FunRes: resolving tissue-specific functional cell states based on a cell-cell communication network model.

The functional specialization of cell types arises during development and is shaped by cell-cell communication networks determining a distribution of functional cell states that are collectively important for tissue functioning. However, the identification of these tissue-specific functional cell states remains challenging. Although a plethora of computational approaches have been successful in detecting cell types and subtypes, they fail in resolving tissue-specific functional cell states. To address this issue, we present FunRes, a computational method designed for the identification of functional cell states. FunRes relies on scRNA-seq data of a tissue to initially reconstruct the functional cell-cell communication network, which is leveraged for partitioning each cell type into functional cell states. We applied FunRes to 177 cell types in 10 different tissues and demonstrated that the detected states correspond to known functional cell states of various cell types, which cannot be recapitulated by existing computational tools. Finally, we characterize emerging and vanishing functional cell states in aging and disease, and demonstrate their involvement in key tissue functions. Thus, we believe that FunRes will be of great utility in the characterization of the functional landscape of cell types and the identification of dysfunctional cell states in aging and disease.

Alternate splicing of transcripts upon Mycobacterium tuberculosis infection impacts the expression of functional protein domains.

Previously, we reported that infection of human macrophages with Mycobacterium tuberculosis (Mtb) results in massive alterations in the pattern of RNA splicing in the host. The finding gained significance since alternate spliced variants of a same gene may have substantially different structure, function, stability, interaction partners, localization, and so forth, owing to inclusion or exclusion of specific exons. To establish a proof-of-concept; on how infection-induced RNA splicing could impact protein functions, here we used RNA-seq data from THP-1 macrophages that were infected with clinical isolate of Mtb. In addition to re-establishing the fact that Mtb infection may cause strain specific alterations in RNA splicing, we also developed a new analysis pipeline resulting in characterization of domain maps of the transcriptome post-infection. For the sake of simplicity, we restricted our analysis to all the kinases in the human genome and considered only pfam classified protein domains and checked their frequency of inclusion or exclusion due to alternate splicing across the conditions and time points. We report massive alterations in the domain architecture of most regulated proteins across the entire kinases highlighting the physiological importance of such an understanding. This study paves way for more detailed analysis of different functional classes of proteins and perturbations to their domain architecture as a consequence of mycobacterial infections. Such analysis would yield unprecedented depth to our understanding of host-pathogen interaction and allow in a more systematic manner targeting of host pathways for controlling the infections. © 2018 The Authors. IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 70(9):845-854, 2018.

Lesion Sterilization Tissue Repair: A Review.

As part of lesion sterilization and tissue restoration (LSTR), treatment for primary molars affected by extensive periapical pathosis and extreme resorption entails the use of a triple antibiotic mixture in an appropriate medium. In-depth explanation of all components of LSTR is the main focus of this review of the literature.

Prevalence of alcohol dependence syndrome in the patients of acute pancreatitis: A cross-sectional study.

Background: Acute pancreatitis (AP) is the main reason for mortality and morbidity. Numerous studies have shown a link between chronic alcohol usage and AP. However, there are few studies on the percentage of patients developing AP as a result of dependent patterns of drinking and associated risk factors. Aim: This study aimed to study the prevalence and impact of risk factors of alcohol dependence syndrome with AP patients hospitalized in tertiary care facilities. Materials and Methods: This is a cross-sectional observational study. Sociodemographic and clinical data were taken from patients with AP after consent. Eighty-five patients with AP who met the inclusion criteria were involved after each participant had clinical evaluation using the modified Marshall score, the Alcohol Use Disorder Identification Test, and the Severity of Alcohol Dependence Questionnaire (SAD-Q). The outcomes were tabulated and analyzed using Statistical Package for the Social Sciences (SPSS) software. Results: 38.8% of patients with AP were found to have features of alcohol dependence syndrome. Higher values of mean corpuscular volume (MCV), serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), Gamma-glutamyl transferase (GGT), and uric acid were associated with a greater propensity to have AP. The severity of alcohol dependence syndrome and AP was not associated. Conclusion: AP is potentially a fatal disease. In this study, 38.8% of AP patients had alcohol dependence syndrome. There was no statistical association between the severity of AP and alcohol dependence syndrome, though high values of MCV, SGOT, SGPT, and GGT were at greater risk of developing AP. As a result, alcohol dependence syndrome should be examined in all individuals with AP.

Depression among rheumatoid arthritis patients and barriers to seeking professional help: An observational study.

Background: A few studies have reported the association of rheumatoid arthritis (RA) with emotional changes including anxiety and depression. There is a paucity of Indian studies in this area. Aim: To assess depression and its correlates in diagnosed cases of RA. Materials and Methods: This was a cross-sectional and hospital-based study. A total of 70 patients with RA fulfilled the inclusion and exclusion criteria. Their demographic characteristics were recorded. They were individually assessed with the Clinical Disease Activity Index, Numerical Pain Rating Scale, Barriers to Access Care Evaluation, and Beck Depression Inventory. Statistical analysis was undertaken with SPSS. Results: In the patients with RA the prevalence of depression was 44.2%. Analysis revealed that there was a significant positive correlation between depression with the severity of RA. Barriers to help-seeking were mainly attitudinal rather than stigma-related or instrumental barriers. Conclusion: In the RA patients, the prevalence of depression was 44.2%. Clinical disease activity and the pain index were higher in patients with depression.

Transcriptional and Chromatin Accessibility Profiling of Neural Stem Cells Differentiating into Astrocytes Reveal Dynamic Signatures Affected under Inflammatory Conditions.

Astrocytes arise from multipotent neural stem cells (NSCs) and represent the most abundant cell type of the central nervous system (CNS), playing key roles in the developing and adult brain. Since the differentiation of NSCs towards a gliogenic fate is a precisely timed and regulated process, its perturbation gives rise to dysfunctional astrocytic phenotypes. Inflammation, which often underlies neurological disorders, including neurodevelopmental disorders and brain tumors, disrupts the accurate developmental process of NSCs. However, the specific consequences of an inflammatory environment on the epigenetic and transcriptional programs underlying NSCs' differentiation into astrocytes is unexplored. Here, we address this gap by profiling in mice glial precursors from neural tissue derived from early embryonic stages along their astrocytic differentiation trajectory in the presence or absence of tumor necrosis factor (TNF), a master pro-inflammatory cytokine. By using a combination of RNA- and ATAC-sequencing approaches, together with footprint and integrated gene regulatory network analyses, we here identify key differences during the differentiation of NSCs into astrocytes under physiological and inflammatory settings. In agreement with its role to turn cells resistant to inflammatory challenges, we detect Nrf2 as a master transcription factor supporting the astrocytic differentiation under TNF exposure. Further, under these conditions, we unravel additional transcriptional regulatory hubs, including Stat3, Smad3, Cebpb, and Nfkb2, highlighting the interplay among pathways underlying physiological astrocytic developmental processes and those involved in inflammatory responses, resulting in discrete astrocytic phenotypes. Overall, our study reports key transcriptional and epigenetic changes leading to the identification of molecular regulators of astrocytic differentiation. Furthermore, our analyses provide a valuable resource for understanding inflammation-induced astrocytic phenotypes that might contribute to the development and progression of CNS disorders with an inflammatory component.

Green Surfactants (Biosurfactants): A Petroleum-Free Substitute for Sustainability-Comparison, Applications, Market, and Future Prospects.

Surfactants are a group of amphiphilic molecules (i.e., having both hydrophobic and hydrophilic domains) that are a vital part of nearly every contemporary industrial process such as in agriculture, medicine, personal care, food, and petroleum. In general surfactants can be derived from (i) petroleum-based sources or (ii) microbial/plant origins. Petroleum-based surfactants are obvious results from petroleum products, which lead to petroleum pollution and thus pose severe problems to the environment leading to various ecological damages. Thus, newer techniques have been suggested for deriving surfactant molecules and maintaining environmental sustainability. Biosurfactants are surfactants of microbial or plant origins and offer much added advantages such as high biodegradability, lesser toxicity, ease of raw material availability, and easy applicability. Thus, they are also termed "green surfactants". In this regard, this review focused on the advantages of biosurfactants over the synthetic surfactants produced from petroleum-based products along with their potential applications in different industries. We also provided their market aspects and future directions that can be considered with selections of biosurfactants. This would open up new avenues for surfactant research by overcoming the existing bottlenecks in this field.