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Complex structure formation inside or through turbid media is a challenging task due to refractive index inhomogeneity, random light scattering, and speckle noise formation. In this article, we have coupled the data regression model in the R-squared metric and used its advantages as a fitness function in the genetic algorithm to advance the resolution and structural uniformity. As a compatible system with the binary genetic algorithm, we have presented a cost-effective iterative wavefront shaping system-design with binary phase modulation using an affordable ferroelectric liquid crystal (FLC) based binary-phase spatial light modulator (SLM). R-squared metric in the genetic algorithm is analyzed to optimize the binary phase mask, and the prototype system based on iterative binary phase modulation has been validated with a 120-grit ground glass diffuser and fresh chicken tissues of thickness 307 μ m and 812 μ m . The detailed results show that the proposed cost-effective wavefront shaping system with data regression model assisted R-squared fitness function can construct high-resolution multiple complex hetero-structures simultaneously in 3D volume using an optimized single phase-mask. [ABSTRACT FROM AUTHOR]

Complex structure formation inside or through turbid media is a challenging task due to refractive index inhomogeneity, random light scattering, and speckle noise formation. In this article, we have coupled the data regression model in the R-squared metric and used its advantages as a fitness function in the genetic algorithm to advance the resolution and structural uniformity. As a compatible system with the binary genetic algorithm, we have presented a cost-effective iterative wavefront shaping system-design with binary phase modulation using an affordable ferroelectric liquid crystal (FLC) based binary-phase spatial light modulator (SLM). R-squared metric in the genetic algorithm is analyzed to optimize the binary phase mask, and the prototype system based on iterative binary phase modulation has been validated with a 120-grit ground glass diffuser and fresh chicken tissues of thickness 307 μ m and 812 μ m . The detailed results show that the proposed cost-effective wavefront shaping system with data regression model assisted R-squared fitness function can construct high-resolution multiple complex hetero-structures simultaneously in 3D volume using an optimized single phase-mask. [ABSTRACT FROM AUTHOR]

The work is focused on examining the effect of the weld groove geometry on microstructure, mechanical behaviour, residual stresses and distortion of Alloy 617/P92 steel dissimilar metal weld (DMW) joints. Manual multi-pass tungsten inert gas welding with ERNiCrCoMo-1 filler was employed to fabricate the DMW for two different groove designs: Narrow V groove (NVG) and Double V groove (NVG). The microstructural examination suggested a heterogeneous microstructure evolution at the interface of the P92 steel and ERNiCrCoMo-1 weld, including the macrosegregation and element diffusion near the interface. The interface structure included the beach parallel to the fusion boundary at the P92 steel side, the peninsula connected to the fusion boundary and the island within the weld metal and partially melted zone along Alloy 617 fusion boundary. An uneven distribution of beach, peninsula and island structures along the fusion boundary of P92 steel was confirmed from optical and SEM images of interfaces. The major diffusion of the Fe from P92 steel to ERNiCrCoMo-1 weld and Cr, Co, Mo, and Ni from ERNiCrCoMo-1 weld to P92 steel were witnessed from SEM/EDS and EMPA map. The Mo-rich M6C and Cr-rich M23C6 phases were detected in inter-dendritic areas of the weld metal using the weld's SEM/EDS, XRD and EPMA study, which formed due to the rejection of Mo from the core to inter-dendritic locations during solidification. The other phases detected in the ERNiCrCoMo-1 weld were Ni3(Al, Ti), Ti(C, N), Cr7C3 and Mo2C. A variation in the microstructure of weld metal from top to root and also along the transverse direction in terms of composition and dendritic structure and also due to the composition gradient between dendrite core and inter-dendritic areas, a significant variation in hardness of weld metal was observed from both top to root and also in the transverse direction. The peak hardness was measured in CGHAZ of P92 while the minimum was in ICHAZ of P92 steel. Tensile test studies of both NVG and DVG welds joint demonstrated that failure occurred at P92 steel in both, room-temperature and high-temperature tensile tests and ensured the welded joint's applicability for advanced ultra-supercritical applications. However, the strength of the welded joint for both types of joints was measured as lower than the strength of the base metals. In Charpy impact testing of NVG and DVG welded joints, specimens failed in two parts with a small amount of plastic deformation and impact energy of 99 ± 4 J for the NVG welds joint and 91 ± 3 J for the DVG welded joint. The welded joint met the criteria for boiler applications in terms of impact energy (minimum 42 J as per European Standard EN ISO15614-1:2017 and 80 J as per fast breeder reactor application). In terms of microstructural and mechanical properties, both welded joints are acceptable. However, the DVG welded joint showed minimum distortion and residual stresses compared to the NVG welded joint. [ABSTRACT FROM AUTHOR]

A thermoregulating smart textile based on phase change material (PCM) polyethylene glycol (PEG) was prepared by chemically grafting carboxyl-terminated PEG onto cotton. Further deposits of graphene oxide (GO) nanosheets were made on the PEG grafted cotton (PEG-g-Cotton) to improve the thermal conductivity of the fabric and to block harmful UV radiation. The GO-PEG-g-Cotton was characterized by Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), Raman spectroscopy, X-ray diffraction (XRD), x-ray photoelectron spectroscopy (XPS), and field emission-scanning electron microscopy (FE-SEM). With an enthalpy of 37 and 36 J/g, respectively, the DSC data revealed that the functionalized cotton's melting and crystallization maxima occurred at 58 °C and 40 °C, respectively. The thermogravimetric analysis (TGA) presented that GO-PEG-g-Cotton was thermally more stable in comparison to pure cotton. The thermal conductivity of PEG-g-Cotton increased to 0.52 W/m K after GO deposition, while pure cotton conductivity was measured as 0.045 W/m K. The improvement in the UV protection factor (UPF) of GO-PEG-g-Cotton was observed indicating excellent UV blocking. This temperature-regulating smart cotton offers a high thermal energy storage capability, better thermal conductivity, thermal stability, and excellent UV protection. [ABSTRACT FROM AUTHOR]

This present study demonstrated the preparation of a highly crystalline anatase (ana) form of titanium oxide (TiO2) doped silk nanocrystal (SNC) nanohybrid (ana-TCS) of diameter (7.5 ± 1.4 nm) by the sol–gel method using titanium (IV) butoxide as the hydrolysis material. This prepared nanohybrid with surface hydroxyl groups acted as a co-initiator for the synthesis of poly(L-lactic acid) (PLLA)-g-ana-TSC nanocomposite with grafted PLLA chains via the in situ polymerization technique, using tin-octoate as a catalyst. The fabricated nanocomposite had a high number average molecular weight of 83 kDa with good processibility. This prepared nanocomposite was hydrophobic in nature, with a contact angle of 105°, which was further enhanced to 122 ± 1° when processed via electrospinning technique into a non-woven fabric. The prepared nanocomposite could degrade up to 43% methylene blue dye in 15 days. This nanocomposite showed no significant molecular weight reduction after 1 h of aqeous treatment, which could be attributed to its hydrophobic nature, inhibiting its degradation. However, 50% degradation was observed for the nanocomoposite whereas, PLLA demonstrated 25% degradation in 15 days, after its end-of-life. Thus, this study revealed that the in situ synthesized PLA-ana-TCS nanocomposite could be targeted for use as a hydrophobic, self-cleaning, dye-degradable fabric. [ABSTRACT FROM AUTHOR]

Crocus sativus L. (saffron) is a globally used expensive spice. There are a few countries like Iran, Greece, Morocco, Spain, Italy, Turkey, France, Switzerland, Pakistan, China, Japan and Australia where this spice is cultivated and exported to other countries. India contributes 5% of the world's total production of which 90% is supplied only from its Jammu and Kashmir (J&K) regions. In India, the production of saffron from J&K is 3.83 tonnes whereas its annual demand is approximately 100 tonnes. In this country, there are geographical regions that have similar environmental and ecological conditions to J&K and possess the possibility of introducing this crop. Identification of such regions can be made using Ecological Niche Modelling (ENM). Therefore, 'MaxEnt' ENM was carried out using 103 environmental variables, 20 presence data and topographic parameters (elevation, slope and aspect) to find suitable regions for saffron production in unconventional areas of India. The achieved area under the curve for the model was 0.99. The precipitation and temperature were the main environmental variable influencing its cultivation. The saffron was sowed in these new modelled locations in India representing its various states such as Himachal Pradesh, Uttarakhand, Arunachal Pradesh, Sikkim, Manipur and Tamil Nadu. The quality, as well as yield of saffron produced in some of these regions, were evaluated and found at par with the saffron grown traditionally in India. Based on the promising results obtained in this work, we are expanding saffron cultivation to more modelled areas in India to meet our national demand. [ABSTRACT FROM AUTHOR]

Omics-based tools were coupled with bioinformatics for a systeomics analysis of two biopharma cell types: Chinese hamster ovary (M-CHO and CHO-K1) and SP2/0. Exponential and stationary phase samples revealed more than 10,000 transcripts and 6000 proteins across these two manufacturing cell lines. A statistical comparison of transcriptomics and proteomics data identified downregulated genes involved in protein folding, protein synthesis and protein metabolism, including PPIA-cyclophilin A, HSPD1, and EIF3K, in M-CHO compared to SP2/0 while cell cycle and actin cytoskeleton genes were reduced in SP2/0. KEGG pathway comparisons revealed glycerolipids, glycosphingolipids, ABC transporters, calcium signaling, cell adhesion, and secretion pathways depleted in M-CHO while retinol metabolism was upregulated. KEGG and IPA also indicated apoptosis, RNA degradation, and proteosomes enriched in CHO stationary phase. Alternatively, gene ontology analysis revealed an underrepresentation in ion and potassium channel activities, membrane proteins, and secretory granules including Stxbpt2, Syt1, Syt9, and Cma1 proteins in M-CHO. Additional enrichment strategies involving ultracentrifugation, biotinylation, and hydrazide chemistry identified over 4000 potential CHO membrane and secretory proteins, yet many secretory and membrane proteins were still depleted. This systeomics pipeline has revealed bottlenecks and potential opportunities for cell line engineering in CHO and SP2/0 to improve their production capabilities. [ABSTRACT FROM AUTHOR]

G-quadruplex (G4) structures are considered a promising therapeutic target in cancer. Since Ayurveda, Piperine has been known for its medicinal properties. Piperine shows anticancer properties by stabilizing the G4 motif present upstream of the c-myc gene. This gene belongs to a group of proto-oncogenes, and its aberrant transcription drives tumorigenesis. The transcriptional regulation of the c-myc gene is an interesting approach for anticancer drug design. The present study employed a chemical similarity approach to identify Piperine similar compounds and analyzed their interaction with cancer-associated G-quadruplex motifs. Among all Piperine analogs, PIP-2 exhibited strong selectivity, specificity, and affinity towards c-myc G4 DNA as elaborated through biophysical studies such as fluorescence emission, isothermal calorimetry, and circular dichroism. Moreover, our biophysical observations are supported by molecular dynamics analysis and cellular-based studies. Our study showed that PIP-2 showed higher toxicity against the A549 lung cancer cell line but lower toxicity towards normal HEK 293 cells, indicating increased efficacy of the drug at the cellular level. Biological evaluation assays such as TFP reporter assay, quantitative real-time PCR (qRT- PCR), and western blotting suggest that the Piperine analog-2 (PIP-2) stabilizes the G-quadruplex motif located at the promoter site of c-myc oncogene and downregulates its expression. In conclusion, Piperine analog PIP-2 may be used as anticancer therapeutics as it affects the c-myc oncogene expression via G-quadruplex mediated mechanism. [ABSTRACT FROM AUTHOR]

Tuberculosis is caused by the pathogenic bacterium Mycobacterium tuberculosis (Mtb) and remains the leading cause of death by infection world-wide. The Mtb genome encodes a disproportionate number of twenty cytochrome P450 enzymes, of which the essential enzyme cytochrome P450 121A1 (CYP121A1) remains a target of drug design efforts. CYP121A1 mediates a phenol coupling reaction of the tyrosine dipeptide cyclo-L-Tyr-L-Tyr (cYY). In this work, a structure and function investigation of dimerization was performed as an overlooked feature of CYP121A1 function. This investigation showed that CYP121A1 dimers form via intermolecular contacts on the distal surface and are mediated by a network of solvent-exposed hydrophobic residues. Disruption of CYP121A1 dimers by site-directed mutagenesis leads to a partial loss of specificity for cYY, resulting in an approximate 75% decrease in catalysis. 19F labeling and nuclear magnetic resonance of the enzyme FG-loop was also combined with protein docking to develop a working model of a functional CYP121A1 dimer. The results obtained suggest that participation of a homodimer interface in substrate selectivity represents a novel paradigm of substrate binding in CYPs, while also providing important mechanistic insight regarding a relevant drug target in the development of novel anti-tuberculosis agents. [ABSTRACT FROM AUTHOR]

The steno-endemic species of genus Decalepis are highly threatened by destructive wild harvesting. The medicinally important fleshy tuberous roots of Decalepis hamiltonii are traded as substitute, to meet the international market demand of Hemidesmus indicus. In addition, the tuberous roots of all three species of Decalepis possess similar exudates and texture, which challenges the ability of conventional techniques alone to perform accurate species authentication. This study was undertaken to generate DNA barcodes that could be utilized in monitoring and curtailing the illegal trade of these endangered species. The DNA barcode reference library was developed in BOLD database platform for candidate barcodes rbcL, matK, psbA-trnH, ITS and ITS2. The average intra-specific variations (0–0.27%) were less than the distance to nearest neighbour (0.4–11.67%) with matK and ITS. Anchoring the coding region rbcL in multigene tiered approach, the combination rbcL + matK + ITS yielded 100% species resolution, using the least number of loci combinations either with PAUP or BLOG methods to support a character-based approach. Species-specific SNP position (230 bp) in the matK region that is characteristic of D. hamiltonii could be used to design specific assays, enhancing its applicability for direct use in CITES enforcement for distinguishing it from H. indicus. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

On 7 February 2021, Chamoli district (Uttarakhand, India) was devastated by a deadly rock-ice avalanche that led to a large causality of more than 200 people and a huge economic loss. We found noteworthy sequence of precursory signals of main failure/detachment preceded by a dynamic nucleation phase. The rock-ice avalanche appears to have been initiated by seismic precursors which were continuously active for 2:30 h prior to main detachment. The seismic amplitude, frequency characteristics and signal-to-noise ratio variation of detected tremors indicate static to dynamic changes in nucleation phase located at the source of detached wedge. The characteristics of seismic data distinguished debris flow and hitting obstacles from other seismic sources and allowed the estimations of debris flow speed. We analyzed and verified the seismic signals with field evidences to estimate the associated impacts and velocity of dynamic flow. The proximal high-quality seismic data allowed us to reconstruct the complete chronological sequence and evaluate impacts since the initiation of nucleation phase to its advancement. Furthermore, we suggest that real-time seismic monitoring with existing network and future deployment of integrated dense network can be used for forecasting of flow events and hazard mitigation in the downstream. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is a Gram-negative bacterium that causes chronic inflammations in the stomach area and is involved in ulcers, which can develop into gastric malignancies. H. pylori attaches and colonizes to the human epithelium using some of their outer membrane proteins (OMPs). HomB and HomA are the most studied OMPs from H. pylori as they play a crucial role in adherence, hyper biofilm formation, antibiotic resistance and are also associated with severe gastric malignancies. The role of HomA and HomB in pathogenesis concerning their structure and function has not been evaluated yet. In the present study, we explored the structural aspect of HomA and HomB proteins using various computational, biophysical and small-angle X-ray scattering (SAXS) techniques. Interestingly, the in-silico analysis revealed that HomA/B consists of 8 discontinuous N and C terminal β-strands forming a small β-barrel, along with a large surface-exposed globular domain. Further, biophysical experiments suggested that HomA and HomB are dimeric and most likely the cysteine residues present on surface-exposed loops participate in protein–protein interactions. Our study provides essential structural information of unexplored proteins of the Hom family that can help in a better understanding of H. pylori pathogenesis. [ABSTRACT FROM AUTHOR]

The nutritional challenge faced by the monogastric animals due to the chelation effects of phytic acid, fuel the research on bioprospecting of probiotics for phytase production. Pediococcus acidilactici SMVDUDB2 isolated from Kalarei, exhibited extracellular phytase activity of 5.583 U/mL after statistical optimization of fermentation conditions viz. peptone (1.27%); temperature (37 °C); pH (6.26) and maltose (1.43%). The phytase enzyme possessed optimum pH and temperature of 5.5 and 37 °C, respectively and was thermostable at 60 °C. The enzyme was purified 6.42 fold with a specific activity of 245.12 U/mg with hydrophobic interaction chromatography. The purified enzyme had Km and Vmax values of 0.385 mM and 4.965 μmol/min respectively, with sodium phytate as substrate. The strain depicted more than 80% survival rate at low pH (pH 2.0, 3.0), high bile salt concentration (0.3 and 0.5%), after gastrointestinal transit, highest hydrophobicity affinity with ethyl acetate (33.33 ± 0%), autoaggregation (77.68 ± 0.68%) as well as coaggregation (73.57 ± 0.47%) with Staphylococcus aureus (MTCC 3160). The strain exhibited antimicrobial activity against Bacillus subtilis (MTCC 121), Mycobacterium smegmatis (MTCC 994), Staphylococcus aureus (MTCC 3160), Proteus vulgaris (MTCC 426), Escherichia coli (MTCC 1652) and Lactobacillus rhamnosus (MTCC 1408). The amount of exopolysaccharide produced by the strain was 2 g/L. This strain having the capability of phytate degradation and possessing probiotic traits could find application in food and feed sectors. [ABSTRACT FROM AUTHOR]

The design and selection of ideal emitter discharge rates can be aided by accurate information regarding the wetted soil pattern under surface drip irrigation. The current field investigation was conducted in an apple orchard in SKUAST- Kashmir, Jammu and Kashmir, a Union Territory of India, during 2017–2019. The objective of the experiment was to examine the movement of moisture over time and assess the extent of wetting in both horizontal and vertical directions under point source drip irrigation with discharge rates of 2, 4, and 8 L h−1. At 30, 60, and 120 min since the beginning of irrigation, a soil pit was dug across the length of the wetted area on the surface in order to measure the wetting pattern. For measuring the soil moisture movement and wetted soil width and depth, three replicas of soil samples were collected according to the treatment and the average value were considered. As a result, 54 different experiments were conducted, resulting in the digging of pits [3 emitter discharge rates × 3 application times × 3 replications × 2 (after application and 24 after application)]. This study utilized the Drip-Irriwater model to evaluate and validate the accuracy of predictions of wetting fronts and soil moisture dynamics in both orientations. Results showed that the modeled values were very close to the actual field values, with a mean absolute error of 0.018, a mean bias error of 0.0005, a mean absolute percentage error of 7.3, a root mean square error of 0.023, a Pearson coefficient of 0.951, a coefficient of correlation of 0.918, and a Nash–Sutcliffe model efficiency coefficient of 0.887. The wetted width just after irrigation was measured at 14.65, 16.65, and 20.62 cm; 16.20, 20.25, and 23.90 cm; and 20.00, 24.50, and 28.81 cm in 2, 4, and 8 L h−1, at 30, 60, and 120 min, respectively, while the wetted depth was observed 13.10, 16.20, and 20.44 cm; 15.10, 21.50, and 26.00 cm; 19.40, 25.00, and 31.00 cm, respectively. As the flow rate from the emitter increased, the amount of moisture dissemination grew (both immediately and 24 h after irrigation). The soil moisture contents were observed 0.4300, 0.3808, 0.2298, 0.1604, and 0.1600 cm3 cm−3 just after irrigation in 2 L h−1 while 0.4300, 0.3841, 0.2385, 0.1607, and 0.1600 cm3 cm−3 were in 4 L h−1 and 0.4300, 0.3852, 0.2417, 0.1608, and 0.1600 cm3 cm−3 were in 8 L h−1 at 5, 10, 15, 20, and 25 cm soil depth in 30 min of application time. Similar distinct increments were found in 60, and 120 min of irrigation. The findings suggest that this simple model, which only requires soil, irrigation, and simulation parameters, is a valuable and practical tool for irrigation design. It provides information on soil wetting patterns and soil moisture distribution under a single emitter, which is important for effectively planning and designing a drip irrigation system. Investigating soil wetting patterns and moisture redistribution in the soil profile under point source drip irrigation helps promote efficient planning and design of a drip irrigation system. [ABSTRACT FROM AUTHOR]

The present work focuses on the dynamical aspects of cross-reactivity between myelin based protein (MBP) self-peptide and two microbial peptides (UL15, PMM) for Hy.1B11 T-cell receptor (TCR). This same TCR was isolated from a patient suffering from multiple sclerosis (MS). The study aims at highlighting the chemical interactions underlying recognition mechanisms between TCR and the peptides presented by Major Histocompatibility Complex (MHC) proteins, which form a crucial component in adaptive immune response against foreign antigens. Since the ability of a TCR to recognize different peptide antigens presented by MHC depends on its cross-reactivity, we used molecular dynamics methods to obtain atomistic detail on TCR-peptide-MHC complexes. Our results show how the dynamical basis of Hy.1B11 TCR's cross-reactivity is rooted in a similar bridging interaction pattern across the TCR-peptide-MHC interface. Our simulations confirm the importance of TCR CDR3α E98 residue interaction with MHC and a predominant role of P6 peptide residue in MHC binding affinity. Altogether, our study provides energetic and dynamical insights into factors governing peptide recognition by the cross-reactive Hy.1B11 TCR, found in MS patient. [ABSTRACT FROM AUTHOR]

Molecular chaperones are essential molecules for cell growth, whereby they maintain protein homeostasis. Because of their central cellular function, bacterial chaperones might be potential candidates for drug targets. Antimicrobial resistance is currently one of the greatest threats to human health, with gram-negative bacteria being of major concern. We found that a Cu2+ complex readily crosses the bacterial cell wall and inhibits SlyD, which is a molecular chaperone, cis/trans peptidyl prolyl isomerise (PPIase) and involved in various other metabolic pathways. The Cu2+ complex binds to the active sites of SlyD, which suppresses its PPIase and chaperone activities. Significant cell growth retardation could be observed for pathogenic bacteria (e.g., Staphylococcus aureus and Pseudomonas aeruginosa). We anticipate that rational development of drugs targeting molecular chaperones might help in future control of pathogenic bacterial growth, in an era of rapidly increasing antibiotic resistance. [ABSTRACT FROM AUTHOR]

To become clinically effective, antimicrobial peptides (AMPs) should be non-cytotoxic to host cells. Piscidins are a group of fish-derived AMPs with potent antimicrobial and antiendotoxin activities but limited by extreme cytotoxicity. We conjectured that introduction of cationic residue(s) at the interface of polar and non-polar faces of piscidins may control their insertion into hydrophobic mammalian cell membrane and thereby reducing cytotoxicity. We have designed several novel analogs of piscidin-1 by substituting threonine residue(s) with L and D-lysine residue(s). L/D-lysine-substituted analogs showed significantly reduced cytotoxicity but exhibited either higher or comparable antibacterial activity akin to piscidin-1. Piscidin-1-analogs demonstrated higher efficacy than piscidin-1 in inhibiting lipopolysaccharide (LPS)-induced pro-inflammatory responses in THP-1 cells. T15,21K-piscidin-1 (0.5 mg/Kg) and T15,21dK-piscidin-1 (1.0 mg/Kg) demonstrated 100% survival of LPS (12.0 mg/Kg)-administered mice. High resolution NMR studies revealed that both piscidin-1 and T15,21K-piscidin-1 adopted helical structures, with latter showing a shorter helix, higher amphipathicity and cationic residues placed at optimal distances to form ionic/hydrogen bond with lipid A of LPS. Remarkably, T15,21dK-piscidin-1 showed a helix-loop-helix structure in LPS and its interactions with LPS could be sustained by the distance of separation of side chains of R7 and D-Lys-15 which is close to the inter-phosphate distance of lipid A. [ABSTRACT FROM AUTHOR]

A latent viral reservoir that resides in resting CD4+ T cells represents a major barrier for eradication of HIV infection. We test here the impact of HIV protease inhibitor (PI) based combination anti-retroviral therapy (cART) over nonnucleoside reverse transcriptase inhibitor (NNRTI)-based cART on HIV-1 reactivation and integration in resting CD4+ T cells. This is a prospective cohort study of patients with chronic HIV-1 infection treated with conventional cART with an undetectable viremia. We performed a seven-year study of 47 patients with chronic HIV-infection treated with cART regimens and with undetectable plasma HIV-1 RNA levels for at least 1 year. Of these 47 patients treated with cART, 24 were treated with a PI-based regimen and 23 with a NNRTI-based regimen as their most recent treatment for more than one year. We evaluated the HIV-1 reservoir using reactivation assay and integrated HIV-1 DNA, respectively, in resting CD4+ T cells. Resting CD4+ T cells isolated from PI-treated patients compared to NNRTI-treated patients showed a limited HIV-1 reactivation upon T-cell stimulation (p = 0·024) and a lower level of HIV-1 integration (p = 0·024). Our study indicates that PI-based cART could be more efficient than NNRTI-based cART for limiting HIV-1 reactivation in aviremic chronically infected patients. [ABSTRACT FROM AUTHOR]

Nitrous-oxide emission and nitrate addition from agriculture to earth's environment are two main agriculture related anthropogenic causes of environmental degradation that needs greater attention. For addressing the aforesaid issue, new techniques/practices need to be developed and implemented. The present investigation, which was focused on this issue, resulted in developing a new mode of nitrogen (N) placement, i.e. 'mid rib placement upper to corms in two splits (MRPU-2S)', that could reduce nitrous oxide N emission by around 70.11% and, nitrate N leaching and runoff by around 68.26 and 67.09%, respectively, over conventional method, in saffron growing soils of northwest Himalayas. Besides plummeting environmental degradation, MRPU-2S further resulted in enhancing saffron yield by 33.33% over conventional method. The findings of the present investigation were used to develop new empirical models for predicting saffron yield, nitrate N leaching and nitrous-oxide N emission. The threshold limits of nitrate N leaching and nitrous oxide N emission have also been reported exclusively in the present study. [ABSTRACT FROM AUTHOR]

This paper explores gold nanoparticle (GNP) modified copper oxide nanowires(CuO NWs)based electrode grown on copper foil for non-enzymatic glucose detection in a wide linear ranging up to 31.06 mM, and 44.36 mM at 0.5 M NaOH and 1 M NaOH concentrations. The proposed electrode can be used to detect a very low glucose concentration of 0.3 µM with a high linearity range of 44.36mM and sensitivity of 1591.44 µA mM−1 cm−2. The electrode is fabricated by first synthesizing Cu (OH)2 NWs on a copper foil by chemical etching method and then heat treatment is performed to convert Cu (OH)2 NWs into CuO NWs. The GNPs are deposited on CuO NWs to enhance the effective surface-to-volume ratio of the electrode with improved catalytic activity. The surface morphology has been investigated by XRD, XPS, FE-SEM and HR-TEM analysis. The proposed sensor is expected to detect low-level of glucose in urine, and saliva. At the same time, it can also be used to measure extremely high sugar levels (i.e. hyperglycemia) of ~ 806.5454 mg/dl. The proposed sensor is also capable of detecting glucose after multiple bending of the GNP modified CuO NWs electrode. The proposed device is also used to detect the blood sugar level in human being and it is found that this sensor's result is highly accurate and reliable. [ABSTRACT FROM AUTHOR]

Cytokines of the interleukin (IL)-1 family regulate immune and inflammatory responses. The recently discovered IL-36 family members are involved in psoriasis, rheumatoid arthritis, and pulmonary diseases. Here, we show that IL-36α interacts with heme thereby contributing to its regulation. Based on in-depth spectroscopic analyses, we describe two heme-binding sites in IL-36α that associate with heme in a pentacoordinated fashion. Solution NMR analysis reveals structural features of IL-36α and its complex with heme. Structural investigation of a truncated IL-36α supports the notion that the N-terminus is necessary for association with its cognate receptor. Consistent with our structural studies, IL-36-mediated signal transduction was negatively regulated by heme in synovial fibroblast-like synoviocytes from rheumatoid arthritis patients. Taken together, our results provide a structural framework for heme-binding proteins and add IL-1 cytokines to the group of potentially heme-regulated proteins. [ABSTRACT FROM AUTHOR]

Pesticides residue poses serious concerns to human health. The present study was carried out to determine the pesticide residues of peri-urban bovine milk (n = 1183) from five different sites (Bangalore, Bhubaneswar, Guwahati, Ludhiana and Udaipur) in India and dietary exposure risk assessment to adults and children. Pesticide residues were estimated using gas chromatography with flame thermionic and electron capture detectors followed by confirmation on gas chromatography-mass spectrometer. The results noticed the contamination of milk with hexachlorocyclohexane (HCH), dichloro-diphenyl trichloroethane (DDT), endosulfan, cypermethrin, cyhalothrin, permethrin, chlorpyrifos, ethion and profenophos pesticides. The residue levels in some of the milk samples were observed to be higher than the respective maximum residue limits (MRLs) for pesticide. Milk samples contamination was found highest in Bhubaneswar (11.2%) followed by Bangalore (9.3%), Ludhiana (6.9%), Udaipur (6.4%) and Guwahati (6.3%). The dietary risk assessment of pesticides under two scenarios i.e. lower-bound scenario (LB) and upper-bound (UB) revealed that daily intake of pesticides was substantially below the prescribed acceptable daily intake except for fipronil in children at UB. The non-cancer risk by estimation of hazard index (HI) was found to be below the target value of one in adults at all five sites in India. However, for children at the UB level, the HI for lindane, DDT and ethion exceeded the value of one in Ludhiana and Udaipur. Cancer risk for adults was found to be in the recommended range of United States environment protection agency (USEPA), while it exceeded the USEPA values for children. [ABSTRACT FROM AUTHOR]

In 2017–2019 a surge of Shispare Glacier, a former tributary of the once larger Hasanabad Glacier (Hunza region), dammed the proglacial river of Muchuhar Glacier, which formed an ice-dammed lake and generated a small Glacial Lake Outburst Flood (GLOF). Surge movement produced the highest recorded Karakoram glacier surface flow rate using feature tracking (~18 ± 0.5 m d−1) and resulted in a glacier frontal advance of 1495 ± 47 m. The surge speed was less than reports of earlier Hasanabad advances during 1892/93 (9.3 km) and 1903 (9.7 km). Surges also occurred in 1973 and 2000–2001. Recent surges and lake evolution are examined using feature tracking in satellite images (1990–2019), DEM differencing (1973–2019), and thermal satellite data (2000–2019). The recent active phase of Shispare surge began in April 2018, showed two surface flow maxima in June 2018 and May 2019, and terminated following a GLOF on 22–23 June 2019. The surge likely had hydrological controls influenced in winter by compromised subglacial flow and low meltwater production. It terminated during summer probably because increased meltwater restored efficient channelized flow. We also identify considerable heterogeneity of movement, including spring/summer accelerations. [ABSTRACT FROM AUTHOR]

Arsenic (As) contamination of water is a global concern and rice consumption is the biggest dietary exposure to human posing carcinogenic risks, predominantly in Asia. Sulfur (S) is involved in di-sulfide linkage in many proteins and plays crucial role in As detoxification. Present study explores role of variable S supply on rice leaf proteome, its inclination towards amino acids (AA) profile and non protein thiols under arsenite exposure. Analysis of 282 detected proteins on 2-DE gel revealed 113 differentially expressed proteins, out of which 80 were identified by MALDI-TOF-TOF. The identified proteins were mostly involved in glycolysis, TCA cycle, AA biosynthesis, photosynthesis, protein metabolism, stress and energy metabolism. Among these, glycolytic enzymes play a major role in AA biosynthesis that leads to change in AAs profiling. Proteins of glycolytic pathway, photosynthesis and energy metabolism were also validated by western blot analysis. Conclusively S supplementation reduced the As accumulation in shoot positively skewed thiol metabolism and glycolysis towards AA accumulation under AsIII stress. [ABSTRACT FROM AUTHOR]

Bias-induced oxygen ion dynamics underpins a broad spectrum of electroresistive and memristive phenomena in oxide materials. Although widely studied by device-level and local voltage-current spectroscopies, the relationship between electroresistive phenomena, local electrochemical behaviors, and microstructures remains elusive. Here, the interplay between history-dependent electronic transport and electrochemical phenomena in a NiO single crystalline thin film with a number of well-defined defect types is explored on the nanometer scale using an atomic force microscopy-based technique. A variety of electrochemically-active regions were observed and spatially resolved relationship between the electronic and electrochemical phenomena was revealed. The regions with pronounced electroresistive activity were further correlated with defects identified by scanning transmission electron microscopy. Using fully coupled mechanical-electrochemical modeling, we illustrate that the spatial distribution of strain plays an important role in electrochemical and electroresistive phenomena. These studies illustrate an approach for simultaneous mapping of the electronic and ionic transport on a single defective structure level such as dislocations or interfaces, and pave the way for creating libraries of defect-specific electrochemical responses. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Several G-quadruplex forming motifs have been reported to be highly conserved in the regulatory regions of the genome of different organisms and influence various biological processes like DNA replication, recombination and gene expression. Here, we report the highly conserved and three potentially G-quadruplex forming motifs (SP-PGQs) in the essential genes (hsdS, recD, and pmrA) of the Streptococcus pneumoniae genome. These genes were previously observed to play a vital role in providing the virulence to the bacteria, by participating in the host-pathogen interaction, drug-efflux system and recombination- repair system. However, the presence and importance of highly conserved G-quadruplex motifs in these genes have not been previously recognized. We employed the CD spectroscopy, NMR spectroscopy, and electrophoretic mobility shift assay to confirm the adaptation of the G-quadruplex structure by the SP-PGQs. Further, ITC and CD melting analysis revealed the energetically favorable and thermodynamically stable interaction between a candidate G4 binding small molecule TMPyP4 and SP-PGQs. Next, TFP reporter based assay confirmed the regulatory role of SP-PGQs in the expression of PGQ harboring genes. All these experiments together characterized the SP-PGQs as a promising drug target site for combating the Streptococcus pneumoniae infection. [ABSTRACT FROM AUTHOR]

Piperine, a naturally occurring alkaloid, is well known as anti-oxidant, anti-mutagenic, anti-tumor and anti-proliferative agent. Piperine exerts such pharmacological activities by binding or interacting with various cellular targets. Recently, the first report for Piperine interaction with duplex DNA has been published last year but its interaction with G-quadruplex structures has not been studied yet. Herein, we report for the first time the interaction of Piperine with various DNA G-quadruplex structures. Comprehensive biophysical techniques were employed to determine the basis of interaction for the complex formed between Piperine and G-quadruplex DNA sequences. Piperine showed specificity for G-quadruplex DNA over double stranded DNA, with highest affinity for G-quadruplex structure formed at c-myc promoter region. Further, in-vitro studies show that Piperine causes apoptosis-mediated cell death that further emphasizes the potential of this natural product, Piperine, as a promising candidate for targeting G-quadruplex structure and thus, acts as a potent anti-cancer agent. [ABSTRACT FROM AUTHOR]

Nucleic acid G-quadruplex structure (G4) Interacting Proteins DataBase (G4IPDB) is an important database that contains detailed information about proteins interacting with nucleic acids that forms G-quadruplex structures. G4IPDB is the first database that provides comprehensive information about this interaction at a single platform. This database contains more than 200 entries with details of interaction such as interacting protein name and their synonyms, their UniProt-ID, source organism, target name and its sequences, ∆Tm, binding/dissociation constants, protein gene name, protein FASTA sequence, interacting residue in protein, related PDB entries, interaction ID, graphical view, PMID, author's name and techniques that were used to detect their interactions. G4IPDB also provides an efficient web-based 'G-quadruplex predictor tool' that searches putative G-quadruplex forming sequences simultaneously in both sense and anti-sense strands of the query nucleotide sequence and provides the predicted G score. Studying the interaction between proteins and nucleic acids forming G-quadruplex structures could be of therapeutic significance for various diseases including cancer and neurological disease, therefore, having detail information about their interactions on a single platform would be helpful for the discovery and development of novel therapeutics. G4IPDB can be routinely updated (twice in year) and freely available on http://bsbe.iiti.ac.in/bsbe/ipdb/index.php. [ABSTRACT FROM AUTHOR]

A severe bottleneck exists during HIV-1 mucosal transmission. However, viral properties that determine HIV-1 transmissibility are not fully elucidated. We identified multiple transmitted/founder (T/F) viruses in six HIV-1-infected subjects by analyzing whole genome sequences. Comparison of biological phenotypes of different T/F viruses from the same individual allowed us to more precisely identify critical determinants for viral transmissibility since they were transmitted under similar conditions. All T/F viruses used coreceptor CCR5, while no T/F viruses used CXCR4 or GPR15. However, the efficiency for different T/F viruses from the same individual to use CCR5 was significantly variable, and the differences were even more significant for usage of coreceptors FPRL1, CCR3 and APJ. Resistance to IFN-α was also different between T/F viruses in 2 of 3 individuals. The relative fitness between T/F viruses from the same subject was highly variable (2-6%). Importantly, the levels of coreceptor usage efficiency, resistance to IFN-α and viral fitness were not associated with proportions of T/F viruses in each individual during acute infection. Our results show that the modest but significant differences in coreceptor usage efficiency, IFN-α sensitivity and viral fitness each alone may not play a critical role in HIV-1 transmission. [ABSTRACT FROM AUTHOR]

Granulocyte colony stimulating factor (G-CSF) may enhance recovery from stroke through neuroprotective mechanisms if administered early, or neurorepair if given later. Several small trials suggest administration is safe but effects on efficacy are unclear. We searched for randomised controlled trials (RCT) assessing G-CSF in patients with hyperacute, acute, subacute or chronic stroke, and asked Investigators to share individual patient data on baseline characteristics, stroke severity and type, end-of-trial modified Rankin Scale (mRS), Barthel Index, haematological parameters, serious adverse events and death. Multiple variable analyses were adjusted for age, sex, baseline severity and time-to-treatment. Individual patient data were obtained for 6 of 10 RCTs comprising 196 stroke patients (116 G-CSF, 80 placebo), mean age 67.1 (SD 12.9), 92% ischaemic, median NIHSS 10 (IQR 5-15), randomised 11 days (interquartile range IQR 4-238) post ictus; data from three commercial trials were not shared. G-CSF did not improve mRS (ordinal regression), odds ratio OR 1.12 (95% confidence interval 0.64 to 1.96, p = 0.62). There were more patients with a serious adverse event in the G-CSF group (29.6% versus 7.5%, p = 0.07) with no significant difference in all-cause mortality (G-CSF 11.2%, placebo 7.6%, p = 0.4). Overall, G-CSF did not improve stroke outcome in this individual patient data meta-analysis. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) patients are at higher risk of developing lung cancer and its metastasis, but no suitable biomarker has been reported for differential diagnosis of these patients. Levels of serum biomarkers (VEGF, IL-8, MMP-9 and MMP-2) were analyzed in these patients, which were compared with healthy donors (HD). Levels of VEGF (P < 0.005) and MMP-9 (P < 0.05) were significantly higher in COPD patients than HD. Compared to HD, a decrease in IL-8 (~8.1 folds; P < 0.0001) but an increase in MMP-9 (~1.6 folds; P < 0.05) levels were observed in the lung cancer patients. Cancer patients showed significantly (P < 0.005) lower levels of serum VEGF (1.9 folds) and IL-8 (~9 folds) than the COPD patients. VEGF level was significantly higher (2.6 folds; P < 0.0005) in metastatic than non-metastatic cancer patients. However, MMP-2 didn't show significant variation in these patients. The Youden's index (YI) values for lung cancer diagnosis in HD using IL-8 was 0.55 with 83.3% overall accuracy. VEGF was able to diagnose COPD in HD with better YI (0.38) and overall accuracy (70.6%). IL-8 was able to diagnose cancer in COPD patients and HD with YI values of 0.35, 0.55 with 71% and 83.3% overall accuracy, respectively. [ABSTRACT FROM AUTHOR]