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A menippid crab Myomenippe hardwickii (Gray, 1831) was obtained in the macrobenthic collections from Hukitola, a mangrove-associated Bay located south of Bhitarkanika, Odisha, on the east coast of India. Although the crab was reported from the coastal waters adjoining Andhra Pradesh and West Bengal, documentation of the species from Odisha remained elusive until the current study. Therefore, species diagnosis with suitable illustrations and ecological details are provided. [ABSTRACT FROM AUTHOR]

Udumbara Ghanasatwa is a classical Ayurvedic formulation prescribed for the treatment of gastritis, indigestion and diarrhoea without any scientific validation of its pharmacological action. The present study investigated the antiulcer activity of Udumbara Ghanasatwa at two graded doses by pylorus ligation model in rats. The anti-diarrhoeal activity was also evaluated in terms of the defecation amount/frequency as well as intestinal fluid enteropooling in castor oil induced diarrhoea. The Ghanasatwa exerted significant protective effects in both pylorus ligation-induced gastric ulcer and castor oil induced diarrhoeal models in a dose-dependent manner. Findings obtained in the study justified the clinical applications of Udumbara Ghanasatwa in the treatment of gastric ulcers and diarrhoea. These pharmacological effects exerted by Ghanasatwa may be attributed to the antioxidant phytoconstituents like flavonoids and tannins present in it. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Neuropathological hallmarks of AD are amyloid plaques and neurofibrillary tangles. The biomarkers used in the diagnosis of AD are mostly invasive. Established methods are available to identify biomarkers in cerebrospinal fluid (CSF) and plasma. β-amyloid (1-42) [Aβ (1-42)], total tau (T-tau) and phosphorylated tau (Ptau) are the three biomarkers present in CSF as well as plasma. Increased level of these three biomarkers is associated with AD. These biomarkers in CSF can be measured by enzyme linked immunosorbent assay (ELISA), but measuring these biomarkers in blood need more sensitive and specific assays. Dendritic proteins like neurogranin, synaptosomal associated protein 25 (SNAP-25) and synaptotagmin-1 (SYT1) in CSF can also be used as biomarkers as their level is decreased in AD. Neurofilament light (NFL) level (increased) in both CSF and plasma can serve as a biomarker for AD. Collection of CSF by lumbar puncture is a measure drawback which limits its use as a diagnostic tool. Biomarkers in non-invasive samples such as urine, saliva, hair and nail are under development and can be used in near future. Level of 8-hydroxy-2-deoxyguanosine (8-OHdG) and isoprostane in urine, cortisol level in saliva, concentration of trace elements in hair and nail can be used as biomarkers in AD. [ABSTRACT FROM AUTHOR]

Exposure to chronic stress is an important factor of neurodegeneration. Forced swimming test is a common model for chronic stress which needs validation in terms of duration of exposure and correlation of behavioural, histological and anti-oxidant status. Adult wistar albino rats (150-200 g) of both sexes were divided into two groups. Group I treated as control and Group II animals were subjected to forced swimming test for 30 minutes daily. On different days (0, 3,7,15 and 30) effect on behavioural, histological and anti-oxidant status was evaluated. Swimming stress of 30 minutes daily for 15 days significantly (p<0.05) decreased the time of fall in rotarod, locomotor activity in actophotometer, number of correct entries in radial maze, superoxide dismutase (SOD) level and significantly (p<0.05) increased the malondialdehyde (MDA) content along with prominent tissue degeneration in brain, heart, liver and kidney. The present study reveals that 30 minutes exposure to forced swimming for 15 days can be a novel model of chronic stress as it results in significant alterations in behavioural, histological and antioxidant status. [ABSTRACT FROM AUTHOR]

An attempt was made to evaluate the energy supplements for horses by gas production technique by taking 6 commonly available feeds. In the study NDF% was highest in pearl millet (32.24) and oats (32.07), followed by barley (17.93). ADF ranged from 3.42 (maize grain) to 16.45% (pearl millet); similarly maximum amount of cellulose was in pearl millet (13.90) and minimum in maize (2.88%). ADL content ranged from 0.24 (maize) to 2.98% (oats); and hemicellulos e content was highest in oats (18.27) and pearl millet (15.79). AIA content was lowest in sweet potato tuber, oats, maize, wheat and pearl millet. EE% of DM ranged from 1.73% in pearl millet to 4.03% in maize. Total ash (TA) content was highest in oats (2.83) and lowest in pearl millet (1.97). Starch% of NSC, ranged from 89.80% (wheat) to 99.43% (pearl millet). DE (Mcal/kg) varied from 3.17 (pearl millet) to 3.88 (maize). H owever, the NSC (%DM) was highest in wheat (70.17%) and l owest oats (52.78%). CP% DM varied from 24.36% (sweet potato) to 9.46% (barley). NDICP% of CP ranged from 4.16% (wheat) to 15.72% (maize). ADICP% of CP ranged from 2.05% (wheat) to 6.88% (pearl millet). SOLP % of CP was hig hest in oats (53.03), whereas lowest was in maize (13.88%). However, NPN% of SOLP was maximum in pearl millet grain (98.39%) and minimum in oats grain (20.94). In vitro true dry matter digestibility (%) was highest in sweet potato (83.94%) followed by pearl millet (83.23%), wheat grain (82.04%) and lowest in oats grain (70.44%). IVOMD followed the similar pattern as in IVDMD (%). CH4 production (g/ kg DM incubated) ranged from 6.30 (oats grain) to 12.6 (wheat). Highest methane production (g/kg TDMD and g/kg TOMD) was observed in wheat grain (14.54 and 15.30) and lowest in oats grain (10.10 and 10.62). [ABSTRACT FROM AUTHOR]

The incidence of severe malaria and malaria-specific mortality were investigated in a hospital, for miners and their families, at Tensa in the Sundergarh district of Orissa state in India. Tensa lies in area where malaria (predominantly caused by Plasmodium falciparum) is hyper-endemic. The hospital records for 1995-1999 showed that, although annual admissions for malaria increased over the study period, there were very few admissions for severe, complicated malaria and no reports of malaria-specific deaths. Most of the patients who had been admitted with cerebral malaria either came from areas around but not within the town of Tensa or were recent arrivals in the town. It appears that the outcome of malaria is influenced not only by the intensity of local transmission (which affects the immunological status of the human hosts) but also by social factors such as the education and health-seeking behaviour of the local population and the health-care facilities available. The low incidence of severe malaria observed in Tensa was probably the result of patients presenting early in the course of their illness and taking antimalarial treatment, iron supplementation and supportive therapy at the appropriate times. [ABSTRACT FROM AUTHOR]

Keeping horses in mind, six legume and two non legume fodders were evaluated on the basis of CNCPS. The total CHO (%DM) was highest in berseem, moth and groundnut haulm (64.09, 69.1 and 66.81, respectively). CA fraction was highest in mustard (37.42%) and lowest fractions of CB1 and CB2 were found in cowpea straw (6.18%) and mustard (10.59%), whereas, highest fractions of both were found in lucerne (20.96% and 33.29%). The CHO (%DM) of non-legumes ranged from 73.44% (oats) to 70.58% (maize). CB1 fractions (%CHO) ranged from 17.30% (oats) to 22.73% (maize). CB2 fraction (%CHO) ranged from 53.60% in maize to 60.07% (oats). Fraction PA (%CP) was highest in lucerne, groundnut and mustard (17.75, 15.11 and 16.98, respectively) and lowest factions PB2 was found in moth bean straw and groundnut, respectively. PB3 fractions (%CP) were maximum in groundnut haulm (31.80%) and minimum in mustard fodder and lucerne. The PC fraction (%CP) ranged from 8.73% in berseem to 15.21% in groundnut haulm. The PA fraction (%CP) was maximum in maize (25.32%) and minimum in oats (14.19%). The fraction PB1 (%CP) ranged from 7.30% in maize to 25.92% in oats. The PB3 fraction (%CP) was highest in maize (13.09%) and lowest in oats (10.39) and lucerne (15.05 %). The PC fraction (%CP) ranged from 11.12 in oats to 15.47% in maize. In the present study, lucerne can be regarded as superior, as it has higher CP and bypass protein content and lower unavailable protein fraction. [ABSTRACT FROM AUTHOR]

The objective of this study was compare the gas production and digestibility of ten forages, using rumen liquor and equine faecal liquor as the inoculum sources. The forages were lucerne, sewan hay, hedge lucerne, para grass, moth bean fodder, heteropogon, setaria grass, sugarcane tops, groundnut haulm and paddy straw. The forages were first pretreated with pepsin and amylase for 2 hr and 4 hr, respectively before incubating with equine faecal liquor for 48 hr, while the rumen liquor was directly inoculated with forages for 48 hr. The lowest IVDMD% and IVOMD% for both the species were found in case of paddy straw. The highest amount of net gas production (mM/0.2gDM) was observed in groundnut haulm by the rumen liquor, whereas lucerne produced highest net gas by equine faecal liquor and lowest net gas was recorded in hedge lucerne for both the species. Methane produced as percentage of total gas was highest in hedge lucerne in cattle, whereas lucerne produced highest methane in horses. Methane produced (g/kg DM digested) by the rumen liquor inoculation was found to be highest in lucerne and lowest was observed in moth bean straw, whereas, sugarcane tops produced the highest methane and lowest in hedge lucerne by the equine faecal liquor inoculation. The trial revealed that equines can digest low fibrous forages at par with cattle, while high fibrous forages with 90% efficiency of cattle. Moreover, the methane productions by the horses are about 1/ 3rd of that of cattle. [ABSTRACT FROM AUTHOR]

Three cases of aortic regurgitation acquired as the result of bacterial endocarditis complicating Fallot's tetralogy and pulmonary atresia have been described. One also had mitral regurgitation from a 'jet lesion' of the anterior cusp of the mitral valve. Surgical treatment of all abnormalities with aortic valve repair or replacement was undertaken in each patient and was successful in two. Difficulties in diagnosis and surgical treatment are discussed. [ABSTRACT FROM PUBLISHER]

The surgical treatment of cyanotic heart disease in the adult poses some technical difficulties in correcting severe anatomical deformities and compromised physiological states over a wide range of conditions. Various abnormalities and their surgical management have been reviewed. Forty-six patients over the age of 18 years have been operated with 10 operative deaths. Of the survivors, 63% have had excellent clinical result; 69.5% of the total group had an excellent or good result following surgery. It is concluded that the age of the patient is not a bar to the complete repair of these deformities, and all cases of adult cyanotic heart disease should be investigated with a view to surgical correction. [ABSTRACT FROM PUBLISHER]

, , 617-623. Since 1966 a conduit of homograft ascending aorta with its valve has been used for reconstruction of the right ventricular outflow. This technique has been applied to 123 operations for pulmonary autograft replacement of the aortic valve, 48 operations for correction of severe Fallot's tetralogy or pulmonary atresia, five operations for truncus arteriosus, two operations for transposition of the great arteries with ventricular septal defect, and six operations for tricuspid atresia or common ventricle. Ease of insertion and satisfactory function have encouraged us in the use of this form of conduit. [ABSTRACT FROM PUBLISHER]

In the TAR RNA of immunodeficiency viruses, an allosteric communication exists between a distant loop and a bulge. The bulge interacts with the TAT protein vital for transactivating viral RNA, while the loop interacts with cyclin-T1, contingent on TAT binding. Through extensive atomistic and free energy simulations, we investigate TAR-TAT binding in nonpathogenic bovine immunodeficiency virus (BIV) and pathogenic human immunodeficiency virus (HIV). Thermodynamic analysis reveals enthalpically driven binding in BIV and entropically favored binding in HIV. The broader global basin in HIV is attributed to binding-induced loop fluctuation, corroborated by nuclear magnetic resonance (NMR), indicating classical entropic allostery onset. While this loop fluctuation affects the TAT binding affinity, it generates a binding-competent conformation that aids subsequent effector (cyclin-T1) binding. This study underscores how two structurally similar apo-RNA scaffolds adopt distinct conformational selection mechanisms to drive enthalpic and entropic allostery, influencing protein affinity in the signaling cascade.

Combination of Pd(ii) with selected bis-monodentate ligands produces the familiar multinuclear Pd m L 2 m type self-assembled "single-cavity discrete coordination cages" (SCDCC). If the ligand provides parallel coordination vectors, then it forms a binuclear Pd 2 L 4 type cage, whereas utilization of ligands having appropriately divergent coordination vectors results in specific higher nuclear complexes. In contrast, preparation of emergent "multi-cavity discrete coordination cages" (MCDCC) using Pd(ii) and designer ligands is quite captivating where the neighboring cavities of the framework are conjoined with each other through a common metal center. A pair of conjoined binuclear Pd 2 L 4 type sub-frameworks are present in a trinuclear Pd 3 L 4 type double-cavity cage prepared from Pd(ii) and a tris-monodentate ligand having parallel coordination vectors. The present work envisioned a design to make double-cavity coordination cages having a pair of conjoined trinuclear Pd 3 L 6 type sub-frameworks. To fulfill the objective we combined Pd(ii) with a mixture of designer bis-monodentate ligand (L) and tris-monodentate ligand (L') in a 5 : 4 : 4 ratio in one pot to afford the targeted pentanuclear type cage. The choice of bis-monodentate ligand L is based on the divergent nature of the coordination vectors suitable to produce a Pd 3 L 6 type SCDCC. The tris-monodentate ligand L' having two arms is designed in such a manner that each of the arms reasonably resembles L. Study of the complexation behavior of Pd(ii) with L' provided additional guiding factors essential for the successful making of type MCDCC by integrative self-sorting. A few other MCDCC including lower symmetry versions were also prepared in the course of the work., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Cancer is positioned as a major disease, particularly for middle-aged people, which remains a global concern that can develop in the form of abnormal growth of body cells at any place in the human body. Cervical cancer, often known as cervix cancer, is cancer present in the female cervix. In the area where the endocervix (upper two-thirds of the cervix) and ectocervix (lower third of the cervix) meet, the majority of cervical cancers begin. Despite an influx of people entering the healthcare industry, the demand for machine learning (ML) specialists has recently outpaced the supply. To close the gap, user-friendly applications, such as H2O, have made significant progress these days. However, traditional ML techniques handle each stage of the process separately; whereas H2O AutoML can automate a major portion of the ML workflow, such as automatic training and tuning of multiple models within a user-defined timeframe., Methods: Thus, novel H2O AutoML with local interpretable model-agnostic explanations (LIME) techniques have been proposed in this research work that enhance the predictability of an ML model in a user-defined timeframe. We herein collected the cervical cancer dataset from the freely available Kaggle repository for our research work. The Stacked Ensembles approach, on the other hand, will automatically train H2O models to create a highly predictive ensemble model that will outperform the AutoML Leaderboard in most instances. The novelty of this research is aimed at training the best model using the AutoML technique that helps in reducing the human effort over traditional ML techniques in less amount of time. Additionally, LIME has been implemented over the H2O AutoML model, to uncover black boxes and to explain every individual prediction in our model. We have evaluated our model performance using the findprediction() function on three different idx values (i.e., 100, 120, and 150) to find the prediction probabilities of two classes for each feature. These experiments have been done in Lenovo core i7 NVidia GeForce 860M GPU laptop in Windows 10 operating system using Python 3.8.3 software on Jupyter 6.4.3 platform., Results: The proposed model resulted in the prediction probabilities depending on the features as 87%, 95%, and 87% for class '0' and 13%, 5%, and 13% for class '1' when idx&#95;value=100, 120, and 150 for the first case; 100% for class '0' and 0% for class '1', when idx&#95;value= 10, 12, and 15 respectively. Additionally, a comparative analysis has been drawn where our proposed model outperforms previous results found in cervical cancer research., Competing Interests: The authors declare there are no competing interests., (©2024 Prusty et al.)

Mycobacterium tuberculosis ( Mtb ) employs a multifaceted arsenal to elude host defense mechanisms, including those associated with autophagy and lysosome function. Within the realm of host-pathogen interactions, NCOR1, a well-recognized transcriptional co-repressor, is known to associate with a multitude of protein complexes to effect the repression of a diverse spectrum of genes. However, its role in regulating macroautophagy/autophagy, lysosome biogenesis, and, by extension, Mtb pathogenesis remains unexplored. The depletion of NCOR1 assumes a pivotal role in the control of the AMPK-MTOR-TFEB signaling axis, thereby fine-tuning cellular ATP homeostasis. This finely orchestrated adjustment further alters the profile of proteins involved in autophagy and lysosomal biogenesis through its master regulator, TFEB, culminating in the increased Mtb survival within the host milieu. Furthermore, the treatment of NCOR1-depleted cells with either rapamycin, antimycin A, or metformin demonstrates a capacity to restore the TFEB activity and LC3-II levels, consequently restoring the capacity of host cells to clear Mtb . Additionally, exogenous NCOR1 expression rescues the AMPK-MTOR-TFEB signaling axis and essentially the autophagic induction machinery. Overall, these findings demonstrate a crucial role of NCOR1 in regulating Mtb pathogenesis within myeloid cells and sheds light toward its involvement in the development of novel host-directed therapies.

Mycobacterium tuberculosis (Mtb) defends host-mediated killing by repressing the autophagolysosome machinery. For the first time, we report NCoR1 co-repressor as a crucial host factor, controlling Mtb growth in myeloid cells by regulating both autophagosome maturation and lysosome biogenesis. We found that the dynamic expression of NCoR1 is compromised in human peripheral blood mononuclear cells (PBMCs) during active Mtb infection, which is rescued upon prolonged anti-mycobacterial therapy. In addition, a loss of function in myeloid-specific NCoR1 considerably exacerbates the growth of M. tuberculosis in vitro in THP1 differentiated macrophages, ex vivo in bone marrow-derived macrophages (BMDMs), and in vivo in NCoR1MyeKO mice. We showed that NCoR1 depletion controls the AMPK-mTOR-TFEB signalling axis by fine-tuning cellular adenosine triphosphate (ATP) homeostasis, which in turn changes the expression of proteins involved in autophagy and lysosomal biogenesis. Moreover, we also showed that the treatment of NCoR1 depleted cells by Rapamycin, Antimycin-A, or Metformin rescued the TFEB activity and LC3 levels, resulting in enhanced Mtb clearance. Similarly, expressing NCoR1 exogenously rescued the AMPK-mTOR-TFEB signalling axis and Mtb killing. Overall, our data revealed a central role of NCoR1 in Mtb pathogenesis in myeloid cells., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2023 Biswas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To identify occupational hazards and hazard control strategies adopted by inland fishers of Odisha state in India., Methods: Information on occupational hazards faced by fishers was collected by personal interviews with 90 riverine and reservoir fishers of Odisha. Through qualitative discussions with key informants and review of literature, a list of occupational hazards were prepared and classified into physical, ergonomics, psychosocial, and natural. Responses were quantified, and descriptive statistics were used for data analysis., Results: Occupational hazards faced by fishers were physical (94%), ergonomic (75%), psychosocial (50%), and natural (34%) in nature. Physical hazards include sharp fishing instruments, uneven surfaces, high temperatures, and wet/slippery areas on the vessel along with the presence of snake/leech/crocodile/fish fin rays. About 97% of reservoir and 90% of the riverine fishers reported physical hazards leading to cuts, fractures, dehydration, headache, sunburn, snakebite, leech bite, crocodile bite, and injuries due to fish fin rays. Heavy nature of work and force exerting activities caused pain in the upper back (50%), shoulders (45%), and lower back (41%). Regarding psychosocial hazard, stress (31%), and anxiety (23%) was reported. Common reasons for this were uncertainty in fish catch and extended working hours, causing tiredness, headache, dizziness, and fatigue. Natural hazards like cyclones, floods, and excessive rain caused financial loss and damage to fishing nets and boats. Regarding personal protective equipment (PPE), floating buoys were used by 26% of riverine and 43% of reservoir fishers to avoid drowning., Conclusion: Occupational hazards in the inland fishing sector were identified as physical, ergonomic, psychosocial, and natural. No particular hazard control strategy was reported to be used. Integrating the occupational safety measures in the fisheries policies is thus needed.

Dendritic cells (DCs) undergo rapid metabolic reprogramming to generate signal-specific immune responses. The fine control of cellular metabolism underlying DC immune tolerance remains elusive. We have recently reported that NCoR1 ablation generates immune-tolerant DCs through enhanced IL-10, IL-27 and SOCS3 expression. In this study, we did comprehensive metabolic profiling of these tolerogenic DCs and identified that they meet their energy requirements through enhanced glycolysis and oxidative phosphorylation (OXPHOS), supported by fatty acid oxidation-driven oxygen consumption. In addition, the reduced pyruvate and glutamine oxidation with a broken TCA cycle maintains the tolerogenic state of the cells. Mechanistically, the AKT-mTOR-HIF-1α-axis mediated glycolysis and CPT1a-driven β-oxidation were enhanced in these tolerogenic DCs. To confirm these observations, we used synthetic metabolic inhibitors and found that the combined inhibition of HIF-1α and CPT1a using KC7F2 and etomoxir, respectively, compromised the overall transcriptional signature of immunological tolerance including the regulatory cytokines IL-10 and IL-27. Functionally, treatment of tolerogenic DCs with dual KC7F2 and etomoxir treatment perturbed the polarization of co-cultured naïve CD4 + T helper (Th) cells towards Th1 than Tregs, ex vivo and in vivo. Physiologically, the Mycobacterium tuberculosis (Mtb) infection model depicted significantly reduced bacterial burden in BMcDC1 ex vivo and in CD103 + lung DCs in Mtb infected NCoR1 DC-/- mice. The spleen of these infected animals also showed increased Th1-mediated responses in the inhibitor-treated group. These findings suggested strong involvement of NCoR1 in immune tolerance. Our validation in primary human monocyte-derived DCs (moDCs) showed diminished NCOR1 expression in dexamethasone-derived tolerogenic moDCs along with suppression of CD4 + T cell proliferation and Th1 polarization. Furthermore, the combined KC7F2 and etomoxir treatment rescued the decreased T cell proliferative capacity and the Th1 phenotype. Overall, for the first time, we demonstrated here that NCoR1 mediated control of glycolysis and fatty acid oxidation fine-tunes immune tolerance versus inflammation balance in murine and human DCs., Competing Interests: Declaration of completing interest The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Groundwater is usually utilized as a drinking water asset everywhere. Therefore, groundwater defilement by poisonous radioactive metals such as uranium (VI) is a major concern due to the increase in nuclear power plants as well as their by-products which are released into the watercourses. Waste Uranium (VI) can be regarded as a by-product of the enrichment method used to produce atomic energy, and the hazard associated with this is due to the uranium radioactivity causing toxicity. To manage these confronts, there are so many techniques that have been introduced but among those adsorptions is recognized as a straightforward, successful, and monetary innovation, which has gotten major interest nowadays, despite specific drawbacks regarding operational as well as functional applications. This review summarizes the various adsorbents such as Bio-adsorbent/green materials, metal oxide-based adsorbent, polymer based adsorbent, graphene oxide based adsorbent, and magnetic nanomaterials and discuss their synthesis methods. Furthermore, this paper emphasis on adsorption process by various adsorbents or modified forms under different physicochemical conditions. In addition to this adsorption mechanism of uranium (VI) onto different adsorbent is studied in this article. Finally, from the literature reviewed conclusion have been drawn and also proposed few future research suggestions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Micronutrients are essential for plants. Their growth, productivity and reproduction are directly influenced by the supply of micronutrients. Currently, there are eight trace elements considered to be essential for higher plants: Fe, Zn, Mn, Cu, Ni, B, Mo, and Cl. Possibly, other essential elements could be discovered because of recent advances in nutrient solution culture techniques and in the commercial availability of highly sensitive analytical instrumentation for elemental analysis. Much remains to be learned about the physiology of micronutrient absorption, translocation and deposition in plants, and about the functions they perform in plant growth and development. With the recent advancements in the proteomic and molecular biology tools, researchers have attempted to explore and address some of these questions. In this review, we summarize the current knowledge of micronutrients in plants and the proteomic/genomic approaches used to study plant nutrient deficiency and toxicity., Competing Interests: The authors declare no conflict of interest.

Tight control of gene regulation in dendritic cells (DCs) is important to mount pathogen specific immune responses. Apart from transcription factor binding, dynamic regulation of enhancer activity through global transcriptional repressors like Nuclear Receptor Co-repressor 1 (NCoR1) plays a major role in fine-tuning of DC responses. However, how NCoR1 regulates enhancer activity and gene expression in individual or multiple Toll-like receptor (TLR) activation in DCs is largely unknown. In this study, we did a comprehensive epigenomic analysis of murine conventional type-I DCs (cDC1) across different TLR ligation conditions. We profiled gene expression changes along with H3K27ac active enhancers and NCoR1 binding in the TLR9, TLR3 and combined TLR9 + TLR3 activated cDC1. We observed spatio-temporal activity of TLR9 and TLR3 specific enhancers regulating signal specific target genes. Interestingly, we found that NCoR1 differentially controls the TLR9 and TLR3-specific responses. NCoR1 depletion specifically enhanced TLR9 responses as evident from increased enhancer activity as well as TLR9-specific gene expression, whereas TLR3-mediated antiviral response genes were negatively regulated. We validated that NCoR1 KD cDC1 showed significantly decreased TLR3 specific antiviral responses through decreased IRF3 activation. In addition, decreased IRF3 binding was observed at selected ISGs leading to their decreased expression upon NCoR1 depletion. Consequently, the NCoR1 depleted cDC1 showed reduced Sendai Virus (SeV) clearance and cytotoxic potential of CD8 + T cells upon TLR3 activation. NCoR1 directly controls the majority of these TLR specific enhancer activity and the gene expression. Overall, for the first time, we revealed NCoR1 mediates transcriptional control towards TLR9 as compared to TLR3 in cDC1., (© 2022. The Author(s).)

Background: Hereditary angioedema (HAE) is a genetic disorder characterized by re-occurring swelling episodes called "attacks," usually in the limbs, face, airways, and intestinal tract. New prophylactic therapies have reduced the frequency of these attacks. This study describes results from a literature review and clinician interviews assessing patient HAE symptom experiences and timing, and then evaluates whether existing patient-reported outcome (PRO) tools adequately reflect this experience., Methods: A targeted literature review as well as interviews with key opinion leaders (KOLs), were conducted to capture information about the patient experience and their symptoms. An assessment of various PROs was then conducted to determine how well they each covered HAE symptoms and impacts., Results: Nineteen HAE symptoms were identified. KOLs reported that patients on prophylactic therapy experienced some symptoms indicating an attack was imminent, but then never experienced an attack. The comparison of the different PROs found that the Hereditary Angioedema Patient-Reported Outcome was the instrument that most thoroughly examined the symptoms of patients with HAE., Conclusions: Given the introduction of new prophylactic therapies, further research is needed to determine the effect of being attack-free for longer periods of time on health-related quality of life., (© 2022. The Author(s).)

Accurate and timely diagnosis of primary immunodeficiencies (PID) is an ongoing effort. Individuals with PID can be severely impacted by their disease and many experience chronic complications, treatment burden, and reduced quality of life (QoL). This review focuses on the impact of delayed diagnosis and treatment burden on patient QoL and outcomes. Adults tend to experience longer delays in diagnosis than pediatric populations. The median diagnostic delay has reduced over recent decades, but remains high for some antibody deficiency variants, such as common variable immunodeficiency. The largest burden impacting QoL tends to be poorly controlled disease and persistent chronic conditions rather than treatment burden. Hospitalization, physician/emergency room visits, and bronchiectasis were the most expensive PID complications prior to diagnosis and cost analyses estimate cost reductions once appropriate treatment is initiated. A combination of poor awareness, lack of infrastructure, and resources supporting national registries play a major role in delayed diagnosis., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Biological macromolecules often exhibit correlations in fluctuations involving distinct domains. This study decodes their functional implications in RNA-protein recognition and target-specific binding. The target search of a peptide along RNA in a viral TAR-Tat complex is closely monitored using atomistic simulations, steered molecular dynamics simulations, free energy calculations, and a machine-learning-based clustering technique. An anticorrelated domain fluctuation is identified between the tetraloop and the bulge region in the apo form of TAR RNA that sets a hierarchy in the domain-specific fluctuations at each binding event and that directs the succeeding binding footsteps. Thus, at each binding footstep, the dynamic partner selects an RNA location for binding where it senses a higher fluctuation, which is conventionally reduced upon binding. This event stimulates an alternate domain fluctuation, which then dictates sequential binding footstep/s and thus the search progresses. Our cross-correlation maps show that the fluctuations relay from one domain to another specific domain until the anticorrelation between those interdomain fluctuations sustains. Artificial attenuation of that hierarchical domain fluctuation inhibits specific RNA binding. The binding is completed with the arrival of a few long-lived water molecules that mediate slightly distant RNA-protein sites and finally stabilize the overall complex. The study underscores the functional importance of naturally designed fluctuating RNA motifs (bulge, tetraloop) and their interplay in dictating the directionality of the search in a highly dynamic environment.

Biofilm formation on medical implants and devices has been a severe concern that results in their impaired performance and life-threatening complications. Thus, development of novel functional coatings for infection prone surfaces with biofilm inhibiting characteristics is of prime significance considering the rapid emergence of multidrug resistant bacteria. Herein we present a novel nanocomposite derived from Graphene Oxide (GO) and a newly developed functional Ionic liquid (IL) obtained through a metathesis reaction between a triarylmethane dye hexamethyl pararosaniline chloride or crystal violet (CV) and sodium dodeceyl sulfate (SDS) to yield [CV][DS] (hexamethyl pararosaniline dodecyl sulfate). This highly biocompatible [CV][DS]-GO nanocomposite exhibit more than four times improved antibacterial activity in comparison to bare GO against both gram negative Escherichia coli (E. coli) and gram positive Staphylococcus aureus (S. aureus). As suggested by XRD, FTIR and UV absorption and SEM results improved activity of [CV][DS]-GO nanocomposite is ascribed to the synergistic effect of reduced nanocomposite sheet thickness, enhanced amphiphilicity imparted by dodecylsulfate (DS), exposed active ArN + groups of CV and some inherent functionalities of GO. This is also complemented by the ruptured and diffused S. aureus cell walls as observed in bacterial SEM result. In contrast, the nanocomposites of the precursors with GO do not demonstrate any significant antibacterial effect. Coatings developed using GO upon infestation with E. coli revealed significant biofilm formation after 48 and 72 h of incubation while [CV][DS]-GO coated surface demonstrated no colony growth under similar circumstances. Thus, [CV][DS]-GO nanocomposite coatings exhibit excellent resistance to bacterial growth even up to 72 h incubation signifying its bactericidal effect. Therefore, the developed nanocomposite may be considered as one of the improved antibacterial wash resistant coating material for biomedical devices and surfaces susceptible to to biofilm formation., (Copyright © 2021 Elsevier B.V. All rights reserved.)