The proteostasis network and its decline in ageing

Ageing is a major risk factor for the development of many diseases, prominently including neurodegenerative disorders such as Alzheimer disease and Parkinson disease. A hallmark of many age-related diseases is the dysfunction in protein homeostasis (proteostasis), leading to the accumulation of protein aggregates. In healthy cells, a complex proteostasis network, comprising molecular chaperones and proteolytic machineries and their regulators, operates to ensure the maintenance of proteostasis. These factors coordinate protein synthesis with polypeptide folding, the conservation of protein conformation and protein degradation. However, sustaining proteome balance is a challenging task in the face of various external and endogenous stresses that accumulate during ageing. These stresses lead to the decline of proteostasis network capacity and proteome integrity. The resulting accumulation of misfolded and aggregated proteins affects, in particular, postmitotic cell types such as neurons, manifesting in disease. Recent analyses of proteome-wide changes that occur during ageing inform strategies to improve proteostasis. The possibilities of pharmacological augmentation of the capacity of proteostasis networks hold great promise for delaying the onset of age-related pathologies associated with proteome deterioration and for extending healthspan

Channel strategy: Formulation and adaptation

Inspired by open systems theories like the structural contingency theory (Lawrence and Lorsch 1967), population ecology theory (Hannan and Freeman 1977), and resource dependence theory (Pfeffer and Salancik 1978), several marketing scholars have investigated how channels adapt and organize themselves to cope with their environments. Curiously, however, the implication of such adaptive behaviour (i.e., the better adapted firms are more profitable) has not been investigated in the marketing literature. This paper aims to probe that question. Moreover, unlike previous marketing studies, we articulate the manufacturer's rather than the distributor's point-of-view, because channel strategy decisions are usually in the manufacturer's domain. We scrutinize firms' adaptive responses from a channel structure and channel task perspective. Results show that the better adapted firms deliver superior performance, and that the adaptive responses often occur subtly at the specific channel task level even when the channel structure itself may appear seemingly unaltered.structural contingency theory; population ecology theory; resource dependence theory;

Spectroscopic studies on the interaction of bilirubin with symmetrical alkyl diamines

The interactions of symmetrical alkyldiamines with bilirubin-IX α have been examined in dichloromethane and dioxane solutions, by visible region difference spectroscopy and florescence methods. In dioxane solutions a clear difference is observed between the complexes of the shorter chain diamines (number of spacer methylene groups (n ≤ 4) ) and the longer chain diamines (n ≥ 6) . The variations in spectral features with diamine chain length are less pronounced in dichloromethane. The spectroscopic results are consistent with the occurrence of distinct bilirubin conformations depending upon the solvent and the geometry of the interacting receptor. Based on molecular modelling two conformations are proposed. A 'ridge-tile' model similar to that observed in crystals is favoured for binding to the longer diamines, while a 'quasi-cyclic' structure is preferred for interaction with the short chain diamines

Remote sensing technique- a tool for environmental studies

Environment belongs to all and is important to all. As per definition of the Environment Protection Act, environment includes all the physical and biological surroundings and their interactions. The study of environment or rather environmental studies is a multi-disciplinary which needs knowledge interest from physical sciences (physics, chemistry, mathematics), biological sciences (botany, zoology, microbiology, biochemistry), social sciences, economics, sociology, education, geography) etc

Regimes of stratified turbulence at low Prandtl number

Quantifying transport by strongly stratified turbulence in low Prandtl number ($Pr$) fluids is critically important for the development of better models for the structure and evolution of stellar interiors. Motivated by recent numerical simulations showing strongly anisotropic flows suggestive of scale-separated dynamics, we perform a multiscale asymptotic analysis of the governing equations. We find that, in all cases, the resulting slow-fast system naturally takes a quasilinear form. Our analysis also reveals the existence of several distinct dynamical regimes depending on the emergent buoyancy Reynolds and P\'eclet numbers, $Re_b = \alpha^2 Re$ and $Pe_b = Pr Re_b$, respectively, where $\alpha$ is the aspect ratio of the large-scale turbulent flow structures, and $Re$ is the outer scale Reynolds number. Scaling relationships relating the aspect ratio, the characteristic vertical velocity, and the strength of the stratification (measured by the Froude number $Fr$) naturally emerge from the analysis. When $Pe_b \ll \alpha$, the dynamics at all scales is dominated by buoyancy diffusion, and our results recover the scaling laws empirically obtained from direct numerical simulations by Cope et al. (2020). For $Pe_b \ge O(1)$, diffusion is negligible (or at least subdominant) at all scales and our results are consistent with those of Chini et al. (2022) for strongly stratified geophysical turbulence at $Pr = O(1)$.Finally, we have identified a new regime for $\alpha \ll Pe_b \ll 1$, in which slow, large scales are diffusive while fast, small scales are not. We conclude by presenting a map of parameter space that clearly indicates the transitions between isotropic turbulence, non-diffusive stratified turbulence, diffusive stratified turbulence and viscously-dominated flows.Comment: 25 pages, 1 figur

Epithelioid trophoblastic tumor: a case report of a rare trophoblastic neoplasm

Epithelioid Trophoblastic Tumor (ETT) is a rare neoplasm of the chorionic type intermediate trophoblastic cells. It is a neoplasm of reproductive age women and usually follows a gestational event. ETT can occur at both intra uterine and extra uterine sites and can be confused with other entities such as squamous cell carcinoma, placental site nodule, placental site trophoblastic tumor etc. Hence, proper diagnosis of this tumor is necessary to avoid unnecessary, excessive treatment as surgical treatment is considered sufficient for ETT. We present a case of ETT in a 36 year old female, who came with symptoms of pain abdomen, white discharge per vaginum and a cervical mass

Primary pulmonary synovial sarcoma: a rare case report

Primary lung sarcoma is an extremely rare tumor, accounting for less than 0.5% of all lung tumors. Histological subtypes are differentiated on the basis of immunohistochemical markers, such as vimentin, desmin, actin, CD99, and epithelial membrane antigen. A 50-year-old male presented with progressively increasing shortness of breath with cough for 2 months. On Contrast Enhanced Computed Tomography (CECT) of thorax a large heterogeneous mass with multiple areas of necrosis, occupying almost whole of left hemithorax was seen. CT-guided Fine Needle Aspiration Cytology (FNAC) revealed spindle cell neoplasm. Histopathological examination revealed a spindle cell sarcoma. On immunohistochemistry the tumor cells expressed both epithelial membrane antigen and vimentin. Hence, final impression from immunohistochemistry was primary monophasic synovial sarcoma of lung