Cytoskeletal Regulation and Morphogen Signaling During Synaptic Outgrowth at the \u3cem\u3eDrosophila\u3c/em\u3e Larval Neuromuscular Junction : A Dissertation

Synaptic plasticity, in its broadest sense, can be defined as the ability of synapses to be modified structurally and functionally in response to various internal and external factors. Growing evidence has established that at the very core of these modifications are alterations in the cytoskeletal architecture. This discovery has led to the unearthing of a number of signaling pathways that might be involved in cytoskeletal regulation and also in the regulation of other aspects of synapse development and plasticity. In this regard, polarity proteins and secreted morphogens such as the Wnt proteins, typically involved in embryonic development, are emerging as critical determinants of synaptic growth and plasticity. However, their mechanism of action at synapses needs further investigation. Additionally, not much is known about how these morphogens are secreted or transported across synapses. Using the Drosophila larval NMJ as a model system, I have addressed aspects related to the issues mentioned above in the subsequent body of work. In the first half of my thesis, I have uncovered a role for the aPKC/Baz/Par-6 polarity protein complex in the regulation of the postsynaptic actin cytoskeleton in conjunction with the lipid and protein phosphatase PTEN. In the second half of my thesis, I have contributed to the elucidation of mechanisms underlying the secretion of Wg, the Drosophila Wnt homolog. Our findings suggest that Wnts might be secreted via a previously unidentified mechanism involving the release of exosome like vesicles from the presynapse and this process requires Evi/Wntless (Evi), a protein dedicated to Wnt secretion. Alterations in signaling pathways and aberrant cytoskeletal regulation lead to a variety of neurological disorders. The body of work in this thesis will provide a deeper understanding of the mechanisms involved in synaptic plasticity and provide a basis for uncovering similar pathways in the context of vertebrate synapses

Gamma-Delta T-cell Lymphoma: An Overview

Gamma-delta T-cell lymphomas are very rare and aggressive T-cell neoplasms with complex heterogenicity and diagnostic complexity. Gamma-delta T lymphocytes originate from CD4− CD8− (double negative) thymocytes in the bone marrow and are distinct from alpha beta subtype. Four entities of gamma-delta lymphomas recognized by 2016 WHO classification of lymphoid neoplasms include: hepatosplenic Tγδ lymphoma (HSγδTL), primary cutaneous gamma-delta TCL (PCTCL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) and large granular lymphocytic leukemias (T-LGL). Extensive literature search based on small case series and case reports identifies few more subtypes of gamma-delta T-lymphomas which were not previously classified by World Health Organization. There remains a critical gap in our understanding of the subtypes of gamma-delta T-cell lymphomas and a lack of updated summarization. In this review, we summarize in detail on the classification, biology, heterogenicity, diagnosis, clinical behavior and treatment options of these rare but clinically important entities

Studies on development and storage stability of dehydrated pumpkin based instant soup mix

The study was carried out to develop and standardize Instant Soup Mix (ISM) from dehydrated pumpkin powder and to evaluate nutritional (moisture, sugars, protein, ?-carotene, fat, fibre and water activity) and sensory qualities (colour, texture, flavour and overall acceptability) for determining its shelf-life during a period of six month. It was packed in aluminium laminated pouches and was analyzed periodically for changes in quality. Among various recipes optimized for the development of soup mix, soup mix containing 20g pumpkin powder, 5g moong dhal, 15g tomato powder, 11.4g spices (salt and black pepper) and condiments (onion, garlic and ginger powder), 2g dried pea, 2g dried spinach, and 2g dried carrot was selected as base recipe for addition of different starch source viz. rice, corn and potato @ 10 g. From the nutritional analysis, it was observed that corn based Instant Soup Mix had higher ?-carotene (7.01 mg/100 g) and protein (12.65 %) content, while fibre (2.09 %) was higher in soup mix containing rice starch. It was observed that on the basis of sensory evaluation corn based soup mix was more acceptable. Therefore, results of nutrition and sensory evaluation indicated that a good quality ISM can be prepared by using corn starch. During the six month of storage, there was about 5.49 per cent increase in moisture, 3.16 and 5.27 per cent decrease in protein and ?-carotene, respectively, along with slight losses in total sugars, fat and sensory quality. Further, the product was stable for 6 months under ambient condition

Sarcoid-Like Reaction Associated with Renal Cell Carcinoma - A Case Report.

Renal cell carcinoma (RCC) is a highly vascular tumor, which may spread to the lungs and other organs. It often presents with localized or systemic manifestation, including paraneoplastic syndromes. Sarcoidosis is a systemic granulomatous inflammatory disease characterized by non-caseating granulomas that typically afflicts the respiratory system. In the absence of any evidence of systemic sarcoidosis they are referred to as sarcoid-like reactions. Non-caseating epithelioid granulomas, also regarded to sarcoid-like granulomas have been described in association with certain malignancies such as carcinomas of the breast, colon, seminoma, and Hodgkin\u27s lymphoma. However, sarcoid like reaction associated with renal cell carcinoma is uncommon. Herein we present a rare case of a patient with renal cell carcinoma with mediastinal lymphadenopathy initially thought to metastatic disease, though revealed a sarcoid-like reaction with review of literature

Paraneoplastic Pemphigus: An Indication for Treatment in Chronic Lymphocytic Leukemia

Paraneoplastic disorders are rare multiorgan diseases associated with hematological malignancies such as chronic lymphocytic leukemia (CLL). Some of these paraneoplasms manifest as cutaneous lesions, appearing as a simple rash, ulcers or skin thickening. The pathogenesis for this process has been described as development of certain autoimmune reactions against cell wall antigens and proteins. An example is paraneoplastic pemphigus (PNP) which manifests as cutaneous bullae. Bullae may occur anytime during the course of the malignancy i.e. acute phase or remission. Diagnosis involves evaluation of clinical findings, serology and presence of characteristic histological findings. Its pathogenesis is described as development of auto-antibodies against cell junctional and basement membrane proteins. Presence of paraneoplasms has been associated with poorer prognosis and increased mortality in hematological malignancies including CLL. Currently, there are established indications for the treatment of CLL; however, presence of paraneoplasms as an indication for treatment is unclear. Patients with paraneoplasms who underwent expeditious treatment have exhibited better clinical outcomes. Herein we describe a case of a CLL patient in remission presenting with PNP and its response to treatment

Cholangiocarcinoma Presenting as Humoral Hypercalcemia of Malignancy: A Case Report and Literature Review

Humoral hypercalcemia of malignancy (HHM) is most commonly encountered in squamous cell carcinoma (SCC) of different organs, and It is characterized by elevated parathyroid hormone-related peptide (PTHrP) levels. It may be seen as a manifestation of cholangiocarcinoma (CCC) at presentation and later in the course of the disease. However, HHM due to intrahepatic cholangiocarcinoma is a rare association and is associated with a poor prognosis. We herein report a case of hypercalcemia presenting as the first manifestation of an underlying rare variant of intrahepatic cholangiocarcinoma. Our patient is a 57-year-old male who presented to the emergency room with severe symptoms of constipation and polyuria and was admitted to the hospital for symptomatic hypercalcemia. He was found to have a hypermetabolic 15 cm liver mass, abdominal lymph nodes on imaging, which was subsequently diagnosed as adenosquamous cholangiocarcinoma by liver biopsy. This necessitated an urgent inpatient treatment with gemcitabine/cisplatin combination chemotherapy to control the aggressive nature of the malignancy. However, he deteriorated and expired after three months of his diagnosis. Adenosquamous cholangiocarcinoma is a very rare variant of a liver tumor. It develops due to squamous metaplasia of an underlying cholangiocarcinoma and usually has aggressive clinicopathological features. HMM is a life-threatening, yet unrecognized, phenomenon of cholangiocarcinoma, which represents a poor prognostic marker. Prompt recognition of this complication is important for preventing serious complications associated with hypercalcemia and to improve the quality of life of these patients

Comparative study on physical characteristics and nutritional composition of pumpkin (Cucurbita moschata) at different stages of maturity

Present day scientists are paying more attention towards developing new value-added products from underutilized crops for economic growth in agriculture system. Therefore, present experiment was undertaken to explicate the nutritional potential of pumpkin (Cucurbita moschata) at different stage of maturity until it is fully mature and ripe. Variation in different physico-biochemical properties,for example moisture content, sugars, titratable acidity (TA), crude proteins, crude fat, β-carotene, ascorbic acid, pectin and fibre in flesh, peel and seeds of fruit provides the better understanding for its utilization in preparation of various products. The firmness of pumpkin increased from 4.94 lbs/inch2 at 15 DAA (Days after antesis) to 22.50 lbs/inch2 at ripe stage during maturity. β-carotene content of flesh increased from 1.34 to13.30 mg/100g and 26.26 while quantity ascorbic acid in flesh of fruit declined from 26.46 to 13.16 mg/100 g at 15 DAA to ripe stage.In seeds crude fat increased from 5.43 to 50.24% and protein increase was found to be from 4.10 to 19.56%. Pectin content (as calcium pectate) of flesh and peel increased from 0.56 to 1.89 and 0.78 to 2.15%, respectively from 15 DAA to 45 DAA and at later stage it decreased. The knowledge about physic-chemical quality of pumpkin at different stage of maturity would help in selecting right stage of fruit maturity for its utilization in acceptable manner

Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Preparation of late Drosophila embryonic fillets

Beyond the age of ~15 h (at 25 degrees C), Drosophila embryos become impenetrable to aqueous fixatives and staining methods as a result of cuticle deposition. This problem can be overcome using flat or fillet preparations, as described in this protocol