Detrital zircon data have recently become available from many different portions of the Tibetan–Himalayan orogen. This study uses 13,441 new or existing U‐Pb ages of zircon crystals from strata in the Lesser Himalayan, Greater Himalayan, and Tethyan sequences in the Himalaya, the Lhasa, Qiangtang, and Nan Shan–Qilian Shan–Altun Shan terranes in Tibet, and platformal strata of the Tarim craton to constrain changes in provenance through time. These constraints provide information about the paleogeographic and tectonic evolution of the Tibet–Himalaya region during Neoproterozoic to Mesozoic time. First‐order conclusions are as follows: (1) Most ages from these crustal fragments are <1.4 Ga, which suggests formation in accretionary orogens involving little pre‐mid‐Proterozoic cratonal material; (2) all fragments south of the Jinsa suture evolved along the northern margin of India as part of a circum‐Gondwana convergent margin system; (3) these Gondwana‐margin assemblages were blanketed by glaciogenic sediment during Carboniferous–Permian time; (4) terranes north of the Jinsa suture formed along the southern margin of the Tarim–North China craton; (5) the northern (Tarim–North China) terranes and Gondwana‐margin assemblages may have been juxtaposed during mid‐Paleozoic time, followed by rifting that formed the Paleo‐Tethys and Meso‐Tethys ocean basins; (6) the abundance of Permian–Triassic arc‐derived detritus in the Lhasa and Qiangtang terranes is interpreted to record their northward migration across the Paleo‐ and Meso‐Tethys ocean basins; and (7) the arrival of India juxtaposed the Tethyan assemblage on its northern margin against the Lhasa terrane, and is the latest in a long history of collisional tectonism.
Abstract Type 1 diabetes (T1D) is considered to be a T cell driven autoimmune disease, for which clinical treatment of T1D has been unsuccessful creating a need for immunotherapeutics to match world-wide rising incidence of disease. Pancreatic inflammation in non-obese diabetic (NOD) mice is primarily T cell mediated resulting in immune destruction of the insulin producing β cells in the pancreatic islets of Langerhans, which induces a hyperglycemic state that requires daily insulin injections to maintain homeostasis. The use of nondepleting antibodies provides a strategy to modulate the function of T cells while avoiding their systemic depletion. Our lab has previously reported that treatment of recent onset diabetic NOD mice with a short-course of both monoclonal anti-CD4 and anti-CD8 (anti-CD4/CD8) antibodies rapidly and indefinitely reversed established T1D. Remission of T1D by anti-CD4/CD8 treatment is accompanied by the egress of T cells from the pancreatic islets and pancreatic draining lymph node. Microarray analysis of anti-CD4/CD8 treated T cells revealed increased activity of the Forkhead box protein O1 (Foxo1) transcriptional axis that controls expression of the blood homing chemokine receptor sphingosine-1-phosphate receptor 1 (S1Pr1). In contrast, T cell activation related genes that promote tissue residency of T cells were down regulated. T cell receptor (TCR) signaling negatively regulates Foxo1 transcriptional activity by phosphorylation via the AKT signaling pathway. Our studies have revealed that dampened TCR signaling shortly after anti-CD4/CD8 treatment results in enhanced Foxo1 transcriptional activity promoting S1Pr1-mediated T cell egress from inflamed tissues providing long-term protection from T1D.
We have shown previously that pre-exposure of neutrophils to TNF significantly enhanced their killing of opsonized Staphylococcus aureus. We now demonstrate that the ability of TNF to enhance the bactericidal activity is dependent on preincubation time; enhancement was still evident when TNF and bacteria were added simultaneously to neutrophils but if TNF addition was delayed by 5 min, no enhancement was seen. Evidence is presented that suggests that this could be related to a down-regulation of TNF receptors by the bacteria, but in addition, the release of TNF receptor fragments may contribute to the inhibition observed. Scatchard analyses demonstrated a decrease from approximately 3000 TNF receptor (receptor binding) sites per cell to 450 following treatment with S. aureus, but essentially no change in receptor affinity. Using mAb directed against the type A (75 kDa) receptor (utr-1) and the type B (55 kDa) receptor (htr-9), it was found that the expression of both receptors was decreased following treatment with the bacteria. The time course of loss of these receptors showed that the surface expression of both molecules was markedly decreased by 5 min which correlated with the loss in ability of TNF to enhance the bactericidal activity. In contrast to changes seen in the binding of TNF, similarly treated neutrophils showed essentially no change in the binding of radiolabeled tripeptide FMLP and, if anything, an increase in the expression of the CD11b Ag (CR3 receptor). When another phagocytic stimulus was used, opsonized fungi (Torulopsis glabrata), a similar depression of TNF binding was also found, but opsonized sheep erythrocytes had no effect on the TNF binding, suggesting that the effects on the TNF receptor cannot be explained simply on the basis of particle phagocytosis.
We investigate the role of landslide dams, spatial changes in lithology, and rock uplift on faults in the formation of knickzones on bedrock rivers. We focus our analysis in the southwestern Annapurna Range of the central Nepalese Himalaya where detailed geologic maps, topographic data, field observations, and aerial photographs are available. We identified knickzones in our study area from normalized river steepness indices (k sn values) extracted from river longitudinal profiles derived from a 25 m digital elevation model we interpolated from digitized topographic map contours. We compared the location of these knickzones with (1) lithologic contacts and faults from a detailed geologic map of the Modi Khola valley and (2) inferred ancient landslide dam features mapped from field observations and aerial photographs. The steepest location on the Modi Khola occurs near the same latitude as the steepest reach on the Mardi Khola located directly to the east, potentially highlighting a major topographic transition across the Annapurna. However, we find that landslide dams once blocked the flow of the Modi Khola, and damming followed by incision after landslide breaching can explain the location of these knickzones without the need for active faulting near the Main Central thrust. We also conclude that (1) knickzones do not correlate with any spatial changes in lithology and (2) knickzones generated by rock uplift on unmapped faults cannot be ruled out. We emphasize that disentangling the processes responsible for knickzone formation remains challenging even when high‐resolution geologic and topographic data are available.
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