Interactors and neighbors of ULK1 complex members.

The ULK1 kinase complex plays a crucial role in autophagosome biogenesis. To identify interactors or regulators of ULK1 complex assembly influencing autophagosome biogenesis, we performed an interaction proteomics screen. Employing both affinity purification and proximity labeling of - and -terminal tagged fusion proteins coupled to quantitative mass spectrometry, we identified 317 high-confidence interactors or neighbors of the four ULK1 complex members, including both member-specific and common interactors.

Multidisciplinary approaches to study anaemia with special mention on aplastic anaemia (Review).

Anaemia is a common health problem worldwide that disproportionately affects vulnerable groups, such as children and expectant mothers. It has a variety of underlying causes, some of which are genetic. A comprehensive strategy combining physical examination, laboratory testing (for example, a complete blood count), and molecular tools for accurate identification is required for diagnosis.

The ULK1 effector BAG2 regulates autophagy initiation by modulating AMBRA1 localization.

Autophagy initiation is regulated by the ULK1 kinase complex. To gain insights into functions of the holo-complex, we generated a deep interactome by combining affinity purification- and proximity labeling-mass spectrometry of all four complex members: ULK1, ATG13, ATG101, and RB1CC1/FIP200. Under starvation conditions, the ULK1 complex interacts with several protein and lipid kinases and phosphatases, implying the formation of a signalosome.

Gold-Catalyzed Lactone Synthesis: Advancements and Insights.

Lactones represent a class of fundamental structural motifs ubiquitous in nature, holding significance across diverse scientific domains such as pharmaceuticals, natural products, drug discovery, and industry. Despite their simplicity, the synthesis of lactones has garnered considerable interest due to their pivotal roles. Gold, traditionally regarded as a noble metal, has emerged as an efficient catalyst, challenging conventional perceptions.

Comorbidity-Guided Text Mining and Omics Pipeline to Identify Candidate Genes and Drugs for Alzheimer's Disease.

Alzheimer's disease (AD), a multifactorial neurodegenerative disorder, is prevalent among the elderly population. It is a complex trait with mutations in multiple genes. Although the US Food and Drug Administration (FDA) has approved a few drugs for AD treatment, a definitive cure remains elusive.

The role(s) of community health workers in primary health care reform in Kerala, before and during the COVID 19 pandemic: a qualitative study.

Background: Accredited Social Health Activists (ASHA) are Community Health Workers (CHWs) employed by the National Health Mission of the Government of India to link the population to health facilities and improve maternal and child health outcomes in the country. The government of Kerala launched primary health reform measures in 2016 whereby Primary Health Centres (PHCs) were upgraded to Family Health Centres (FHCs). The COVID-19 pandemic in 2020 impacted essential health service delivery, including primary care services.

National Rural Health Mission reforms in light of decentralised planning in Kerala, India: a realist analysis of data from three witness seminars.

Background: The People's Planning Campaign (PPC) in the southern Indian state of Kerala started in 1996, following which the state devolved functions, finances, and functionaries to Local Self-Governments (LSGs). The erstwhile National Rural Health Mission (NRHM), subsequently renamed the National Health Mission (NHM) was a large-scale, national architectural health reform launched in 2005. How decentralisation and NRHM interacted and played out at the ground level is understudied.

Alteration in PNMA1 expression is associated with poor prognosis and tumor immune infiltration in head and neck squamous cell carcinoma.

Background: A significant percentage of the world is distressed due to the widespread and aggressive head and neck squamous cell carcinoma (HNSCC). The prognosis for people with HNSCC remains grim, despite progress in treatment techniques. This underscores the pressing demand for the discovery of novel biomarkers to enable early detection and improve prognostic categorization.

The autophagy machinery interacts with EBV capsids during viral envelope release.

Autophagy serves as a defense mechanism against intracellular pathogens, but several microorganisms exploit it for their own benefit. Accordingly, certain herpesviruses include autophagic membranes into their infectious virus particles. In this study, we analyzed the composition of purified virions of the Epstein-Barr virus (EBV), a common oncogenic γ-herpesvirus.

Autophagy protein 5 controls flow-dependent endothelial functions.

Dysregulated autophagy is associated with cardiovascular and metabolic diseases, where impaired flow-mediated endothelial cell responses promote cardiovascular risk. The mechanism by which the autophagy machinery regulates endothelial functions is complex. We applied multi-omics approaches and in vitro and in vivo functional assays to decipher the diverse roles of autophagy in endothelial cells.

Ultrafast and Controlled Capturing, Loading, and Release of Extracellular Vesicles by a Portable Microstructured Electrochemical Fluidic Device.

Extracellular vesicles (EVs) are secreted by all living cells and are found in body fluids. They exert numerous physiological and pathological functions and serve as cargo shuttles. Due to their safety and inherent bioactivity, they have emerged as versatile therapeutic agents, biomarkers, and potential drug carriers.

Trends in mechanobiology guided tissue engineering and tools to study cell-substrate interactions: a brief review.

Sensing the mechanical properties of the substrates or the matrix by the cells and the tissues, the subsequent downstream responses at the cellular, nuclear and epigenetic levels and the outcomes are beginning to get unraveled more recently. There have been various instances where researchers have established the underlying connection between the cellular mechanosignalling pathways and cellular physiology, cellular differentiation, and also tissue pathology. It has been now accepted that mechanosignalling, alone or in combination with classical pathways, could play a significant role in fate determination, development, and organization of cells and tissues.

Of primary health care reforms and pandemic responses: understanding perspectives of health system actors in Kerala before and during COVID-19.

Background: In 2016, the Government of the southern Indian state of Kerala launched the Aardram mission, a set of reforms in the state's health sector with the support of Local Self Governments (LSG). Primary Health Centres (PHCs) were slated for transformation into Family Health Centres (FHCs), with extended hours of operation as well as improved quality and range of services. With the COVID-19 pandemic emerging soon after their introduction, we studied the outcomes of the transformation from PHC to FHC and how they related to primary healthcare service delivery during COVID-19.

A review on non-Newtonian fluid models for multi-layered blood rheology in constricted arteries.

Haemodynamics is a branch of fluid mechanics which investigates the features of blood when it flows not only via blood vessels of smaller/larger diameter, but also under normal as well as abnormal flow states, such as in the presence of stenosis, aneurysm, and thrombosis. This review aims to discuss the rheological properties of blood, geometry of constrictions, dilations and the emergence of single-layered fluid to four-layered fluid models. To discuss further the influence of the aforesaid parameters on the physiologically important flow quantities, the mathematical formulation and solution methodology of the two-layered and four layered arterial blood flow problems studied by the authors (Afiqah and Sankar in ARPN J Eng Appl Sci 15:1129--1143, 2020, Comput Methods Programs Biomed 199:105907, 2021.

An arcane presentation of pustular psoriasis in pregnancy: case report.

Pustular psoriasis of pregnancy (PPP) also known as impetigo herpetiformis is a well-described dermatosis of pregnancy characterized by the fatal progression of disease for both the mother and the foetus if left untreated. A 28-year-old G2P1L1 pregnant mother at 28 weeks of gestation, came to outpatient department (OPD) with complaints of scaly skin lesions all over her body along with fever, nausea and generalised weakness. On examination, there were erythematous scaly patches in the trunk, back, hands and legs accompanied by formation of pustules in the periphery of the lesions.

TBK1 phosphorylation activates LIR-dependent degradation of the inflammation repressor TNIP1.

Limitation of excessive inflammation due to selective degradation of pro-inflammatory proteins is one of the cytoprotective functions attributed to autophagy. In the current study, we highlight that selective autophagy also plays a vital role in promoting the establishment of a robust inflammatory response. Under inflammatory conditions, here TLR3-activation by poly(I:C) treatment, the inflammation repressor TNIP1 (TNFAIP3 interacting protein 1) is phosphorylated by Tank-binding kinase 1 (TBK1) activating an LIR motif that leads to the selective autophagy-dependent degradation of TNIP1, supporting the expression of pro-inflammatory genes and proteins.

Bargaining with patriarchy through the life course: obstacles faced (and overcome) by women leaders in Kerala's health sector.

Background: The COVID-19 pandemic has helped shine the spotlight on the role of women's leadership in tackling the world's health and health system challenges. The proportion of women occupying senior leadership positions in the health sector is less compared to males, even as they constitute a vast majority of the work force. The South Indian state of Kerala is an exception to this trend, a phenomenon that we sought to understand and contextualise.

mTORC1 controls Golgi architecture and vesicle secretion by phosphorylation of SCYL1.

The protein kinase mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth and proliferation, supporting anabolic reactions and inhibiting catabolic pathways like autophagy. Its hyperactivation is a frequent event in cancer promoting tumor cell proliferation. Several intracellular membrane-associated mTORC1 pools have been identified, linking its function to distinct subcellular localizations.

Intersecting sex-related inequalities in self-reported testing for and prevalence of Non-Communicable Disease (NCD) risk factors in Kerala.

Background: Non-Communicable Diseases (NCDs) are among India's top burdens, particularly in states like Kerala, which is at an advanced stage of the epidemiological transition. Evidence in India points towards intersectional inequalities in risk factors of NCDs and testing, both of which are understudied in Kerala. We estimated the self-reported testing and prevalence of key NCD risk factors-blood pressure (BP) and blood glucose (BG) comparing Kerala men and women across educational, wealth, religion, as well as caste and tribal status subgroups.

ULK1 phosphorylation of striatin activates protein phosphatase 2A and autophagy.

The evolutionarily conserved ULK1 kinase complex acts as gatekeeper of canonical autophagy and regulates induction of autophagosome biogenesis. To better understand control of ULK1 and analyze whether ULK1 has broader functions that are also linked to the later steps of autophagy, we perform comprehensive phosphoproteomic analyses. Combining in vivo with in vitro data, we identify numerous direct ULK1 target sites within autophagy-relevant proteins that are critical for autophagosome maturation and turnover.

Combinatorial effect of plasma treatment, fiber alignment and fiber scale of poly (ε-caprolactone)/collagen multiscale fibers in inducing tenogenesis in non-tenogenic media.

Tendon being a hypocellular, low vascularized tissue often requires assistance for restoration after complete tear. Tendon tissue engineering aims in the development of suitable scaffold that could support the regeneration of tendon after damage. The success of such scaffolds is dependent on its integration with the native tissue which in turn is influenced by the cell-material interaction.

Empanelment of health care facilities under Ayushman Bharat Pradhan Mantri Jan Arogya Yojana (AB PM-JAY) in India.

Introduction: India's Pradhan Mantri Jan Arogya Yojana (PM-JAY) is the world's largest health assurance scheme providing health cover of 500,000 INR (about USD 6,800) per family per year. It provides financial support for secondary and tertiary care hospitalization expenses to about 500 million of India's poorest households through various insurance models with care delivered by public and private empanelled providers. This study undertook to describe the provider empanelment of PM-JAY, a key element of its functioning and determinant of its impact.

[1,2]- vs [2,3]-Wittig Rearrangement in Carbohydrate Derived Alkenyl Systems.

A simple and efficient strategy for the regio- and stereoselective synthesis of carbon-branched sugar derivatives is described. The successful implementation of Wittig rearrangement on substrates derived by Ferrier rearrangement of various glycals and 3--alkenyl glycals is studied extensively. A highly selective [1,2]- or [2,3]-Wittig rearrangement is revealed that provides a novel class of stereodefined 3--branched glycals and -glycosides, which are otherwise difficult to obtain.