Fold and thrust belts (FTBs) accommodate tectonic convergence through folding and faulting of crustal rocks during a collisional event between two continental plates. Although evidence of distributed ...deformation is common in FTBs that usually leads to continuous foliations and regionally occurring ductile structures of multiple orders, it has rarely been given much attention assuming that zones of localized deformation, like shear zones and brittle faults, accommodate the entire amount of tectonic convergence. This study presents 3D laboratory-scale models, using viscous thin sheet as crustal layers, to understand the evolution of ductile strain in a tectonic wedge. We varied the degree of mechanical coupling at the basal decollement (i.e., weak versus strong) to investigate this issue at constant convergence velocity in all experiments to avoid the influence of rate-dependence on viscous rheology. Our results reveal that the strength of basal decollement controls the mode of wedge growth and hence, the strain pattern particularly towards the hinterland. The weak decollement models yield a zone of constriction towards the central part of hinterland, explaining the occurrence of isolated patches of L-tectonites and cross-folds in FTBs; while the strong decollement condition allows gravity driven flow to be active in the hinterland, leading to orogen-parallel recumbent folds. In contrast, both weak and strong decollement models produce deformation that characterises the commonness of pervasive, hinterland dipping ductile fabrics towards the mountain front. We correlate our findings to show that spatio-temporal variations in basal coupling are responsible for varying occurrence of ductile structures in FTBs.
•Development of ductile structures in fold-and-thrust belts is sensitive to decollement strength.•L-tectonites and cross folds preferentially localize in a tectonic wedge over weak decollement.•Strong decollement leads to recumbent fold in convergent setting.•Hinterland-dipping ductile fabrics in the foreland correspond to flattening type of deformation.
Oncolytic virotherapy for cancer treatment utilizes viruses for selective infection and death of cancer cells without any adverse effect on normal cells. We previously reported that the human ...respiratory syncytial virus (RSV) is a novel oncolytic virus against androgen-independent PC-3 human prostate cancer cells. The present study extends the result to androgen-dependent prostate cancer, and explores the underlying mechanism that triggers RSV-induced oncolysis of prostate cancer cells.
The oncolytic effect of RSV on androgen-sensitive LNCaP human prostate cancer cells and on androgen-independent RM1 murine prostate cancer cells was studied in vitro in culture and in vivo in a xenograft or allograft tumor model. In vitro, cell viability, infectivity and apoptosis were monitored by MTT assay, viral plaque assay and annexin V staining, respectively. In vivo studies involved virus administration to prostate tumors grown in immune compromised nude mice and in syngeneic immune competent C57BL/6J mice. Anti-tumorogenic oncolytic activity was monitored by measuring tumor volume, imaging bioluminescent tumors in live animals and performing histopathological analysis and TUNEL assay with tumors
We show that RSV imposes a potent oncolytic effect on LNCaP prostate cancer cells. RSV infectivity was markedly higher in LNCaP cells compared to the non-tumorigenic RWPE-1 human prostate cells. The enhanced viral burden led to LNCaP cell apoptosis and growth inhibition of LNCaP xenograft tumors in nude mice. A functional host immune response did not interfere with RSV-induced oncolysis, since growth of xenograft tumors in syngeneic C57BL/6J mice from murine RM1 cells was inhibited upon RSV administration. LNCaP cells failed to activate the type-I interferon (IFNα/β)-induced transcription factor STAT-1, which is required for antiviral gene expression, although these cells could produce IFN in response to RSV infection. The essential role of IFN in restricting infection was further borne out by our finding that neutralizing IFN activity resulted in enhanced RSV infection in non-tumorigenic RWPE-1 prostate cells.
We demonstrated that RSV is potentially a useful therapeutic tool in the treatment of androgen-sensitive and androgen-independent prostate cancer. Moreover, impaired IFN-mediated antiviral response is the likely cause of higher viral burden and resulting oncolysis of androgen-sensitive prostate cancer cells.
This study recognizes a transition in the modes of ductile deformation across the Himalayan Crystalline Complex (HCC) from field and microstructural evidence. This transition leads to the Main ...Central Thrust (MCT) zone localization in the Darjeeling-Sikkim Himalaya. In the initial stage of crustal shortening (prior to ∼16 Ma), the HCC experienced temporally varying distributed ductile strains that produced regionally occurring planar fabrics and folds of three generations. Thereafter, the tectonic transition (from distributed to localized deformation) at ∼16 Ma occurred, forming the MCT zone in the HCC. This MCT zone (∼4–6 km thick) marks a diffuse metamorphic/rheological boundary between the hot HCC and the relatively colder Lesser Himalayan terrane to the south. The field data suggests that the base of compressed reverse paleo-isograds at the bottom of the MCT zone coincides with the transition of quartz creep mechanisms, from sub-grain rotation (SGR) to grain boundary migration (GBM). The present study documents the prograde metamorphic imprints to establish the P-T conditions of these multiple deformation episodes. Finally, this study presents a conceptual tectonic model, based on previous laboratory findings, to propose a two-stage tectono-thermal evolution of the Higher Himalaya.
•High-grade Himalayan Crystalline rocks record stages of crustal thickening•Viscous wedge model explains the spatial variations in the complex fold interference pattern in Darjeeling-Sikkim Himalaya•Main Central Thrust (MCT) zone represents a rheological and metamorphic boundary
NF-κB is known to exert its antiviral innate immune response via the IFN-β-induced Janus kinase/signal transducers and activators of transcription pathway. However, our current studies have ...demonstrated that activated NF-κB is capable of directly establishing an antiviral state independent of IFN or secreted soluble factor(s) against two highly pathogenic respiratory RNA viruses. Human parainfluenza virus type 3, a mildly cytopathic virus that induced NF-κB very early during infection was converted to a virulent virus after NF-κB inhibition. In contrast, a highly cytopathic virus, human respiratory syncytial virus that induced NF-κB late during infection, was converted to a mildly cytopathic virus after NF-κB induction before virus replication. This interconversion of cytopathic phenotypes of viruses after NF-κB modulation was further shown to be independent of IFN and soluble secreted factors(s). Moreover, tumor necrosis factor α (TNF-α) and IL-1β elicited an antiviral response, which was NF-κB-dependent. Thus, NF-κB induction directly confers an essential innate antiviral response against human parainfluenza virus type 3 and respiratory syncytial virus, which is independent of IFN-inducible factor(s).
Cells that are metabolically active and in a high degree of differentiation and proliferation require cobalamin (Cbl: vitamin
B 12 ) and they obtain it from the circulation bound to transcobalamin ...(TC) via the transcobalamin receptor (TC-R). This study
has investigated the plasma membrane dynamics of TC-R expression in polarized human intestinal epithelial Caco-2 cells using
techniques of pulse-chase labelling, domain-specific biotinylation and cell fractionation. Endogenously synthesized TC-R turned
over with a half-life ( T 1/2 ) of 8 h following its delivery to the basolateral plasma membrane (BLM). The T 1/2 of BLM delivery was 15 min and TC-R delivered to the BLM was endocytosed and subsequently degraded by leupeptin-sensitive
proteases. However, about 15% of TC-R endocytosed from the BLM was transcytosed ( T 1/2 , 45 min) to the apical membranes (BBM) where it underwent endocytosis and was degraded. TC-R delivery to both BLM and BBM
was inhibited by Brefeldin A and tunicamycin, but not by wortmannin or leupeptin. Colchicine inhibited TC-R delivery to BBM,
but not BLM. At steady state, apical TC-R was associated with megalin and both these proteins were enriched in an intracellular
compartment which also contained Rab5 and transferrin receptor. These results indicate that following rapid delivery to both
plasma membrane domains of Caco-2 cells, TC-R undergoes constitutive endocytosis and degradation by leupeptin-sensitive proteases.
TC-R expressed in apical BBM complexes with megalin during its transcytosis from the BLM.
The mid-crustal ramp on the Main Himalayan Thrust (MHT) in the Lesser Himalaya Sequence (LHS) is the most critical geometrical asperity to trigger major seismic events in the Himalaya, including the ...2015 Mw 7.8 Gorkha, Nepal earthquake. However, it is still not well understood what caused the MHT to ramp up at laterally varying locations in central to eastern Himalaya during the southward propagation of the Himalayan tectonic wedge. Based on laboratory and numerical model experiments, approximated to the central (Nepal) and eastern (Bhutan) Himalayan geological settings, we show that the coal-bearing Gondwana horizon in the stratigraphic sequence has played a crucial role in producing the mid-crustal ramp on the MHT. During the southward propagation of the Himalayan wedge, the mechanically weak Gondwana sequence resulted in strain localization at its northern edge, and it eventually caused the MHT to ramp from a depth of >20 km to ~6–7 km. Combining our experimental and field observations with the geophysical sections, we interpret that a strike-wise non-uniform occurrence of the Gondwana horizon is responsible for the MHT to ramp at different locations, separated by N-S trending natural barriers, like tear faults. The weak-zone model also explains the rock uplift versus erosion pattern recorded in central Nepal. The ramp-induced surface uplift rates, calculated from our model, are in good agreement with those reported from central Nepal (U* ~ 0.28, normalized to the convergent rate).
•Mechanically weak stratigraphic horizon acts as a distinct unit to localize mid-crustal ramp on the Main Himalayan Thrust•Segmented MHT ramp always marks the northernmost extension of the Gondwana basin in eastern Himalaya•Mid-crustal ramping gives way to focused crustal uplift in the Lesser Himalaya•Absence of Gondwana horizon in the western Bhutan is the key for missing mid-crustal ramp and seismically quiescent state
The Tripura Mizoram fold belt (TMFB) belongs to the widest segment of the outer wedge of Indo-Burma Wedge (IBW). The structure of the outer wedge is characterized by a series of north-south trending ...anticlines-and-synclines of varying tightness, which progressively decreases towards the foreland direction. To explain their development, earlier workers proposed the model of fault-related folding, assuming that crustal shortening between India and Burma occurred dominantly by brittle deformation. However, our field investigations in TMFB reveal imprints of unequivocal ductile deformation, including interference of folds. Based on new structural map coupled with outcrop-scale structures, we recognize the existence of multi-ordered folds in the Neogene sequence of TMFB. However, the complexity of folding increases toward the hinterland part of wedge. We substantiate the spatial variations of penetrative ductile structures of TMFB with laboratory experiments under oblique convergence. Model results show consistency with the existence of along-strike variations of deformation intensity in the outer wedge of IBW, which gradually increases southward with narrowing the width of the wedge. Combining our field observations and laboratory experiments with earthquake focal depth distributions around TMFB, we propose that stratigraphic horizons of the entire outer wedge are mechanically weak to have deformed dominantly by brittle faulting.
•The outer wedge of IBW accommodates crustal shortening by buckle folding.•The weak Neogene sediments of the outer wedge material forces the decollement to localize at a shallow crustal depth.•Variations in fold style from foreland to hinterland in TMFB is consistent with viscous wedge model.
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