Mycotin: a lectin involved in the adherence of Mycobacteria to macrophages

Pathogenic Mycobacteria colonize host macrophages. Attachement of these organisms to macrophages is the preliminary step prior to invasion of the macrophages by the bacteria. Western blot confirmed that walls of Mycobacterium avium and Mycobacterium tuberculosis contain molecules which are immunologically related to mycotin, a lectin found in Mycobacterium smegmatis. We have demonstrated that the adherence of Mycobacteria to macrophages is significantly inhibited by anti-mycotin antibody or the mycotin-specific sugar, mannan. These observations suggest that prevention of the interaction of mycotin-related molecules on the surfaces of Mycobacteria with mannose-specific receptors on macrophages, offers an important approach for blocking attachment of pathogenic Mycobacteria to macrophages, thereby preventing infection

Noncommutative Black Hole Thermodynamics

We give a general derivation, for any static spherically symmetric metric, of the relation $T_h=\frac{\cal K}{2\pi}$ connecting the black hole temperature ($T_h$) with the surface gravity ($\cal K$), following the tunneling interpretation of Hawking radiation. This derivation is valid even beyond the semi classical regime i. e. when quantum effects are not negligible. The formalism is then applied to a spherically symmetric, stationary noncommutative Schwarzschild space time. The effects of back reaction are also included. For such a black hole the Hawking temperature is computed in a closed form. A graphical analysis reveals interesting features regarding the variation of the Hawking temperature (including corrections due to noncommutativity and back reaction) with the small radius of the black hole. The entropy and tunneling rate valid for the leading order in the noncommutative parameter are calculated. We also show that the noncommutative Bekenstein-Hawking area law has the same functional form as the usual one.Comment: LaTex, 17 pages, 2 figures, minor changes, references added, to appear in Phys. Rev.

Understanding and validating the traditional rainfall classification and forecasting system with its implication to agriculture in Kalimpong Hill of West Bengal

425-433The farmers in Kalimpong and Darjeeling hills mainly depend on agriculture for their livelihood and live in difficult geographic terrain. They devised their own weather and rainfall classification system based on local indicators. The present study was conducted in Kalimpong hill over a period of four years from 2015-2019 to understand the traditional wisdom of weather prediction and its implication in hill agriculture. Numerous surveys were conducted at villages namely, Ichey Gaon, Bong Basti, Algarah, Sangsey Basti, Lava, Loley, Kafer, Tindhurey and Gorubathan. The people classified the rainfall as Sawney Jhari, Bhadurey Jhari, Sohrasaradey jhari, Bonsho jhari, Titey jhari, Sisney Jhari, Naurathey Jhari, Chuia jhari, Faprey jhari, Bhangera jhari, Makurey jhari, Kartikey jhari, Maghe jhari, Ashwina based on time of rainfall. The farmers predicted this rainfall based on phenology of local plants, movement of animals or birds etc. It was found that the knowledge of this traditional rainfall helped them to take different farming decisions especially in scheduling irrigation for major crops. The traditional knowledge has been reviewed with 50 years climatic data and it was found that in most cases it conformed with their traditional belief

Baseline information of reproduction parameters of an amphidromous croaker Johnius coitor (Hamilton, 1822) from Ganga river basin, India with special reference to potential influence of climatic variability

Reproductive biology of female amphidromous croaker Johnius coitor (Hamilton, 1822) was studied for the first time from various freshwater stretches of Ganga river basin, India in relation to climatic variability. The species showed high spatial variation in reproductive phenology and capable of breeding during pre-monsoon, monsoon, post-monsoon and winter. Water temperature is the most crucial environmental parameter influencing gonadal maturation and breeding. Generalized additive model (GAM) models revealed water temperature near 23–25 °C as optimum and threshold GSI above 3 units necessary for breeding. Pre-spawning fitness (Kspawn50) and size at 50% maturity (LM50) benchmarked through Kaplan-Meier survival fit estimates were in the range 1.27–1.37 units and 19–24.5 cm respectively. First maturity of females was encountered at 11.4 cm within the size range 7.2–28.5 cm. Egg parameters in mature-ripe females ranged between 0.29–0.80 mm (diameter), 0.05–0.19 mg (weight) and 5687–121 849 eggs (absolute fecundity). Mapping of climate preferendum through LOESS smoothing technique hinted water temperatures 32 °C to be detrimental for attainment of pre-spawning fitness while no dependence on rainfall was observed. Based on the climato-hydrological influence on breeding and regional trends of changing climate along river Ganga, we infer minimal climate driven changes in breeding phenology of this amphidromous fish species. Results of this study may serve as baseline information for future studies assessing climate driven changes and evolutionary adaptations in croakers from river Ganga

Glassy Phase Transition and Stability in Black Holes

Black hole thermodynamics, confined to the semi-classical regime, cannot address the thermodynamic stability of a black hole in flat space. Here we show that inclusion of correction beyond the semi-classical approximation makes a black hole thermodynamically stable. This stability is reached through a phase transition. By using Ehrenfest's scheme we further prove that this is a glassy phase transition with a Prigogine-Defay ratio close to 3. This value is well placed within the desired bound (2 to 5) for a glassy phase transition. Thus our analysis indicates a very close connection between the phase transition phenomena of a black hole and glass forming systems. Finally, we discuss the robustness of our results by considering different normalisations for the correction term.Comment: v3, minor changes over v2, references added, LaTeX-2e, 18 pages, 3 ps figures, to appear in Eour. Phys. Jour.

High monocytic MDSC signature predicts multi-drug resistance and cancer relapse in non-Hodgkin lymphoma patients treated with R-CHOP

IntroductionNon-Hodgkin Lymphoma (NHL) is a heterogeneous lymphoproliferative malignancy with B cell origin. Combinatorial treatment of rituximab, cyclophsphamide, hydroxydaunorubicin, oncovin, prednisone (R-CHOP) is the standard treatment regimen for NHL, yielding a complete remission (CR) rate of 40-50%. Unfortunately, considerable patients undergo relapse after CR or initial treatment, resulting in poor clinical implications. Patient’s response to chemotherapy varies widely from static disease to cancer recurrence and later is primarily associated with the development of multi-drug resistance (MDR). The immunosuppressive cells within the tumor microenvironment (TME) have become a crucial target for improving the therapy efficacy. However, a better understanding of their involvement is needed for distinctive response of NHL patients after receiving chemotherapy to design more effective front-line treatment algorithms based on reliable predictive biomarkers.MethodsPeripheral blood from 61 CD20+ NHL patients before and after chemotherapy was utilized for immunophenotyping by flow-cytometry at different phases of treatment. In-vivo and in-vitro doxorubicin (Dox) resistance models were developed with murine Dalton’s lymphoma and Jurkat/Raji cell-lines respectively and impact of responsible immune cells on generation of drug resistance was studied by RT-PCR, flow-cytometry and colorimetric assays. Gene silencing, ChIP and western blot were performed to explore the involved signaling pathways.ResultsWe observed a strong positive correlation between elevated level of CD33+CD11b+CD14+CD15- monocytic MDSCs (M-MDSC) and MDR in NHL relapse cohorts. We executed the role of M-MDSCs in fostering drug resistance phenomenon in doxorubicin-resistant cancer cells in both in-vitro, in-vivo models. Moreover, in-vitro supplementation of MDSCs in murine and human lymphoma culture augments early expression of MDR phenotypes than culture without MDSCs, correlated well with in-vitro drug efflux and tumor progression. We found that MDSC secreted cytokines IL-6, IL-10, IL-1β are the dominant factors elevating MDR expression in cancer cells, neutralization of MDSC secreted IL-6, IL-10, IL-1β reversed the MDR trait. Moreover, we identified MDSC secreted IL-6/IL-10/IL-1β induced STAT1/STAT3/NF-κβ signaling axis as a targeted cascade to promote early drug resistance in cancer cells.ConclusionOur data suggests that screening patients for high titre of M-MDSCs might be considered as a new potential biomarker and treatment modality in overcoming chemo-resistance in NHL patients

Dopamine Regulates Angiogenesis in Normal Dermal Wound Tissues

Cutaneous wound healing is a normal physiological process and comprises different phases. Among these phases, angiogenesis or new blood vessel formation in wound tissue plays an important role. Skin is richly supplied by sympathetic nerves and evidences indicate the significant role of the sympathetic nervous system in cutaneous wound healing. Dopamine (DA) is an important catecholamine neurotransmitter released by the sympathetic nerve endings and recent studies have demonstrated the potent anti-angiogenic action of DA, which is mediated through its D2 DA receptors. We therefore postulate that this endogenous catecholamine neurotransmitter may have a role in the neovascularization of dermal wound tissues and subsequently in the process of wound healing. In the present study, the therapeutic efficacy of D2 DA receptor antagonist has been investigated for faster wound healing in a murine model of full thickness dermal wound. Our results indicate that treatment with specific D2 DA receptor antagonist significantly expedites the process of full thickness normal dermal wound healing in mice by inducing angiogenesis in wound tissues. The underlined mechanisms have been attributed to the up-regulation of homeobox transcription factor HoxD3 and its target α5β1 integrin, which play a pivotal role in wound angiogenesis. Since D2 DA receptor antagonists are already in clinical use for other disorders, these results have significant translational value from the bench to the bedside for efficient wound management along with other conventional treatment modalities

Dopamine Regulates Mobilization of Mesenchymal Stem Cells during Wound Angiogenesis

Angiogenesis is an important step in the complex biological and molecular events leading to successful healing of dermal wounds. Among the different cellular effectors of wound angiogenesis, the role of mesenchymal stem cells (MSCs) is of current interest due to their transdifferentiation and proangiogenic potentials. Skin is richly innervated by sympathetic nerves which secrete dopamine (DA) and we have recently shown that concentration of DA present in synaptic cleft can significantly inhibit wound tissue neovascularization. As recent reports indicate that MSCs by mobilizing into wound bed play an important role in promoting wound angiogenesis, we therefore investigated the effect of DA on the migration of MSCs in wound tissues. DA acted through its D2 receptors present in the MSCs to inhibit their mobilization to the wound beds by suppressing Akt phosphorylation and actin polymerization. In contrast, this inhibitory effect of DA was reversed after treatment with specific DA D2 receptor antagonist. Increased mobilization of MSCs was demonstrated in the wound site following blockade of DA D2 receptor mediated actions, and this in turn was associated with significantly more angiogenesis in wound tissues. This study is of translational value and indicates use of DA D2 receptor antagonists to stimulate mobilization of these stem cells for faster regeneration of damaged tissues

Melioidosis of the Head and Neck: A Case Series from Eastern India

Melioidosis is an emerging entity in India. Though it is a potentially fatal disease, prognosis is excellent with early detection and appropriate management, especially of localized infections like abscesses of the head and neck area. We report nine cases of focal abscesses in the head and neck region due to Burkholderia pseudomallei, the causative agent of melioidosis, presenting to our hospital within a span of two-and-half years. Since melioidotic abscesses in the cervicofacial and head and neck region are likely to be confused with cold abscesses caused by Mycobacterium tuberculosis in a tuberculosis-endemic country like India, increased vigilance is necessary because of the widely divergent treatment modalities of the two disease entities