22 research outputs found
Indian Bengal Delta : climate change, awareness and responsibilities
The Bi-Monthly Newsletter âEqualnewsâ focuses on Environment and Systems of Inquiry. The topic is âIndian Bengal Delta: climate change, awareness and responsibilitiesâ (page 8-12). The Government of India has announced the National Climate Change Action Plan (2008) with eight National Missions, later to become twelve missions by 2014. The worldâs largest mangrove forests called âSundarbansâ (named after a species of mangrove Sundari /Hereteria) are part of the delta of Ganga-Brahmaputra-Meghna (GBM) basin, known also as the Indian Bengal Delta (IBD). The article reviews background and concerns of the IBD region, calling for good governance and co-ordinated action
Nitric oxide and hypoxia stimulate erythropoietin receptor via MAPK kinase in endothelial cells
Erythropoietin receptor (EPOR) expression level determines the extent of erythropoietin (EPO) response. Previously we showed that EPOR expression in endothelial cells is increased at low oxygen tension and that EPO stimulation of endothelial cells during hypoxia can increase endothelial nitric oxide (NO) synthase (eNOS) expression and activation as well as NO production. We now observe that while EPO can stimulate NO production, NO in turn can regulate EPOR expression. Human umbilical vein endothelial cells (HUVEC) treated with 10-50 pM of NO donor diethylenetriamine NONOate (DETANO) for 24 h showed significant induction of EPOR gene expression at 5% and 2% of oxygen. Also human bone marrow microvascular endothelial cell line (TrHBMEC) cultured at 21 and 2% oxygen with 50 uM DETANO demonstrated a time and oxygen dependent induction of EPOR mRNA expression after 24 and 48 h, particularly at low oxygen tension. EPOR protein was also induced by DETANO at 2% oxygen in TrHBMEC and HUVEC. The activation of signaling pathways by NO donor stimulation appeared to be distinct from EPO stimulation. In reporter gene assays, DETANO treatment of HeLa cells at 2% oxygen increased EPOR promoter activity indicated by a 48% increase in luciferase activity with a 2 kb EPOR promoter fragment and a 71% increase in activity with a minimal EPOR promoter fragment containing 0.2 kb 5'. We found that DETANO activated MAPK kinase in TrHBMEC both in normoxia and hypoxia, while MAPK kinase inhibition showed significant reduction of EPOR mRNA gene expression at low oxygen tension, suggesting MAPK involvement in NO mediated induction of EPOR Furthermore, DETANO stimulated Ala anti-apoptotic activity after 30 min in normoxia, whereas it inhibited Akt phosphorylation in hypoxia. In contrast, EPO did not significantly increase MAPK activity while EPO stimulated Akt phosphorylation in TrHBMEC in normoxia and hypoxia. These observations provide a new effect of NO on EPOR expression to enhance EPO response in endothelial cells, particularly at low oxygen tensions
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. Patientâs 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 Daltonâs 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-1ÎČ are the dominant factors elevating MDR expression in cancer cells, neutralization of MDSC secreted IL-6, IL-10, IL-1ÎČ reversed the MDR trait. Moreover, we identified MDSC secreted IL-6/IL-10/IL-1ÎČ induced STAT1/STAT3/NF-ÎșÎČ 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
Report of the Topical Group on Cosmic Probes of Dark Matter for Snowmass 2021
Cosmological and astrophysical observations currently provide the only
robust, positive evidence for dark matter. Cosmic probes of dark matter, which
seek to determine the fundamental properties of dark matter through
observations of the cosmos, have emerged as a promising means to reveal the
nature of dark matter. This report summarizes the current status and future
potential of cosmic probes to inform our understanding of the fundamental
nature of dark matter in the coming decade.Comment: Report of the CF3 Topical Group for Snowmass 2021; 35 pages, 10
figures, many references. V3 updates Fig 3-2 and the author lis
Dynamics of Hot QCD Matter -- Current Status and Developments
The discovery and characterization of hot and dense QCD matter, known as
Quark Gluon Plasma (QGP), remains the most international collaborative effort
and synergy between theorists and experimentalists in modern nuclear physics to
date. The experimentalists around the world not only collect an unprecedented
amount of data in heavy-ion collisions, at Relativistic Heavy Ion Collider
(RHIC), at Brookhaven National Laboratory (BNL) in New York, USA, and the Large
Hadron Collider (LHC), at CERN in Geneva, Switzerland but also analyze these
data to unravel the mystery of this new phase of matter that filled a few
microseconds old universe, just after the Big Bang. In the meantime,
advancements in theoretical works and computing capability extend our wisdom
about the hot-dense QCD matter and its dynamics through mathematical equations.
The exchange of ideas between experimentalists and theoreticians is crucial for
the progress of our knowledge. The motivation of this first conference named
"HOT QCD Matter 2022" is to bring the community together to have a discourse on
this topic. In this article, there are 36 sections discussing various topics in
the field of relativistic heavy-ion collisions and related phenomena that cover
a snapshot of the current experimental observations and theoretical progress.
This article begins with the theoretical overview of relativistic
spin-hydrodynamics in the presence of the external magnetic field, followed by
the Lattice QCD results on heavy quarks in QGP, and finally, it ends with an
overview of experiment results.Comment: Compilation of the contributions (148 pages) as presented in the `Hot
QCD Matter 2022 conference', held from May 12 to 14, 2022, jointly organized
by IIT Goa & Goa University, Goa, Indi
Shuchi Kapila. Educating Seeta: The Anglo-Indian Romance and the Poetics of Indirect Rule. Columbus: Ohio State University Press, 2010. ISBN: 978-0-8142-1126-7. Price: US$39.95
Trans-Status Subjects: Gender in the Globalization of South and Southeast Asia. Edited by Sonita Sarker Esha Niyogi De. Durham, N.C.: Duck University Press, 2002. xii, 344 pp. 21.95 (paper).
Thyroidal Regulation of Different Isoforms of NaKATPase in Glial Cells of Developing Rat Brain
The developmental profile of the different isoforms of NaKATPase have been investigated during
the first three weeks of postnatal development using primary cultures of isolated glial cells derived
from neonatal rat cerebra. Northern and Western blot analysis show that the expression of four isoforms
(
a
1
,
a
2
,
b
1
and
b
2
) in these cells increases progressively between 5 to 20 days of culture. Comparison
of the mRNA levels of these isoforms in thyroid hormone deficient (TH def) and thyroid hormone supplemented
(TH sup) cells cultured for 5 â 10 days, revealed for the first time that all four isoforms are
sensitive to T 3 in the glial cells. Furthermore immunocytochemical staining of these cells with isoform
specific NaKATPase antibodies also showed that the localization of the different isoforms in the TH
def cells were altered in comparison to that in the TH sup cells. These results establish glial cells as the
target cells for the regulation of NaKATPase by TH in the developing brain. © 2001 Elsevier Science
Inc. All rights reserved
Conjugated Bile Acids Promote Lymphangiogenesis by Modulation of the Reactive Oxygen Speciesâp90RSKâVascular Endothelial Growth Factor Receptor 3 Pathway
Conjugated bile acids (BA) are significantly elevated in several liver pathologies and in the metastatic lymph node (LN). However, the effects of BAs on pathological lymphangiogenesis remains unknown. The current study explores the effects of BAs on lymphangiogenesis. BA levels were elevated in the LN and serum of Mdr2â/â mice (model of sclerosing cholangitis) compared to control mice. Liver and LN tissue sections showed a clear expansion of the lymphatic network in Mdr2â/â mice, indicating activated lymphangiogenic pathways. Human lymphatic endothelial cells (LECs) expressed BA receptors and a direct treatment with conjugated BAs enhanced invasion, migration, and tube formation. BAs also altered the LEC metabolism and upregulated key metabolic genes. Further, BAs induced the production of reactive oxygen species (ROS), that in turn phosphorylated the redox-sensitive kinase p90RSK, an essential regulator of endothelial cell dysfunction and oxidative stress. Activated p90RSK increased the SUMOylation of the Prox1 transcription factor and enhanced VEGFR3 expression and 3-D LEC invasion. BA-induced ROS in the LECs, which led to increased levels of Yes-associated protein (YAP), a lymphangiogenesis regulator. The suppression of cellular YAP inhibited BA-induced VEGFR3 upregulation and lymphangiogenic mechanism. Overall, our data shows the expansion of the lymphatic network in presclerotic liver disease and establishes a novel mechanism whereby BAs promote lymphangiogenesis
The effect of amantadine on an ion channel protein from Chikungunya virus.
Viroporins like influenza A virus M2, hepatitis C virus p7, HIV-1 Vpu and picornavirus 2B associate with host membranes, and create hydrophilic corridors, which are critical for viral entry, replication and egress. The 6K proteins from alphaviruses are conjectured to be viroporins, essential during egress of progeny viruses from host membranes, although the analogue in Chikungunya Virus (CHIKV) remains relatively uncharacterized. Using a combination of electrophysiology, confocal and electron microscopy, and molecular dynamics simulations we show for the first time that CHIKV 6K is an ion channel forming protein that primarily associates with endoplasmic reticulum (ER) membranes. The ion channel activity of 6K can be inhibited by amantadine, an antiviral developed against the M2 protein of Influenza A virus; and CHIKV infection of cultured cells can be effectively inhibited in presence of this drug. Our study provides crucial mechanistic insights into the functionality of 6K during CHIKV-host interaction and suggests that 6K is a potential therapeutic drug target, with amantadine and its derivatives being strong candidates for further development