Role of granulosa cell mitogen-activated protein kinase 3/1 in gonadotropin-mediated meiotic resumption from diplotene arrest of mammalian oocytes

In mammals, preovulatory oocytes are encircled by several layers of granulosa cells (GCs) in follicular microenvironment. These follicular oocytes are arrested at diplotene arrest due to high level of cyclic nucleotides from encircling GCs. Pituitary gonadotropin acts at the level of encircling GCs and increases adenosine 3′,5′-cyclic monophosphate (cAMP) and guanosine 3′,5′-cyclic monophosphate (cGMP) and activates mitogen-activated protein kinase 3/1 (MAPK3/1) signaling pathway. The MAPK3/1 disrupts the gap junctions between encircling GCs and oocyte. The disruption of gap junctions interrupts the transfer of cyclic nucleotides to the oocyte that results a drop in intraoocyte cAMP level. A transient decrease in oocyte cAMP level triggers maturation promoting factor (MPF) destabilization. The destabilized MPF finally triggers meiotic resumption from diplotene arrest in follicular oocyte. Thus, MAPK3/1 from GCs origin plays important role in gonadotropin-mediated meiotic resumption from diplotene arrest in follicular oocyte of mammals.     

Knockdown of PINCH-1 protein sensitizes the estrogen positive breast cancer cells to chemotherapy induced apoptosis

Introduction

PINCH-1 is a ubiquitously expressed protein belonging to the focal adhesion protein group which has a role in cell survival, spreading, adhesion and migration. It has been implicated in pathogenesis of several cancers. In the present study we aimed to investigate the role of this protein in estrogen positive and negative breast cancer subtypes.

Hypereosinophilia in Acute Lymphoblastic Leukemia: Two Cases with Review of Literature

Eosinophilia is rare in acute leukemia at presentation. Discrete reports and case studies in recent years have created significant interest in the field of “Acute leukemia with eosinophilia”. We herein present two cases of eosinophilia in association with acute lymphoblastic leukemia with brief review of literature in this field. First case is about 21-year-old female who presented with mediastinal mass along with leukocytosis and hypereosinophilia. On evaluation, she was found to have T cell acute lymphoblastic leukemia. After ruling out benign causes of eosinophilia, she was treated with modified BFM-90 protocol. Her eosinophilia resolved after 4 weeks of induction therapy. Second case is about 32-year-old male who was diagnosed as a case of mixed phenotype leukemia (B cell/myeloid type) along with severe eosinophilia. His hypereosinophilia finally resolved by week 16 of modified BFM-90 protocol. Diagnosing ALL is challenging when eosinophilia is the initial presentation. These two cases emphasize on the importance of considering ALL amongst one of the etiological causes of eosinophilia as delay in diagnosis endangers patient’s life at risk. Also eosinophilia per se is an independent poor risk factor, hence prompt diagnosis and early treatment is the key in all such cases.     

Myeloid Sarcoma: An Unusual Case of Mediastinal Mass and Malignant Pleural Effusion with Review of Literature

Myeloid sarcoma is an extramedullary tumor seen most commonly in patients with acute myeloid leukemia and less frequently in chronic myeloid leukemia, myelodysplastic syndrome and rarely, in an isolated form without any other underlying malignancy. Malignant pleural effusion in hematological malignancies is rare when compared with solid tumors. We present an unusual case of myeloid sarcoma in which a mediastinal mass with pleural effusion was the initial presentation. A 27 year old gentleman presented with complaints of fever, chest pain and swelling in the anterior chest wall for 6 months. Examination revealed a lump measuring 5 × 5 cm on the left side of the chest wall. Hematological evaluation showed hemoglobin-14.2 g/dL, platelet count-233 × 10⁹/L, TLC-117 × 10⁶/L with normal differential counts. Contrast enhanced computerised tomography (CECT) confirmed the presence of a soft tissue mass in the superior mediastinum abutting against the chest wall. Core biopsy was suggestive of myeloid sarcoma and immunohistochemistry was positive for myeloperoxidase and negative for CD3, CD 20 and CD 23. Pleural fluid analysis showed the presence of malignant cells. Bone marrow examination did not show an excess of blasts. A final diagnosis of extramedullary myeloid sarcoma with malignant pleural effusion was made. The patient was given induction chemotherapy (3 + 7 regimen) with daunorubicin and cytosine arabinoside. Repeat CECT done on day 28 showed complete resolution of pleural effusion and significant reduction in the size of mediastinal mass. The patient has successfully completed three cycles of consolidation therapy following which there has been complete resolution of the mass. He remains asymptomatic on close follow up.     

Erosion in southern Tibet shut down at ～10 Ma due to enhanced rock uplift within the Himalaya

Exhumation of the southern Tibetan plateau margin reflects interplay between surface and lithospheric dynamics within the Himalaya–Tibet orogen. We report thermochronometric data from a 1.2-km elevation transect within granitoids of the eastern Lhasa terrane, southern Tibet, which indicate rapid exhumation exceeding 1 km/Ma from 17–16 to 12–11 Ma followed by very slow exhumation to the present. We hypothesize that these changes in exhumation occurred in response to changes in the loci and rate of rock uplift and the resulting southward shift of the main topographic and drainage divides from within the Lhasa terrane to their current positions within the Himalaya. At ∼17 Ma, steep erosive drainage networks would have flowed across the Himalaya and greater amounts of moisture would have advected into the Lhasa terrane to drive large-scale erosional exhumation. As convergence thickened and widened the Himalaya, the orographic barrier to precipitation in southern Tibet terrane would have strengthened. Previously documented midcrustal duplexing around 10 Ma generated a zone of high rock uplift within the Himalaya. We use numerical simulations as a conceptual tool to highlight how a zone of high rock uplift could have defeated transverse drainage networks, resulting in substantial drainage reorganization. When combined with a strengthening orographic barrier to precipitation, this drainage reorganization would have driven the sharp reduction in exhumation rate we observe in southern Tibet.The Himalaya–Tibet orogenic system, formed by collision between India and Asia beginning ca. 50 Ma, is the most salient topographic feature on Earth and is considered the archetype for understanding continental collision. Geophysical and geologic research has illuminated the modern structure and dynamics of the orogen (1). Nonetheless, how the relatively low relief and high elevation Tibetan plateau grew spatially and temporally and what underlying mechanism(s) drove the patterns of plateau growth remain outstanding questions.In the internally drained central Tibetan plateau, evidence from carbonate stable isotopes suggest that high elevations persisted since at least 25–35 Ma (2, 3). Sustained high elevations since shortly after collision commenced have also been used to explain low long-term erosion rates in the internally drained plateau interior (4–6). In contrast to the central plateau, the externally drained Tibetan plateau margins serve as the headwaters for many major river systems in Asia. Because externally drained rivers provide an erosive mechanism to destroy uplifted terrane, understanding why these rivers have not incised further and more deeply into the Tibetan plateau is essential to decipher how the plateau grew. Recent research in the eastern (7, 8) and northern (9) Tibetan plateau indicates that erosion rates have increased significantly since ∼10 Ma. These increases suggest that rock uplift rates have also increased and that the plateau has expanded to the east and north during this time [due to lower crustal flow (7) or upper crustal extrusion (8) to the east and structural reorganization to the north (9)], causing rivers to steepen and erode at faster rates.The history of the southern Tibetan plateau margin, on the other hand, is less well understood. The southern Tibetan plateau is presently drained by the Yarlung and Indus Rivers, which each flow parallel to the Himalayan range for more than 1,000 km before descending from the plateau at the Himalayan syntaxes. Evidence from fossils and carbonate stable isotopes suggest that high elevations in the southern Tibetan plateau persisted since at least 15 Ma (10, 11) and potentially even before collision began (12). Additionally, sediments from the Himalayan foreland, Bengal, and Central Myanmar basins require external drainage of the southern Tibetan plateau since at least 14 Ma and potentially as early as 40 Ma (13–15). High elevations and external drainage since at least Middle Miocene time indicate that rock uplift rates in the southern Tibetan plateau may have kept up with the pace of river incision for tens of millions of years. However, cosmogenic nuclide concentrations indicate low erosion rates (typically <10² m/Ma) in both the Indus and Yarlung drainages over the last several hundred thousand years (16, 17). No data yet exist to test whether these slow erosion rates persisted over longer 10⁶- to 10⁷-y timescales. Therefore, it is uncertain how high elevations in the southern plateau have been sustained: are long-term rock uplift and erosion rates both high or have slow erosion rates persisted despite external drainage by some other mechanism?Here, we examine the exhumation history of the eastern part of the Tibetan plateau’s southern margin using thermochronometry, a technique in which thermal histories of rocks are constrained by the evolution of geochemical systems sensitive to temperatures within Earth’s upper crust. We present apatite ⁴He/³He, apatite and zircon (U-Th)/He, and biotite and K-feldspar ⁴⁰Ar/³⁹Ar thermochronometry data from granitic bedrock samples of the Cretaceous–Cenozoic Gangdese batholith in the eastern Lhasa terrane, southern Tibet. Samples were collected along a 1.2-km elevation transect near the eastern headwaters of the Lhasa River, a major tributary of the Yarlung River (Fig. 1 and SI Appendix, Table S1). This approach is advantageous for several reasons. First, by using a suite of thermochronometric systems sensitive to temperatures ranging from ∼30 °C to 350 °C, we can identify changes in exhumation rate over a longer duration than would be possible with any subset of them. Second, sampling along an elevation transect leverages the fact that rocks at different elevations within a pluton share a similar exhumation history but have different cooling histories. Resolvable differences in the cooling histories between rocks at different elevations can more tightly constrain the overall exhumation history than the cooling history of a single elevation sample. Third, to avoid the effects of local-scale tectonic exhumation, we collected samples in a location that is not in the footwall of one of the north-south trending rift systems in southern Tibet. Therefore, the data primarily record temporal trends in erosional exhumation of the region. With data from this sampling scheme, we use 3D thermokinematic models to constrain the timing of both large-scale unroofing of the Gangdese batholith and local, kilometer-scale relief development due to river incision. From these data and thermokinematic models, we develop a hypothesis for landscape evolution within the southern Tibetan plateau that we illustrate schematically using a simple numerical model.Open in a separate windowFig. 1.(A) Topography and (B) mean annual precipitation (MAP) in southern Tibet and the Himalaya. The yellow star marks the city of Lhasa and blue circles denote the sample locations. The following generalized geologic structures are also shown in A: GCT, Great Counter Thrust; GT, Gangdese Thrust; IYSZ, Indus-Yarlung Suture Zone; MBT, Main Boundary Thrust; MCT, Main Central Thrust; MFT, Main Frontal Thrust; STD, South Tibetan Detachment; WF, Woka fault. In B, major river networks draining the southern Tibetan plateau and Himalaya are shown in black, with the Yarlung River and the Lhasa River highlighted in white and tan, respectively. C shows a detailed view of our sample locations and the surrounding topography. Topography plotted from 90 m SRTM (Shuttle Radar Topography Mission) data; MAP plotted from TRMM (Tropical Rainfall Measurement Mission) 2B31 data collected between 1998 and 2009 (36); geologic structures based on Styron et al. (30), Decelles et al. (31), Yin et al. (33), and Hodges (44).     

Anti-arthritis activity of roots of Hemidesmus indicus R.Br. (Anantmul) in rats

ObjectiveTo investigate the protective effects of hydroalcoholic and its fractions from roots of Hemidesmus indicus on arthritis in in vitro models of rodents.MethodsPreliminary phytochemical analysis and thin-layer chromoatography were performed to analyze constituents of hydroalcoholic extract and its three fraction namely ethyl acetate fraction, chloroform fraction and residual fraction of root of Hemidesmus indicus. Arthritis rats models were established by Complete Freund's Adjuvant. The parameters including paw edema, body weight, arthritic index, erythrocyte sedimentation rate, serum rheumatoid factor, serum C-reactive protein, serum nitrite level, and histopathology of synovial joints were observed. Methotrexate was taken as positive control.ResultsRats treated with hydroalcoholic extract (450 mg/kg, p.o.), ethyl acetate (75 mg/kg, p.o.), chloroform (60 mg/kg, p.o) and residual fractions (270 mg/kg, p.o.), showed significant decrease in physical and biochemical parameters compared with arthritic model rats. Hydroalcoholic extract and its ethyl acetate fraction of Hemidesmus indicus showed significantly higher anti-arthritic activity than chloroform and residual fraction. Histopathological analysis demonstrated that both of hydroalcoholic extract and its ethyl acetate fraction had comparable anti-arthritic activity with methotrexates.ConclusionsThe present study suggests that Hemidesmus indicus has protective activity against arthritis and the activity might be attributed to presence of terpenoid in hydroalcoholic extract, as well as in ethyl acetate fraction.     

Coping strategies and learned helplessness of employed and nonemployed educated married women from India

In the present study, we compare three types of coping strategies (cognitive, physical, and social coping) and learned helplessness between married women who are either employed or nonemployed in Pune, India. A total of 100 employed women and 100 nonemployed women were surveyed. Employed women were found to have significantly higher cognitive, physical, and social coping, as well as lower learned helplessness than nonemployed women. Multiple roles of employed women and sense of control theories were used to explain the differences. We have found significant implications for the development of intervention programs for empowering women.