Background: Hypertensive disorders of pregnancy are an elusive group of diseases with multifactorial etiopathologies and varied manifestation. Abnormal pre pregnancy lipid profile is shown to have a ...positive correlation with endothelial dysfunction which in turn leads to development of hypertensive disorder of pregnancy.Methods: A total of 222 pregnant women who were aged between 18-35 years, with no obstetric and medical risk factors and less than 16 weeks of gestation who gave informed written consent were recruited for the study. Their baseline demographics and fasting blood samples were collected, blood samples were centrifuged, and serum was stored at -80-degree celsius. Patients were followed up till delivery and those with hypertensive disorders in pregnancy (n=22) was identified, defined as case. Control was selected after matching for body mass index and frozen serum samples were analyzed.Results: Overall incidence of hypertensive disorders in pregnancy in the study group was 12.4%. The mean early trimester fasting lipid values were higher in patients who developed hypertensive disorders, difference in mean between cases and controls was TC - 16.25 mg/dl (p-0.061), TGL- 21.45 mg/dl (p-0.143), LDL- 2.4 mg/dl (p-0.82) and for HDL 4.55 mg/dl (p-0.25). However, on stratification of early trimester fasting lipid level based on National Cholesterol Education Program (NCEP) criteria, Total cholesterol level greater than 160 mg/dl showed an odds ratio of 12.66 (p-0). Patients with early trimester fasting total cholesterol levels greater than 160mg/dl has a higher risk of developing hypertensive disorder in pregnancy.
We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and ...whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations.
•Comprehensive molecular analysis is performed on 66 kidney chromophobe cases•Global molecular patterns provide clues as to this cancer’s cell of origin•mtDNA sequencing reveals loss-of-function mutations in NADH dehydrogenase subunits•Genomic structural rearrangements involving TERT promoter region are assessed
Davis et al. describe the landscape of somatic genomic alterations of chromophobe renal cell carcinomas, showing that changes in mitochondrial function are an inherent component of the disease biology and identifying genomic rearrangement as a mechanism for elevated TERT expression.
Interferon gamma (IFNγ) is a critical cytokine known for its diverse roles in immune regulation, inflammation, and tumor surveillance. However, while IFNγ levels were elevated in sera of most newly ...diagnosed acute myeloid leukemia (AML) patients, its complex interplay in AML remains insufficiently understood. We aim to characterize these complex interactions through comprehensive bulk and single-cell approaches in bone marrow of newly diagnosed AML patients. We identify monocytic AML as having a unique microenvironment characterized by IFNγ producing T and NK cells, high IFNγ signaling, and immunosuppressive features. IFNγ signaling score strongly correlates with venetoclax resistance in primary AML patient cells. Additionally, IFNγ treatment of primary AML patient cells increased venetoclax resistance. Lastly, a parsimonious 47-gene IFNγ score demonstrates robust prognostic value. In summary, our findings suggest that inhibiting IFNγ is a potential treatment strategy to overcoming venetoclax resistance and immune evasion in AML patients.
The interaction between the anti-cancer drug Palbociclib (PAL) and calf-thymus DNA (CT-DNA) was investigated using various biophysical techniques in a physiological buffer (pH 7.4). It was found that ...PAL intercalated into the base pairs of CT-DNA as evidenced from the results of UV-Vis, fluorescence, circular dichroism (CD), competitive binding assay with ethidium bromide (EB) and Hoechst 33258, KI quenching study, the effect of denaturing agent and viscosity measurements. The magnitude of binding constants (10
6
M
−1
) at different temperatures suggested strong binding between PAL and CT-DNA during complexation. The observed ΔH
o
> 0 and ΔS
o
> 0 indicated that the binding process is primarily driven by hydrophobic interactions. Molecular docking studies indicated partial intercalation of pyridopyrimidine ring between the base pairs of DNA. Free energy surface (FES) analysis derived from metadynamics simulation studies revealed the PAL-induced cleavage of DNA, which was confirmed by gel electrophoresis experiments.
Communicated by Ramaswamy H. Sarma
Emphasis on utilizing the industrial waste/discarded materials can be brought about by discovering innovative methods of disposal. One such a way of waste disposal can be through utilizing them in ...concrete production as a filler material or pozzolana. In this regard, the present study proposes to use the aluminium dross and granular iron slag as partial replacement materials for cement and natural sand, respectively, to develop eco-concrete. Nine mixes were produced with different proportions of cement, aluminium dross, sand and granular iron slag content. The aluminium dross was replaced at 5, 10, 15 and 20% of the weight of the cement. Initially, the optimal substitution percentage of aluminium dross was found without the substitution of iron slag based on the strength results. Later, by adopting the optimal aluminium dross percentage with cement, the granular iron slag was partially substituted at 10, 20, 30 and 40% of natural sand to find the overall optimal blend. The strength and durability properties of the M40 grade concrete employing these two admixture combinations were analysed. It was noticed that the strength and durability properties of the eco-concrete produced by incorporating aluminium dross −5% and iron slag −20% were comparable to that of conventional concrete. Furthermore, from the toxicity analysis, it was seen that the leaching of heavy and trace elements from the eco-concrete was negligibly small and within the limits. In near future, the cost-effective, eco-friendly materials and technologies can be opted as a perpetual strategy to overcome severe material shortages for resource conservation and economy.
The aim of the UniProt Knowledgebase is to provide users with a comprehensive, high-quality and freely accessible set of protein sequences annotated with functional information. In this publication ...we describe enhancements made to our data processing pipeline and to our website to adapt to an ever-increasing information content. The number of sequences in UniProtKB has risen to over 227 million and we are working towards including a reference proteome for each taxonomic group. We continue to extract detailed annotations from the literature to update or create reviewed entries, while unreviewed entries are supplemented with annotations provided by automated systems using a variety of machine-learning techniques. In addition, the scientific community continues their contributions of publications and annotations to UniProt entries of their interest. Finally, we describe our new website (https://www.uniprot.org/), designed to enhance our users' experience and make our data easily accessible to the research community. This interface includes access to AlphaFold structures for more than 85% of all entries as well as improved visualisations for subcellular localisation of proteins.
Delivery of food and drug molecules is a challenging field of research with growing interests. Due to concerns on solubility, stability, and bioavailability, numerous techniques have been explored to ...identify effective and sustainable approaches. The large surface area and wide blood supply made the lungs a prominent route for the delivery of therapeutic molecules. Several drug molecules have been effectively delivered through the pulmonary route, and this review focuses on the pulmonary delivery of food-derived therapeutic molecules through aerosols. Various methods have been used to fabricate aerosols; their mechanism of deposition and absorption in the lungs involves intricacies in terms of a range of factors including their physical and aerodynamic properties, apart from the conditions of the body. This review attempts to elaborate on these aspects, apart from providing a status report on the current scenario of delivering therapeutic molecules through the pulmonary route. Importantly, highlighting regulatory aspects, challenges associated with the delivery of food-derived molecules such as aerosols are presented, giving lead for directions for future research.
Abstract
The aim of the UniProt Knowledgebase is to provide users with a comprehensive, high-quality and freely accessible set of protein sequences annotated with functional information. In this ...article, we describe significant updates that we have made over the last two years to the resource. The number of sequences in UniProtKB has risen to approximately 190 million, despite continued work to reduce sequence redundancy at the proteome level. We have adopted new methods of assessing proteome completeness and quality. We continue to extract detailed annotations from the literature to add to reviewed entries and supplement these in unreviewed entries with annotations provided by automated systems such as the newly implemented Association-Rule-Based Annotator (ARBA). We have developed a credit-based publication submission interface to allow the community to contribute publications and annotations to UniProt entries. We describe how UniProtKB responded to the COVID-19 pandemic through expert curation of relevant entries that were rapidly made available to the research community through a dedicated portal. UniProt resources are available under a CC-BY (4.0) license via the web at https://www.uniprot.org/.
Wnts play pivotal roles during development and in the mature nervous system. However, the mechanism by which Wnts traffic between cells has remained elusive. Here we demonstrate a mechanism of Wnt ...transmission through release of exosome-like vesicles containing the Wnt-binding protein Evenness Interrupted/Wntless/Sprinter (Evi/Wls/Srt). We show that at the
Drosophila larval neuromuscular junction (NMJ), presynaptic vesicular release of Evi is required for the secretion of the Wnt, Wingless (Wg). We also show that Evi acts cell-autonomously in the postsynaptic Wnt-receiving cell to target dGRIP, a Wg-receptor-interacting protein, to postsynaptic sites. Upon Evi loss of function, dGRIP is not properly targeted to synaptic sites, interfering with postsynaptic Wnt signal transduction. These findings uncover a previously unknown cellular mechanism by which a secreted Wnt is transported across synapses by Evi-containing vesicles and reveal trafficking functions of Evi in both the Wnt-producing and the Wnt-receiving cells.
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