Structures of Drosophila cryptochrome and mouse cryptochrome1 provide insight into circadian function.

Drosophila cryptochrome (dCRY) is a FAD-dependent circadian photoreceptor, whereas mammalian cryptochromes (CRY1/2) are integral clock components that repress mCLOCK/mBMAL1-dependent transcription. We report crystal structures of full-length dCRY, a dCRY loop deletion construct, and the photolyase homology region of mouse CRY1 (mCRY1). Our dCRY structures depict Phe534 of the regulatory tail in the same location as the photolesion in DNA-repairing photolyases and reveal that the sulfur loop and tail residue Cys523 plays key roles in the dCRY photoreaction. Our mCRY1 structure visualizes previously characterized mutations, an NLS, and MAPK and AMPK phosphorylation sites. We show that the FAD and antenna chromophore-binding regions, a predicted coiled-coil helix, the C-terminal lid, and charged surfaces are involved in FAD-independent mPER2 and FBXL3 binding and mCLOCK/mBMAL1 transcriptional repression. The structure of a mammalian cryptochrome1 protein may catalyze the development of CRY chemical probes and the design of therapeutic metabolic modulators.

A Poly-ADP-Ribose Trigger Releases the Auto-Inhibition of a Chromatin Remodeling Oncogene.

DNA damage triggers chromatin remodeling by mechanisms that are poorly understood. The oncogene and chromatin remodeler ALC1/CHD1L massively decompacts chromatin in vivo yet is inactive prior to DNA-damage-mediated PARP1 induction. We show that the interaction of the ALC1 macrodomain with the ATPase module mediates auto-inhibition. PARP1 activation suppresses this inhibitory interaction. Crucially, release from auto-inhibition requires a poly-ADP-ribose (PAR) binding macrodomain. We identify tri-ADP-ribose as a potent PAR-mimic and synthetic allosteric effector that abrogates ATPase-macrodomain interactions, promotes an ungated conformation, and activates the remodeler's ATPase. ALC1 fragments lacking the regulatory macrodomain relax chromatin in vivo without requiring PARP1 activation. Further, the ATPase restricts the macrodomain's interaction with PARP1 under non-DNA damage conditions. Somatic cancer mutants disrupt ALC1's auto-inhibition and activate chromatin remodeling. Our data show that the NAD+-metabolite and nucleic acid PAR triggers ALC1 to drive chromatin relaxation. Modular allostery in this oncogene tightly controls its robust, DNA-damage-dependent activation.

Impact of inflammatory cytokine and adipokine gene variations in the development of HIV-associated lipodystrophy.

Cytokines affect lipid and glucose metabolism and also alter the body's habitus. They play a role in the development of lipodystrophy syndrome. Adipocytes secrete the pro-inflammatory cytokines IL-1, TNF-α and IL-6. The plasma cytokine concentration is associated with the percentage and distribution of fat tissue in the body. The metabolic disturbances are strongly associated with increased levels of pro-inflammatory cytokines (IL-1, IL-6 and TNF-α). Plasma levels of cytokines such as TNF-α, IL-6 and leptin were found to be increased while plasma resistin levels were found to be variable in patients suffering from obesity and type II diabetes mellitus. Until now, limited information has been available on the polymorphism of cytokine and adipokine genes in patients of HIV-associated lipodystrophy (HIVLD), which can contribute to individual variations in susceptibility to metabolic diseases, especially to HIVLD. Hence, we studied the association of cytokine and adipokine gene polymorphisms in various diseases and their impact on HIVLD. We carry out an extensive search using several databases, including PubMed, EMBASE and Google Scholar. The distribution of cytokine and adipokine gene polymorphisms and their expression levels varied among various populations. We examined the variants of cytokine and adipokine genes, which can contribute to individual variations in susceptibility to metabolic diseases, especially to HIVLD. In the current review, we present a brief account of the risk factors of HIVLD, the pathogenesis of HIVLD and the polymorphism of cytokine and adipokine genes in various diseases with special reference to their impact on HIVLD.

A comparison of the quality of images of chest X-ray between handheld portable digital X-ray & routinely used digital X-ray machine.

Background & objectives: Chest X-ray (CXR) is an important screening tool for pulmonary tuberculosis (TB). Accessibility to CXR facilities in difficult-to-reach and underserved populations is a challenge. This can potentially be overcome by deploying digital X-ray machines that are portable. However, these portable X-ray machines need to be validated before their deployment in the field. Here, we compare the image quality of CXR taken by a newly developed handheld X-ray machine with routinely used reference digital X-ray machine through the conduct of a feasibility study. Methods: A total of 100 participants with suspected pulmonary TB were recruited from the outpatient departments of a medical college and a community health centre in Agra. Each participant underwent CXR twice, once with each machine. Both sets of de-identified images were independently read by two radiologists, who were blinded to the type of X-ray machine used. The primary outcome was agreement between image qualities produced by these two machines. Results: The intra-observer (radiologist) agreements regarding the status of the 15 CXR parameters ranged between 74 per cent and 100 per cent, with an unweighted mean of 87.2 per cent (95% confidence interval: 71.5-100). The median Cohen's kappa values for intra-observer agreement were 0.62 and 0.67 for radiologists 1 and 2, respectively. In addition, on comparison of the overall median score of quality of the image, the handheld machine images had a higher score for image quality. Interpretation & conclusions: The current study shows that a handheld X-ray machine, which is easy to use and can potentially be carried to any area, produces X-ray images with quality that is comparable to digital X-ray machines routinely used in health facilities.

Epigenetic Editing: Repurposing for Rescue.

The epigenome editing framework provides an engineering approach to explore chromatin-based gene expression mechanisms. However, therapeutic utility of epigenetic editing-based systems has been lacking. A report in Cell (Liu et. al., 2018) shows that epigenetic editors can revert abnormal heterochromatin formation at the gene promoter leading to restoration of FMR1 gene expression, functionally rescuing fragile X syndrome (FXS), an otherwise unamenable genetic disorder.

Post-Translational Modification, Phase Separation, and Robust Gene Transcription.

A few recent reports reveal fundamental new insights into the intricate regulatory mechanisms that govern RNA polymerase II (Pol II)-mediated gene transcription. Whereas a histidine-rich domain (HRD) triggers phase separation, promoting transcription elongation, a phosphatase switch promotes transcription termination. A paradigm that might govern the underlying mechanisms leading to robust gene transcription is now starting to emerge.

Intestinal viral infections of nSARS-CoV2 in the Indian community: Risk of virus spread in India.

In December 2019, novel severe acute respiratory syndrome coronavirus 2 (nSARS-CoV-2) virus outbreaks emerged from Wuhan, China, and spread all over the world, including India. Molecular diagnosis of Coronavirus Disease 2019 (COVID) 19 for densely and highly populated countries like India is time-consuming. A few reports have described the successful diagnosis of nSARS-CoV-2 virus from sewage and wastewater samples contaminated with fecal matter, suggesting the diagnosis of COVID 19 from the same to raise an alarm about the community transmission of virus for implementation of evacuation and lockdown strategies. So far, the association between the detection of virus and its concentration in stool samples with severity of the disease and the presence or absence of gastrointestinal symptoms have been rarely reported. We led the search utilizing multiple databases, specifically PubMed (Medline), EMBASE, and Google Scholar. We conducted a literature survey on gastrointestinal infection and the spread of this virus through fecal-oral transmission. Reports suggested that the existence and persistence of nSARS-CoV-2 in anal/rectal swabs and stool specimens for a longer period of time than in nasopharyngeal swabs provides a strong tenable outcome of gastrointestinal contamination and dissemination of this infection via potential fecal-oral transmission. This review may be helpful to conduct further studies to address the enteric involvement and excretion of nSARS-CoV-2 RNA in feces and control the community spread in both COVID-19 patients ahead of the onset of symptoms and in asymptomatic individuals through wastewater and sewage surveillance as an early indication of infection. The existence of the viral genome and active viral particle actively participate in genomic variations. Hence, we comprehended the enteric spread of different viruses amongst communities with special reference to nSARS-CoV-2.

ACF takes the driver's seat.

ISWI family chromatin remodeling enzymes generate regularly spaced nucleosome arrays. In a recent Nature report, Hwang et al. (2014) describe how ACF gauges the length of linker DNA when deciding to accelerate nucleosome sliding or to put on the brakes.

Predicting COVID-19 statistics using machine learning regression model: Li-MuLi-Poly.

In this paper, linear regression (LR), multi-linear regression (MLR) and polynomial regression (PR) techniques are applied to propose a model Li-MuLi-Poly. The model predicts COVID-19 deaths happening in the United States of America. The experiment was carried out on machine learning model, minimum mean square error model, and maximum likelihood ratio model. The best-fitting model was selected according to the measures of mean square error, adjusted mean square error, mean square error, root mean square error (RMSE) and maximum likelihood ratio, and the statistical t-test was used to verify the results. Data sets are analyzed, cleaned up and debated before being applied to the proposed regression model. The correlation of the selected independent parameters was determined by the heat map and the Carl Pearson correlation matrix. It was found that the accuracy of the LR model best-fits the dataset when all the independent parameters are used in modeling, however, RMSE and mean absolute error (MAE) are high as compared to PR models. The PR models of a high degree are required to best-fit the dataset when not much independent parameter is considered in modeling. However, the PR models of low degree best-fits the dataset when independent parameters from all dimensions are considered in modeling.

Principles and Applications of Nucleic Acid Strand Displacement Reactions.

Dynamic DNA nanotechnology, a subfield of DNA nanotechnology, is concerned with the study and application of nucleic acid strand-displacement reactions. Strand-displacement reactions generally proceed by three-way or four-way branch migration and initially were investigated for their relevance to genetic recombination. Through the use of toeholds, which are single-stranded segments of DNA to which an invader strand can bind to initiate branch migration, the rate with which strand displacement reactions proceed can be varied by more than 6 orders of magnitude. In addition, the use of toeholds enables the construction of enzyme-free DNA reaction networks exhibiting complex dynamical behavior. A demonstration of this was provided in the year 2000, in which strand displacement reactions were employed to drive a DNA-based nanomachine (Yurke, B.; et al. Nature 2000, 406, 605-608). Since then, toehold-mediated strand displacement reactions have been used with ever increasing sophistication and the field of dynamic DNA nanotechnology has grown exponentially. Besides molecular machines, the field has produced enzyme-free catalytic systems, all DNA chemical oscillators and the most complex molecular computers yet devised. Enzyme-free catalytic systems can function as chemical amplifiers and as such have received considerable attention for sensing and detection applications in chemistry and medical diagnostics. Strand-displacement reactions have been combined with other enzymatically driven processes and have also been employed within living cells (Groves, B.; et al. Nat. Nanotechnol. 2015, 11, 287-294). Strand-displacement principles have also been applied in synthetic biology to enable artificial gene regulation and computation in bacteria. Given the enormous progress of dynamic DNA nanotechnology over the past years, the field now seems poised for practical application.

Constructed wetland for improved wastewater management and increased water use efficiency in resource scarce SAT villages: a case study from Kothapally village, in India.

Evaluation a field-scale of constructed wetland (CW) for the treatment of rural wastewater (WW), in resource-scarce semi-arid tropic (SAT) villages, to provide improved wastewater management and increased water use efficiency, was the main objective of this study. A CW was commissioned in Kothapally village of Telangana to treat the wastewater generated from 100 households. The CW was vegetated with Typha latifolia and Canna indica. Average COD, sulfate and inorganic nitrogen removal efficiencies observed were 65%, 60% and 67% respectively, for the study period (one year). Removal efficiency for total coliform was consistently above 80%. The treated wastewater was stored in a farm pond and was utilized for irrigation in the nearby agricultural fields (0.6 ha). This perennial source of water, helped the nearby farmers to cultivate two additional crops, chickpea during rabi and sweetcorn during summer. The assured availability of water reduced their vulnerability to dry spells during the kharif by providing means for lifesaving irrigation. The biomass harvested from the constructed wetland was used as fodder for the livestock. A net additional income of Rs.70,000 (∼US$1,000) was realized by the farmers using the treated wastewater for cultivation. Similar constructed wetland-based wastewater management system can be scaled up across water scarce semi-arid tropics. Novelty statementField-scale performance evaluation of constructed wetland based wastewater treatment in a semi-arid tropic village is scarce in the literature. The work presented gives a feasibility assessment for this technology critical for its wide-scale application to augment rural wastewater management in resource poor villages.

Polymorphisms in miRNAs Gene (146a, 149, 196a) and Susceptibility to ARV-associated Hepatotoxicity.

BACKGROUND: Micro RNAs act as a regulatory layer for pharmacogenomics-related gene ex-pression. It could play a role in the efficacy and toxicity of the drug. The SNPs in miRNA genes are linked with different functional consequences. METHODS: Hence, we examined the miR (146a G/C, 149C/T, and 196aC/T) polymorphisms in 34 pa-tients with hepatotoxicity, 123 patients without hepatotoxicity, and 155 healthy controls using a PCR-RFLP method. RESULTS: In patients with hepatotoxicity, miR196aCT genotype and combined genotype GCT showed a risk for hepatotoxicity severity with borderline significance (OR=2.08, P=0.07; OR=2.88, P=0.06). While comparing between patients with hepatotoxicity and healthy controls, the combined genotypes CCC and GCT have shown a susceptibility to hepatotoxicity severity (OR=2.89, P=0.05; OR=2.60, P=0.09). The miR196TT genotype was associated with the individuals of advanced HIV disease stage (OR=3.68, P=0.04). In HIV patients who consumed alcohol and did not have hepatotoxicity, the miR 196aCT genotype showed susceptibility to acquisition of hepatotoxicity with borderline significance (OR=2.36, P=0.06). DISCUSSION: The miR149TT and 196aTT genotypes showed a risk of acquisition of hepatotoxicity to nevirapine usage among HIV patients without hepatotoxicity (OR=4.19, P=0.07; OR=1.97, P=0.84). In HIV patients with and without hepatotoxicity, the miR 196aCT genotype showed a risk of acquisition of hepatotoxicity and its severity to the combined use of alcohol and nevirapine, respectively (OR=14.18, P=0.08; OR=2.29, P=0.08). In multivariate logistic regression, taking nevirapine, 196aCT genotype had an independent risk factor for hepatotoxicity severity (OR=5.98, P=0.005; OR=2.38, P=0.05).Conclusion: In conclusion, miR196aC/T polymorphism and combined genotypes GCT and CCC may facilitate the risk for acquisition of hepatotoxicity and its severity.

The histone chaperone sNASP binds a conserved peptide motif within the globular core of histone H3 through its TPR repeats.

Eukaryotic chromatin is a complex yet dynamic structure, which is regulated in part by the assembly and disassembly of nucleosomes. Key to this process is a group of proteins termed histone chaperones that guide the thermodynamic assembly of nucleosomes by interacting with soluble histones. Here we investigate the interaction between the histone chaperone sNASP and its histone H3 substrate. We find that sNASP binds with nanomolar affinity to a conserved heptapeptide motif in the globular domain of H3, close to the C-terminus. Through functional analysis of sNASP homologues we identified point mutations in surface residues within the TPR domain of sNASP that disrupt H3 peptide interaction, but do not completely disrupt binding to full length H3 in cells, suggesting that sNASP interacts with H3 through additional contacts. Furthermore, chemical shift perturbations from(1)H-(15)N HSQC experiments show that H3 peptide binding maps to the helical groove formed by the stacked TPR motifs of sNASP. Our findings reveal a new mode of interaction between a TPR repeat domain and an evolutionarily conserved peptide motif found in canonical H3 and in all histone H3 variants, including CenpA and have implications for the mechanism of histone chaperoning within the cell.

Editorial for Advanced Antennas for Wireless Communication Systems.

In recent years, there has been a significant expansion in wireless communication, evolving into a global network connecting billions of entities, including individuals and enterprises [...].

Assessment of energy cane bagasse-derived cellulosic microfiber hydrogels on the growth of potted chili peppers.

Energy cane (Saccharum spp.) bagasse, a type of biomass waste, is often underutilized, burned, or left to dispose of itself. This research aimed to evaluate the potential of converting this bagasse into high-value cellulosic microfiber hydrogels (CMH) for water conservation and potted chili (Capsicum annuum) plant growth. CMH offers a biodegradable alternative to synthetic polyacrylamide (PA) hydrogels and provides the dual benefit of improved water use efficiency and reduced environmental impact due to their ability to naturally break down in the soil. In this study, CMH and PA hydrogels were compared for water retention value (WRV), and reswelling kinetics (RK), as well as their effects on plant height, leaf count, root-to-shoot ratios (R:S ratio), and soil moisture retention. Two versions of CMH, CMH65 and CMH60, were prepared with varying cellulose-chitosan ratios: 65:35 and 60:40, respectively. The hydrogels were tested at four concentrations (0, 0.5, 1.0, and 2.0% w/w) by being mixed in Promix® soil. Observations were recorded over a 16-day period without additional water. Also, the WRV of hydrogels at 240 min and RK (10-180 min) were compared over three swelling-deswelling cycles. The PA hydrogel exhibited higher WRV (exceeding 450%) compared to CMH (45%). However, PA led to reduced plant height, leaf count, and R:S ratio when compared to higher concentrations of CMH65 and CMH60. In general, CMH60 (0.5% and 2%) exhibited superior plant growth. All hydrogels exhibited a significant decrease (p < 0.05) in WRV across successive cycles. Notably, during cycle 2, both CMH65 and CMH60 peaked in WRV at 10 and 20 min, respectively, compared to cycle 1. This study demonstrates the potential of bagasse-derived hydrogels as a value-added product for water conservation and crop growth.

Development of metasurface based hyperthermia lens applicator for heating of cancerous tissues.

Numerous designs and methods have been examined to improve penetration depth (PD), but there is a need for research to explore the potential increase in PD through uniform heating, a compact applicator, and low input power. This paper presents metasurface based hyperthermia lens applicator with water bolus for uniform heating of cancerous tissues. The proposed applicator consists of a stacked spiral antenna and a spiral-shaped frequency selective surface as a superstrate. The spiral antenna and superstrate are optimized on a low cost FR4 substrate having a size of 32 × 32 × 3.27mm3 and 10 × 10 × 1.6mm3 (size of the unit cell), respectively. The proposed applicator is simulated with heterogeneous phantom (skin, fat, and muscle layers) and with the Gustav voxel model with and without a water bolus layer. The number of unit cells in the superstrate is optimized to direct the maximum energy toward the tumor location. The performance study of the applicator is carried out in terms of specific absorption rate, PD, and effective field size. Further, thermal analysis is carried out with 1.9 W of input power at the antenna port, and the highest 44.7 °C temperature rise is obtained. The cancerous tissue's (tumor) surrounding temperature is between 41 and 45 °C, which is adequate for efficient hyperthermia treatment. Finally, the proposed metasurface hyperthermia lens applicator is fabricated and experimentally validated in a mimicked phantom's presence. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-023-00300-z.

A prospective multi-centric open clinical trial of homeopathy in diabetic distal symmetric polyneuropathy.

OBJECTIVES: To evaluate homeopathic treatment in the management of diabetic distal symmetric polyneuropathy. METHODS: A prospective multi-centric clinical observational study was carried out from October 2005 to September 2009 by Central Council for Research in Homeopathy (CCRH) (India) at its five institutes/units. Patients suffering from diabetes mellitus (DM) and presenting with symptoms of diabetic polyneuropathy (DPN) were screened, investigated and were enrolled in the study after fulfilling the inclusion and exclusion criteria. Patients were evaluated by the diabetic distal symmetric polyneuropathy symptom score (DDSPSS) developed by the Council. A total of 15 homeopathic medicines were identified after repertorizing the nosological symptoms and signs of the disease. The appropriate constitutional medicine was selected and prescribed in 30, 200 and 1 M potency on an individualized basis. Patients were followed up regularly for 12 months. RESULTS: Out of 336 patients (167 males and 169 females) enrolled in the study, 247 patients (123 males and 124 females) were analyzed. All patients who attended at least three follow-up appointments and baseline curve conduction studies were included in the analysis.). A statistically significant improvement in DDSPSS total score (p = 0.0001) was found at 12 months from baseline. Most objective measures did not show significant improvement. Lycopodium clavatum (n = 132), Phosphorus (n = 27) and Sulphur (n = 26) were the medicines most frequently prescribed. Adverse event of hypoglycaemia was observed in one patient only. CONCLUSION: This study suggests homeopathic medicines may be effective in managing the symptoms of DPN patients. Further studies should be controlled and include the quality of life (QOL) assessment.

Ectopic expression of Atleafy in Brassica juncea cv. Geeta for early flowering.

High temperature stress during pod filling severely affects the yield of Brassica juncea. Early flowering can evade the terminal heat stress and result in early maturity of the crop. In this study, a regeneration and transformation protocol has been standardized for B. juncea cv. Geeta. Hypocotyl from 5-day-old seedlings were used as explants. Of the various combinations of auxins and cytokinins tried along with Murashige and Skoog's (Physiol Plant 15:473-497, 1962) medium, MS + IAA (0.2 mg/l) + BA (3 mg/l) proved best for shoot regeneration with 89.9 % regeneration efficiency. To induce early flowering Leafy gene from Arabidopsis thaliana was transformed using Agrobacterium mediated transformation method. After 12 weeks transgenic plants showed flowering in vitro whereas their untransformed counterpart did not flower even after 16 weeks. The maximum transformation frequency was 4 %.

Design of customized implants and 3D printing of symmetric and asymmetric cranial cavities.

A methodology has been developed in this work to design customized cranial implants from computed tomography (CT) scan images for symmetric as well as asymmetric defects. The two-dimensional CT scan images were converted into three-dimensional geometric models using software packages. Two cases of cranial cavities at different locations were considered for implant design using two different approaches. Case 1 is having a symmetric cranial cavity while Case 2 has an asymmetric frontal cranial cavity. The craniums with defects were 3D reconstructed. Customized cranial implants were made for the two cases. In Case 1, symmetry was used to design the cranial implant. Symmetry cannot be used in Case 2. In Case 2, the implant was designed by blending from the surface available adjacent to the missing portion of the cranium. 3D reconstructed bone models and customized implants were 3D printed in poly-lactic acid (PLA) using a fused deposition modeling process for form and fit evaluation. Finite element analysis was performed to compare the mechanical behavior of bone, and the two biomaterials - polyether ether ketone (PEEK), and Ti6Al4V. Static structural finite element analysis was performed to simulate the impact of falling off a bicycle with an impact on the cranial implants in the two cases. The load was modeled as a normal force acting on the surface of the implant. It was found that the stresses in the titanium alloy are comparable to those of PEEK for both the cases. However, the strains and deformation were found to be much smaller compared to those in PEEK. Therefore, the titanium alloy is the material of choice for both the cases among the materials under consideration. The designed implants are solid hence may face the challenge in bone ingrowth. In future studies, the implant can be made porous by incorporating a lattice structure to enhance osseointegration and promote bone ingrowth. Implants for both symmetric and asymmetric defect cases in cranium were successfully designed.

People's perceptions on COVID-19 vaccination: an analysis of twitter discourse from four countries.

More than six and half million people have died as a result of the COVID-19 pandemic till Dec 2022. Vaccination is the most effective means to prevent mortality and infection attributed to COVID-19. Identifying public attitudes and perceptions on COVID-19 vaccination is essential to strengthening the vaccination programmes. This study aims to identify attitudes and perceptions of twitter users towards COVID-19 vaccinations in four different countries. A sentiment analysis of 663,377 tweets from October 2020 to September 2022 from four different countries (i.e., India, South Africa, UK, and Australia) was conducted. Text mining using roBERTA (Robustly Optimized Bert Pretraining approach) python library was used to identify the polarity of people's attitude as "negative", "positive" or "neutral" based on tweets. A sample of 2000 tweets (500 from each country) were thematically analysed to explore the people's perception concerning COVID-19 vaccines across the countries. The attitudes towards COVID-19 vaccines varied by countries. Negative attitudes were observed to be highest in India (58.48%), followed by United Kingdom (33.22%), Australia (31.42%) and South Africa (28.88%). Positive attitudes towards vaccines were highest in the United Kingdom (21.09%). The qualitative analysis yielded eight themes namely (i) vaccine shortages, (ii) vaccine side-effects, (iii) distrust on COVID-19 vaccines, (iv) voices for vaccine equity, (v) awareness about vaccines, (vi) myth busters, (vii) vaccines work and (viii) vaccines are safe. The twitter discourse reflected the evolving situation of COVID-19 pandemic and vaccination strategies, lacunae and positives in the respective countries studied.