication, an important step toward the potential development of novel virus countermeasures.

Assessing immuno-expression of p53 protein and TP 53 gene amplification in histologically negative surgical margins of oral squamous cell carcinoma patients and normal oral mucosa.

OBJECTIVE: To assess and compare the immuno-expression of p53 and TP 53 gene amplification and correlate local recurrence and survival in histologically negative surgical margins of oral squamous cell carcinoma (OSCC) with normal oral mucosa. METHODS: Forty formalin-fixed paraffin-embedded tissue blocks of HNMs of OSCC and 40 normal oral mucosa samples were analyzed for p53 immunostaining and TP 53 gene amplification by PCR. RESULTS: Significantly, higher positivity was noted with p53 immuno-expression, TP53 gene amplification, and combined p53 and TP53 expression in the study group compared to the control group (C0.05). Most cases that were positive for p53 immuno-expression, TP 53 gene amplification, and combined p53 and TP53 expression showed local recurrence and poor survival. Kaplan-Meier survival analysis showed that subjects with TP53 and combined p53 and TP53 positivity had decreased survival rate than their negative counterparts. CONCLUSION: Detection of p53 in HNMs of OSCC can be used as a biomarker to identify patients at a higher risk of developing local recurrence and to predict survival. CLINICAL RELEVANCE: Combined p53 and TP 53 assessment may be more reliable for predicting LR to help clinicians and surgeons in treatment planning.

Long-Term Variation in Carbonaceous Components of PM2.5 from 2012 to 2021 in Delhi.

Carbonaceous species [organic carbon (OC), elemental carbon (EC), elemental matter (EM), primary organic carbon (POC), secondary organic carbon (SOC), total carbon (TC), and total carbonaceous matter (TCM)] of PM2.5 were analyzed to study the seasonal variability and long-term trend of carbonaceous aerosols (CAs) in megacity Delhi, India from January, 2012 to April, 2021. The average concentrations (± standard deviation) of PM2.5, OC, EC, TC, EM, TCM, POC and SOC were 127 ± 77, 15.7 ± 11.6, 7.4 ± 5.1, 23.1 ± 16.5, 8.2 ± 5.6, 33.3 ± 23.9, 9.3 ± 6.3 and 6.5 ± 5.3 µg m-3, respectively during the sampling period (10-year average). The average CAs accounted for 26% of PM2.5 concentration during the entire sampling period. In addition, the seasonal variations in PM2.5, OC, EC, POC, SOC, and TCM levels were recorded with maxima in post-monsoon and minima in monsoon seasons. The linear relationship of OC and EC, OC/EC and EC/TC ratios suggested that the vehicular emissions (VE), fossil fuel combustion (FFC) and biomass burning (BB) are the major sources of CAs at megacity Delhi, India.

A novel bicistronic DNA vaccine with enhanced protective immune response against Bacillus anthracis through DNA prime-protein boost vaccination approach.

Anthrax, by Bacillus anthracis, remains a dreadful fatal hazard worldwide. The currently used anthrax vaccines are plagued by numerous issues that limit their widespread use. As an immunization approach targeting both extracellular antigens and toxins of B. anthracis may achieve better sterile immunity, the present investigation designed a bicistronic secretory anti-anthrax DNA vaccine targeting immune response against toxin and cells. The efficacy of the vaccine was compared with monocistronic DNA vaccines and the currently used anthrax vaccine. For this, mice were immunized with the developed vaccine containing pag (encoding protective antigen to block toxin) and eag genes (encoding EA1 to target cells) of B. anthracis through DNA-prime/Protein-boost (D/P) and DNA prime/DNA-boost (D/D) approaches. There was a >2 and > 5 fold increase in specific antibody level by D/D and D/P approaches respectively, on 42nd days post-immunization (dpi). Serum cytokine profiling showed that both Th1 and Th2 immune responses were elicited, with more Th2 responses in D/P strategy. More importantly, challenge with 100 times LD50 of B. anthracis at 42nd dpi exhibited maximum cumulative survival (83.33 %) by bicistronic D/P approach. Remarkably, immunization with EA1 delayed mortality onset in infection. The study forms the first report on complement-dependent bactericidal activity of antiEA1 antibodies. In short, co-immunization of PA and EA1 through the developed bicistronic DNA vaccine would be an effective immunization approach in anthrax vaccination. Further, D/P strategy could enhance vaccine-induced immunity against B. anthracis. Altogether, the study generates certain critical insights having direct applications in next-generation vaccine development against anthrax.

Patient Safety in the Operating Room During Urologic Surgery: The OR Black Box Experience.

PURPOSE: To mitigate intraoperative adverse events, it is important to understand the context in which these errors occur. The purpose of this study is to characterize the IAEs and potential distractions that occur in minimally invasive urologic procedures. METHODS: We conducted a prospective cohort study in patients undergoing laparoscopic urologic surgery at an academic health center. The OR Black Box, a unique technology system which captures video and audio recordings of the operating room as well as the operative field, was used to collect data regarding procedure type, critical step, IAEs, and distractions. RESULTS: Of a total of 80 cases analyzed, the majority of these cases were partial nephrectomy (n = 36; 45%), radical nephrectomy (n = 20; 25%), and adrenalectomy (n = 4; 5%). Across all cases, there were a total of 138 clinically significant IAEs, 10 of which (14%) were of the highest severity (five on the SEVerity of intraoperative Events and Rectification Tool (SEVERE) matrix). Of these, 70 (51%) occurred during an a priori defined critical step of the operation. Distractions were common across all cases. The median rate of external communication per case was 16 events (IQR 11-22); and per critical step was 4 (IQR 2.75-8), while median room traffic per case was 65 entries/exits (IQR 42-76); and per critical step was 17 (IQR 10-65). CONCLUSION: Our data demonstrate that IAEs occur frequently during all phases of the operation at hand. Future study will be required to examine the role of distractions and IAE as well as IAE and their relationship to post-operative clinical outcomes.

MicroRNA-related markers associated with corpus luteum tropism in buffalo (Bubalus bubalis).

The study was undertaken to decipher the microRNA (miRNA) related markers associated with corpus luteum (CL) tropism in buffalo. The data obtained from deep sequencing of CL tissue from different physiological stages was mined in silico for the identification of miRNA-related markers (SSR & SNP). From the present study, 5 annotated and 176 unannotated miRNA were deduced while comparing with Bos taurus genome. In addition, 4 SSRs and 9 SNPs were deduced from the miRNA sequences. These SSRs were on the genes viz. Eukaryotic translation initiation factor 1-like, myocyte enhancer factor 2A, beta casein, T cell receptor gamma cluster 1. The SNP positions on genes viz. PYGO1 (Pygopus family PHD finger 1), LOC100337244 (Multidrug resistance-associated protein 4), FTH1 (Ferritin heavy chain 1), LOC788634 (BOLA class I histocompatibility antigen), PLXND1 (Plexin D1) and UBC (Ubiquitin C) show that these genes play critical role in CL tropism during estrous cycle in buffalo.

Structural Glycoprotein E2 of Classical Swine Fever Virus Interacts with Host Protein Dynactin Subunit 6 (DCTN6) during the Virus Infectious Cycle.

The E2 protein in classical swine fever (CSF) virus (CSFV) is the major virus structural glycoprotein and is an essential component of the viral particle. E2 has been shown to be involved in several functions, including virus adsorption, induction of protective immunity, and virulence in swine. Using the yeast two-hybrid system, we previously identified a swine host protein, dynactin subunit 6 (DCTN6) (a component of the cell dynactin complex), as a specific binding partner for E2. We confirmed the interaction between DCTN6 and E2 proteins in CSFV-infected swine cells by using two additional independent methodologies, i.e., coimmunoprecipitation and proximity ligation assays. E2 residues critical for mediating the protein-protein interaction with DCTN6 were mapped by a reverse yeast two-hybrid approach using a randomly mutated E2 library. A recombinant CSFV mutant, E2ΔDCTN6v, harboring specific substitutions in those critical residues was developed to assess the importance of the E2-DCTN6 protein-protein interaction for virus replication and virulence in swine. CSFV E2ΔDCTN6v showed reduced replication, compared with the parental virus, in an established swine cell line (SK6) and in primary swine macrophage cultures. Remarkably, animals infected with CSFV E2ΔDCTN6v remained clinically normal during the 21-day observation period, which suggests that the ability of CSFV E2 to bind host DCTN6 protein efficiently during infection may play a role in viral virulence.IMPORTANCE Structural glycoprotein E2 is an important component of CSFV due to its involvement in many virus activities, particularly virus-host interactions. Here, we present the description and characterization of the protein-protein interaction between E2 and the swine host protein DCTN6 during virus infection. The E2 amino acid residues mediating the interaction with DCTN6 were also identified. A recombinant CSFV harboring mutations disrupting the E2-DCTN6 interaction was created. The effect of disrupting the E2-DCTN6 protein-protein interaction was studied using reverse genetics. It was shown that the same amino acid substitutions that abrogated the E2-DCTN6 interaction in vitro constituted a critical factor in viral virulence in the natural host, domestic swine. This highlights the potential importance of the E2-DCTN6 protein-protein interaction in CSFV virulence and provides possible mechanisms of virus attenuation for the development of improved CSF vaccines.

Thickness uniformity measurements and damage threshold tests of large-area GaAs/AlGaAs crystalline coatings for precision interferometry.

Precision interferometry is the leading method for extremely sensitive measurements in gravitational wave astronomy. Thermal noise of dielectric coatings poses a limitation to the sensitivity of these interferometers. To decrease coating thermal noise, new crystalline GaAs/AlGaAs multilayer mirrors have been developed. To date, the surface figure and thickness uniformity of these alternative low-loss coatings has not been investigated. Surface figure errors, for example, cause small angle scattering and thereby limit the sensitivity of an interferometer. Here we measure the surface figure of highly reflective, substrate-transferred, crystalline GaAs/AlGaAs coatings with a custom scanning reflectance system. We exploit the fact that the reflectivity varies with the thickness of the coating. To increase penetration into the coating, we used a 1550 nm laser on a highly reflective coating designed for a center wavelength of 1064 nm. The RMS thickness variation of a two inch optic was measured to be 0.41 ± 0.05 nm. This result is within 10% of the thickness uniformity, of 0.37 nm RMS, achieved with ion-beam sputtered coatings for the aLIGO detector. We additionally measured a lower limit of the laser induced damage threshold of 64 MW/cm 2 for GaAs/AlGaAs coatings at a wavelength of 1064 nm.

Design and rationale of the atrial fibrillation occurring transiently with stress (AFOTS) incidence study.

BACKGROUND: Atrial fibrillation (AF) is often detected for the first time in patients hospitalized for medical illness or non-cardiovascular surgery. AF occurring transiently with stress (AFOTS) describes this manifestation of AF, which may either be the result of a non-cardiac stressor, or existing paroxysmal AF that was not previously detected. Current estimates of AFOTS incidence are imprecise: ranging from 1 to 44%, owing to the marked heterogeneity in patient populations, identification and methods used to detect AFOTS. METHODS: The prospective, two-centre epidemiological AFOTS Incidence study will enroll 250 consecutive participants without a history of AF but with at increased risk of AF (Age ≥ 65 or >50 with one risk factor for AF) admitted to intensive care units (ICUs) for medical illness or non-cardiac surgery. Upon admission, participants will wear an ECG patch monitor that will remain in place for 14 days, or until discharge from hospital. Patients' consent to participation is deferred for up to 72 h after admission. The primary endpoint is the incidence of AF lasting ≥30 s. The study is powered to detect an AF incidence of 17% ±â€¯5%. RESULTS: We conducted a vanguard feasibility study, and 55 participants have completed participation. The median duration of monitoring was seven days. AF was detected by the clinical team in 8 participants (14%; 95% Confidence Interval 7-26%). CONCLUSIONS: The AFOTS Incidence study will employ a systematic and highly sensitive protocol for detecting AFOTS in medical illness and non-cardiac surgery ICU patients. This study is feasible and will provide a reliable estimate of the true incidence of AFOTS in this population.

Physiological responses of soybean (Glycine max (L.) Merrill) cultivars to copper excess.

Successive applications of copper fungicides on vines have resulted in increased copper content in vineyard soils over the years. This high copper content has affected the growth of young vines in eradicated vineyards. Thus, the cultivation of annual species for a few years is an alternative to copper phytostabilization, because it would be a good way to decrease copper availability to plants. The aim of this study was to evaluate the physiological responses of different soybean cultivars to copper concentration increase. Four different soybean cultivars were grown under three copper concentrations: 0.5, 20 and 40 µM in nutrient solution. The main outcomes of this study were: i) Cultivar M 6410 IPRO recorded the highest photosynthetic rate when plants were exposed to 40 µM of copper in the nutrient solution; ii) plants in cultivar M 6410 IPRO accumulated large copper concentrations in their roots although did not decrease the root dry mass, possibly due to the higher superoxide dismutase activity; iii) cultivar DM 5958 RSF IPRO recorded drastically reduced photosynthetic rate and dry mass production due to copper excess. We conclude that each cultivar responded differently to the excess of copper, but none of them showed tolerance to it.

Relationship between microRNA-206 plasma levels with the severity of coronary artery conflicts in patients with coronary artery disease.

OBJECTIVES: The aim of this study was to evaluate the possible association of miR-206 serum as an indicator of diagnosis in patients with coronary artery disease. METHODS: In this study, 100 patients with coronary artery disease who had angiography and vascular transplantation were selected and evaluated. Extraction of microRNAs from peripheral blood plasma was performed using an exclusive microRNA extraction kit. Then the cDNA synthesis of the target microRNA was performed and its concentration and purity were evaluated. The expression level of miR-206 was performed using the real-time PCR technique and the SYBER Green method, using U6 snRNA as an internal control. In order to analyze the amount of microRNA expression and the significance of the patient sample, the t­test was used to compare the control sample. Also, Pearson correlation coefficient test was used to determine the relationship between the expression level of microRNAs. RESULTS: The results showed a positive correlation between miR-206 expression and coronary artery disease.While the average expression of 1 ± 0.18 in the control sample was increased to 8.76 according to the severity of involvement in the patient, the relative expression of miR-206 in the CAD + group was significantly increased compared to the control (p < 0. 03). CONCLUSIONS: It appears that miR-206 can be considered as an indicator of coronary endothelial cell function. As such, it can be used as a biomarker for prognosis and in controlling the treatment for coronary artery disease (Tab. 2, Fig. 3, Ref. 20).

Permcath - A Vascular Access for Hemodialysis, Our Experience in Last Two Years.

Background The double lumen tunneled catheter (Permcath) is mostly used as an alternative access, not as a temporary access in End Stage Renal Disease patients requiring hemodialysis. If there is no possibility of other access modalities, failed or unable to create native arteriovenous fistula (AVF), Permcath can be a very good alternative. Objective To find the indications, complications and results of Permcath insertion. Method We reviewed the results of 92 Permcath inserted under ultrasound guidance in two different hospitals, 45 in Sahid Dharma Bhakta National Transplant Center (SDNTC), Bhaktapur and 47 in Nidan Hospital Pvt. Ltd., Lalitpur from April 2016 to April 2018 retrospectively. Result We had inserted 55 Permcath (59.78%) in right internal jugular vein (IJV), 25 (27.17%) in left internal jugular vein and 12(13.04%) in femoral vein. In terms of major complications, two (2.17%) patients had profound hypotension, bradycardia and cardiac arrest due to left internal jugular vein tear. Three patients (3.26%) died within a week due to septicemia and 23 patients (25%) died with multiple causes within one year. Of the cases, till now in 39 cases (42.39%) Permcath has been removed. Major reasons of removal of Permcath are post renal transplant in 18 cases (19.57%), Arterio Venous Fistula maturation in 13 cases (14.13%), Infection in six patients (6.52%) and non functioning Permcath in two patients (2.17%). Conclusion Permcath remains a reliable method for short term vascular access, hence can be used as a bridge to renal transplant or arteriovenous fistula maturation.

Chemically characterised extract of Saraca asoca improves the sexual function in male Wistar rats.

In this study, methanolic extract of Saraca asoca bark was evaluated for its aphrodisiac potential using male and female Wistar albino rats. Male rats were dosed daily for 54 days at a dose of 100 mg/kg p.o. Sexual activity of male rats was assessed after 14, 28, 42 and 54 days of the study. Male rats were placed in a glass chamber lit with a dim red light (10W) followed by the introduction of sexually receptive female rats in a ratio of 1:1. Improvement in sexual behaviour of male rats was characterised by an increase in both mount frequency and intromission frequency and decrease or reduction in mount latency and intromission latency compared to normal control. After completion of the study, the effect of the S. asoca extract on sperm count, sperm motility and sperm morphology was also assessed. The extract of S. asoca bark was found to be safe as it did not affect these sperm parameters. From this study, it was found that methanolic extract of S. asoca bark plays a role in enhancing sexual behaviour and potential without causing reproductive toxicity.

Rapid analysis of pharmaceutical drugs using LIBS coupled with multivariate analysis.

Type 2 diabetes drug tablets containing voglibose having dose strengths of 0.2 and 0.3 mg of various brands have been examined, using laser-induced breakdown spectroscopy (LIBS) technique. The statistical methods such as the principal component analysis (PCA) and the partial least square regression analysis (PLSR) have been employed on LIBS spectral data for classifying and developing the calibration models of drug samples. We have developed the ratio-based calibration model applying PLSR in which relative spectral intensity ratios H/C, H/N and O/N are used. Further, the developed model has been employed to predict the relative concentration of element in unknown drug samples. The experiment has been performed in air and argon atmosphere, respectively, and the obtained results have been compared. The present model provides rapid spectroscopic method for drug analysis with high statistical significance for online control and measurement process in a wide variety of pharmaceutical industrial applications.

Actinomycetes: an unexplored microorganisms for plant growth promotion and biocontrol in vegetable crops.

Actinomycetes, a Gram positive bacteria, well reported as a source of antibiotics, also possess potential to control various plant pathogens, besides acting as plant growth promoting agent. Chemicals in different forms are extensively being used in vegetable farming, adversely affecting the environment and consumer health. Microbial agent like actinomycetes can substantially replace these harmful chemicals, and have now started finding a place as an important input in to farming practices. Only selected vegetable crops belonging to 11 different families have been explored with use of actinomycetes as biocontrol and plant growth promoting agent till now. It provides ample opportunities to vegetable researchers, to further explore with use of this very important group of microorganisms, in order to achieve even higher production level of safe vegetables. Mycostop and Actinovate are two actinomycetes based formulations globally available for use in vegetable farming as a substitute for chemical formulations. Present review article has summarized the literature available on use of actinomycetes in vegetable farming. Existing wide gap in knowledge, and potential thrust areas for future research have also been projected.

Exonal switch down-regulates the expression of CD5 on blasts of acute T cell leukaemia.

To date, CD5 expression and its role in acute T cell lymphoblastic leukaemia (T-ALL) have not been studied closely. We observed a significant reduction in surface expression of CD5 (sCD5) on leukaemic T cells compared to autologous non-leukaemic T cells. In this study, we have shown the molecular mechanism regulating the expression and function of CD5 on leukaemic T cells. A total of 250 patients suffering from leukaemia and lymphoma were immunophenotyped. Final diagnosis was based on their clinical presentation, morphological data and flow cytometry-based immunophenotyping. Thirty-nine patients were found to be of ALL-T origin. Amplification of early region of E1A and E1B transcripts of CD5 was correlated with the levels of surface and intracellular expression of CD5 protein. Functional studies were performed to show the effect of CD5 blocking on interleukin IL-2 production and survival of leukaemic and non-leukaemic cells. Lack of expression of sCD5 on T-ALL blasts was correlated closely with predominant transcription of exon E1B and significant loss of exon E1A of the CD5 gene, which is associated with surface expression of CD5 on lymphocytes. High expression of E1B also correlates with increased expression of cytoplasmic CD5 (cCD5) among leukaemic T cells. Interestingly, we observed a significant increase in the production of IL-2 by non-leukaemic T cells upon CD5 blocking, leading possibly to their increased survival at 48 h. Our study provides understanding of the regulation of CD5 expression on leukaemic T cells, and may help in understanding the molecular mechanism of CD5 down-regulation.

Molecular epidemiology of Crimean-Congo haemorrhagic fever virus in India.

Crimean-Congo haemorrhagic fever (CCHF) is an emerging zoonotic disease in India which is prevalent in neighbouring countries. CCHF virus (CCHFV) is a widespread tick-borne virus which is endemic in Africa, Asia, Eastern Europe and the Middle East. In the present study, samples of clinically suspected human cases from different areas of northern-western India were tested for the presence of CCHFV by RT-PCR through amplification of nucleocapsid (N) gene of CCHFV. Positive samples were sequenced to reveal the prevailing CCHFV genotype(s) and phylogenetic relatedness. A phylogenetic tree revealed the emergence of diverse strains in the study region showing maximum identity with the Pakistan, Afghanistan and Iran strains, which was different from earlier reported Indian strains. Our findings reveal for the first time the emergence of the Asia 1 group in India; while earlier reported CCHFV strains belong to the Asia 2 group.