HSMotifDiscover: identification of motifs in sequences composed of non-single-letter elements.

SUMMARY: The functional sub-string(s) of a biopolymer sequence defines the specificity of its interaction with other biomolecules and is often referred to as motifs. Computational algorithms and software have been broadly developed for finding such motifs in sequences in which the individual elements are single characters, such as those in DNA and protein sequences. However, there are more complex scenarios where the motifs exist in non-single-letter contexts, e.g. preferred patterns of chemical modifications on proteins, DNAs, RNAs or polysaccharides. To search for those motifs, we describe a new method that converts the modified sequence elements to representative single-letter codes and then uses a modified Gibbs-sampling algorithm to define the position specific scoring matrix representing the motif(s). As a proof of principle, we describe the implementation and application of an R package for discovering heparan sulfate (HS) motifs in glycan sequences, which are important in regulating protein-protein interactions. This software can be valuable for analyzing high-throughput glycoprotein binding data using microarrays with HS oligosaccharides or other biological polymers. AVAILABILITY AND IMPLEMENTATION: HSMotifDiscover is freely available as an open source R package released under an MIT license at https://github.com/bioinfoDZ/HSMotifDiscover and also available in the form of an app at https://hsmotifdiscover.shinyapps.io/HSMotifDiscover_ShinyApp/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Plant Nutrition: An Effective Way to Alleviate Abiotic Stress in Agricultural Crops.

By the year 2050, the world's population is predicted to have grown to around 9-10 billion people. The food demand in many countries continues to increase with population growth. Various abiotic stresses such as temperature, soil salinity and moisture all have an impact on plant growth and development at all levels of plant growth, including the overall plant, tissue cell, and even sub-cellular level. These abiotic stresses directly harm plants by causing protein denaturation and aggregation as well as increased fluidity of membrane lipids. In addition to direct effects, indirect damage also includes protein synthesis inhibition, protein breakdown, and membranous loss in chloroplasts and mitochondria. Abiotic stress during the reproductive stage results in flower drop, pollen sterility, pollen tube deformation, ovule abortion, and reduced yield. Plant nutrition is one of the most effective ways of reducing abiotic stress in agricultural crops. In this paper, we have discussed the effectiveness of different nutrients for alleviating abiotic stress. The roles of primary nutrients (nitrogen, phosphorous and potassium), secondary nutrients (calcium, magnesium and sulphur), micronutrients (zinc, boron, iron and copper), and beneficial nutrients (cobalt, selenium and silicon) in alleviating abiotic stress in crop plants are discussed.

Reply to Letter to the Editor: A Fatal Case of Acute Disseminated Encephalomyelitis-A Diagnosis to Ponder in Pandemic.

How to cite this article: Kumar A, Sabharwal P, Gupta P, Singh VK, Rao BK. Reply to Letter to the Editor: A Fatal Case of Acute Disseminated Encephalomyelitis-A Diagnosis to Ponder in Pandemic. Indian J Crit Care Med 2022;26(9):1062.

Stereo3D: using stereo images to enrich 3D visualization.

SUMMARY: Visualization in 3D space is a standard but critical process for examining the complex structure of high-dimensional data. Stereoscopic imaging technology can be adopted to enhance 3D representation of many complex data, especially those consisting of points and lines. We illustrate the simple steps that are involved and strongly recommend others to implement it in designing visualization software. To facilitate its application, we created a new software that can convert a regular 3D scatterplot or network figure to a pair of stereo images. AVAILABILITY AND IMPLEMENTATION: Stereo3D is freely available as an open source R package released under an MIT license at https://github.com/bioinfoDZ/Stereo3D. Others can integrate the codes and implement the method in academic software. CONTACT: deyou.zheng@einsteinmed.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Analysis of a highly sensitive side polished hollow fiber plasmonic sensor and its application as a magnetometer.

A highly sensitive hollow fiber (HF) sensor based on surface plasmon resonance is proposed and analyzed numerically. The sensor design involves a side polished HF with a nanoscale gold film deposited over the polished surface and an analyte filled core. The hollow portion of the fiber serves simultaneously as an analyte channel and core, when filled with high refractive index liquid. By analyzing the modal characteristics of the sensor using the finite element method, it is found that the wavelength sensitivity of the HF sensor varies from 25,642 nm/RIU (refractive index unit) to 60,000 nm/RIU in the range 1.45 to 1.47 RIU along with highest amplitude sensitivity of ${4231.7}\,\,{{\rm RIU}^{-1}}$4231.7RIU-1. The minimum measurable alteration by the sensor lies in the order of ${{10}^{-6}}\,\,{\rm RIU}$10-6RIU. The sensor also exhibits a high value of figure of merit (FOM) up to ${976}\,\,{{\rm RIU}^{-1}}$976RIU-1 representing a very good overall performance. Moreover, due to the feasibility of design, the specific application of the sensor to magnetic field sensing is also demonstrated and achieved maximum sensitivity of 1361 pm/Oe.

Analysis of a highly sensitive flat fiber plasmonic refractive index sensor.

In this paper, we propose an efficient double-layered flat fiber (DLFF) plasmonic refractive index sensor having high resolution and linearity. Thin gold film is used as surface plasmon resonance (SPR) active material protected by a titanium dioxide layer, both deposited on the upper flat surface of DLFF. The sensor consists of an analyte channel in the central core hole as well as on the top of the fiber. Structural parameters of DLFF and thickness of gold and titanium dioxide layer are analyzed based on the finite element method. The optimized structure is studied based on wavelength and amplitude interrogation techniques in the near-infrared region. Numerical results show average wavelength sensitivity of 12172 nm/RIU with a resolution of 8.21×10-6RIU (refractive index unit) in the highly refractive index (RI) range from 1.445 to 1.490. Further, amplitude sensitivity of this probe is found to be 2910RIU-1 with a resolution of 3.44×10-6RIU, which is the highest among all reported PCF SPR sensors, as per the authors' best knowledge. Compared with traditional photonic crystal fiber, the designed DLFF makes the sensor configuration simple to fabricate as well as a potential candidate for developing biochemical sensors and portable devices.

Classification of pathogenic microbes using a minimal set of single nucleotide polymorphisms derived from whole genome sequences.

In a context specific manner, Intra-species genomic variation plays an important role in phenotypic diversity observed among pathogenic microbes. Efficient classification of these pathogens is important for diagnosis and treatment of several infectious diseases. NGS technologies have provided access to wealth of data that can be utilized to discover important markers for pathogen classification. In this paper, we described three different approaches (Jensen-Shannon divergence, random forest and Shewhart control chart) for identification of a minimal set of SNPs that can be used for classification of organisms. These methods are generic and can be implemented for analysis of any organism. We have shown usefulness of these approaches for analysis of Mycobacterium tuberculosis and Escherichia coli isolates. We were able to identify a minimal set of 18 SNPs that can be used as molecular markers for phylogroup based classification and 8 SNPs for pathogroup based classification of E. coli.

Prospects of Photonic Crystal Fiber as Physical Sensor: An Overview.

Photonic crystal fiber sensors have potential application in environmental monitoring, industry, biomedicine, food preservation, and many more. These sensors work based on advanced and flexible phototonic crystal fiber (PCF) structures, controlled light propagation for the measurement of amplitude, phase, polarization and wavelength of spectrum, and PCF-incorporated interferometry techniques. In this article various PCF-based physical sensors are summarized with the advancement of time based on reported works. Some physical PCF sensors are discussed based on solid core as well as hollow core structures, dual core fibers, liquid infiltrated structures, metal coated fibers, grating incorporated fibers. With the advancement of sensing technology the possibilities of temperature, pressure, strain, twist, curvature, electromagnetic field, and refractive index sensing are discussed. Also, limitations as well as possible solutions and future hopes are outlined.

Classical swine fever in India: current status and future perspective.

Classical swine fever (CSF) is a globally significant disease of swine caused by classical swine fever virus. The virus affects the wild boars and pigs of all age groups, leading to acute, chronic, late-onset or in-apparent course of the disease. The disease causes great economic loss to the piggery industry due to mortality, stunted growth, poor reproductive performance, and by impeding the international trade of pig and pig products. In India, CSF outbreaks are reported from most of the states wherever pig rearing is practiced and more frequently from northeast states. In spite of the highly devastating nature and frequent outbreaks, CSF remained underestimated and neglected for decades in India. The country requires rapid and sensitive diagnostic tests for an early detection of infection to limit the spread of the disease. Also, effective prophylactics are required to help in control and eradication of the disease for the development of the piggery industry. This review looks into the economic impact; epidemiology of CSF highlighting the temporal and spatial occurrence of outbreaks in the last two decades, circulation, and emergence of the virus genotypes in and around the country; and the constraints in the disease control, with the aim to update the knowledge of current status of the disease in India. The article also emphasizes the importance of the disease and the need to develop rapid specific diagnostics and effective measures to eradicate the disease.

Acute right heart syndrome: Rescue treatment with inhaled nitric oxide.

Acute right heart syndrome is a common occurrence in intensive care units and is associated with a poor prognosis. There is lack of understanding of the involved pathophysiology, standard diagnostic protocols and treatment guidelines. Management goals include ensuring adequate right ventricle (RV) filling, maximizing RV contraction and reducing RV afterload. We describe a 39-year-old female with acute decompensated right heart failure secondary to multiple causes. She was managed with inhaled nitric oxide. Her condition improved, which was evident by a decrease in her pulmonary artery systolic pressure on serial echocardiography, decreased requirement of vasopressors and successful weaning from the ventilator.

Severe suicidal digoxin and propranolol toxicity with insulin overdose.

We present a case of a 32-year-old male doctor, with type I diabetes mellitus on daily insulin therapy, who allegedly consumed large doses of digoxin and propranolol along with simultaneous administration of large dose of insulin with suicidal intent. Initial investigations revealed serum digoxin levels of 7.5 ng/ml, serum insulin 500 µIU/ml, and serum C-peptide 0.43 ng/ml. He was managed with charcoal-based hemoperfusion for digoxin overdose along with injection glucagon for propranolol overdose. His blood sugar levels were maintained with continuous infusion of 20% dextrose till the patient was allowed to take oral diet. Significant clinical improvement was noticed with this therapy which was evident by progressively declining serum digoxin levels, normalization of pulse rate, and adequate blood glucose levels. Finally, with a good hemodynamic profile and a serum digoxin level well within normal limits, he was discharged following consultation with a psychiatrist.

Complete genome sequence of S-type Mycobacterium avium subsp. paratuberculosis isolated from an organized goat herd in India.

The present report communicates the first complete genome sequence of S-type Mycobacterium avium subsp. paratuberculosis, isolated from an organised goat herd in Uttar Pradesh, India. Bacteria were isolated in pure culture on Herrold's egg yolk medium (HEYM) slants containing mycobactin J from the faecal sample collected per-rectally from a clinical diseased goat, and next-generation sequencing (NGS) revealed that the genome sequence length of the isolated strain named MAP-Gt-9 is 4,509,428 bp with no plasmid DNA, with a GC content of 69.5%, an N50 value of 125,474 bp, and an L50 value of 12, containing 4235 coding DNA sequences (CDSs), 44 tRNAs, 3 ncRNAs and 1 each 5S, 16S, 23S rRNA genes.

Quantitative measurement of retinal nerve fiber layer thickness and its correlation with optical coherence tomography angiography vascular biomarker changes in preclinical diabetic retinopathy.

PURPOSE: The present study was done to assess the use of optical coherence tomography angiography (OCTA) in detecting earlier stages of diabetic retinopathy and for the early management and effective blood glucose control in preclinical diabetic patients for preventing retinal nerve fiber layer (RNFL) thinning. METHODS: A tertiary care center-based prospective observational study was conducted from the year 2021 to 2022 in the Department of Ophthalmology. The study included 50 cases and 50 controls. The parameters analyzed by using OCTA (Topcon 3D OCT-1 Maestro2) were RNFL thickness and peripapillary vessel density. RESULTS: We found that the RNFL thickness in the temporal and superior disc in patients with preclinical diabetic retinopathy was significantly (0.041 and 0.044, respectively) decreased. The duration of diabetes and glycated hemoglobin (HbA1c) were the risk factors for peripapillary vessel density reduction in patients with preclinical diabetic retinopathy (P < 0.001). CONCLUSION: RNFL thinning is an early sign of retinal neurodegeneration and is associated with peripapillary vessel density reduction. Early management and effective blood glucose control in diabetes patients may be beneficial for preventing RNFL thinning in superior and temporal disc.

System of wheat intensification (SWI): Effects on lodging resistance, photosynthetic efficiency, soil biomes, and water productivity.

Intense cultivation with narrow row spacing in wheat, a common practice in the Indo-Gangetic plains of South Asia, renders the crop more susceptible to lodging during physiological maturity. This susceptibility, compounded by the use of traditional crop cultivars, has led to a substantial decline in overall crop productivity. In response to these challenges, a two-year field study on the system of wheat intensification (SWI) was conducted. The study involved three different cultivation methods in horizontal plots and four wheat genotypes in vertical plots, organized in a strip plot design. Our results exhibited that adoption of SWI at 20 cm × 20 cm resulted in significantly higher intercellular CO2 concentration (5.9-6.3%), transpiration rate (13.2-15.8%), stomatal conductance (55-59%), net photosynthetic rate (126-160%), and photosynthetically active radiation (PAR) interception (1.6-25.2%) over the existing conventional method (plant geometry 22.5 cm × continuous plant to plant spacing) of wheat cultivation. The lodging resistance capacity of both the lower and upper 3rd nodes was significantly higher in the SWI compared to other cultivation methods. Among different genotypes, HD 2967 demonstrated the highest recorded value for lodging resistance capacity, followed by HD 2851, HD 3086, and HD 2894. In addition, adoption of the SWI at 20 cm × 20 cm enhanced crop grain yield by 36.9-41.6%, and biological yield by 27.5-29.8%. Significantly higher soil dehydrogenase activity (12.06 µg TPF g-1 soil hr-1), arylsulfatase activity (82.8 µg p-nitro phenol g-1 soil hr-1), alkaline phosphatase activity (3.11 n moles ethylene g-1 soil hr-1), total polysaccharides, soil microbial biomass carbon, and soil chlorophyll content were also noted under SWI over conventional method of the production. Further, increased root volumes, surface root density and higher NPK uptake were recorded under SWI at 20×20 cm in comparison to rest of the treatments. Among the tested wheat genotypes, HD-2967 and HD-3086 had demonstrated notable increases in grain and biological yields, as well as improvements in the photosynthetically active radiation (PAR) and chlorophyll content. Therefore, adoption of SWI at 20 cm ×20 cm (square planting) with cultivars HD 2967 might be the best strategy for enhancing crop productivity and resource-use efficiency under the similar wheat growing conditions of India and similar agro-ecotypes of the globe.

Changes in microbial community structure and yield responses with the use of nano-fertilizers of nitrogen and zinc in wheat-maize system.

The growing popularity of nano-fertilization around the world for enhancing yield and nutrient use efficiency has been realized, however its influence on soil microbial structure is not fully understood. The purpose of carrying out this study was to assess the combined effect of nano and conventional fertilizers on the soil biological indicators and crop yield in a wheat-maize system. The results indicate that the at par grain yield of wheat and maize was obtained with application of 75% of recommended nitrogen (N) with full dose of phosphorus (P) and potassium (K) through conventional fertilizers along with nano-N (nano-urea) or nano-N plus nano-Zn sprays and N100PK i.e. business as usual (recommended dose of fertilizer). Important soil microbial property like microbial biomass carbon was found statistically similar with nano fertilizer-based management (N75PK + nano-N, and N75PK + nano-N + nano-Zn) and conventional management (N100PK), during both wheat and maize seasons. The experimental data indicated that the application of foliar spray of nano-fertilizers along with 75% N as basal is a sustainable nutrient management approach with respect to growth, yield and rhizosphere biological activity. Furthermore, two foliar sprays of nano-N or nano-N + nano-Zn curtailed N requirement by 25%, furthermore enhanced soil microbial diversity and the microbial community structure. The specific microbial groups, including Actinobacteria, Bacteroidia, and Proteobacteria, were present in abundance and were positively correlated with wheat and maize yield and soil microbial biomass carbon. Thus, one of the best nutrient management approaches for sustaining productivity and maintaining sound microbial diversity in wheat-maize rotation is the combined use of nano-fertilizers and conventional fertilizers.

Mismatch repair protein MLH1 suppresses replicative stress in BRCA2-deficient breast tumors.

Loss of BRCA2 (breast cancer 2) is lethal for normal cells. Yet it remains poorly understood how, in BRCA2 mutation carriers, cells undergoing loss of heterozygosity overcome the lethality and undergo tissue-specific neoplastic transformation. Here, we identified mismatch repair gene mutL homolog 1 (MLH1) as a genetic interactor of BRCA2 whose overexpression supports the viability of Brca2-null cells. Mechanistically, we showed that MLH1 interacts with Flap endonuclease 1 (FEN1) and competes to process the RNA flaps of Okazaki fragments. Together, they restrained the DNA2 nuclease activity on the reversed forks of lagging strands, leading to replication fork (RF) stability in BRCA2-deficient cells. In these cells, MLH1 also attenuated R-loops, allowing the progression of stable RFs, which suppressed genomic instability and supported cell viability. We demonstrated the significance of their genetic interaction by the lethality of Brca2-mutant mice and inhibition of Brca2-deficient tumor growth in mice by Mlh1 loss. Furthermore, we described estrogen as inducing MLH1 expression through estrogen receptor α (ERα), which might explain why the majority of BRCA2 mutation carriers develop ER-positive breast cancer. Taken together, our findings reveal a role of MLH1 in relieving replicative stress and show how it may contribute to the establishment of BRCA2-deficient breast tumors.

Using diffusion of innovation framework with attitudinal factor to predict the future of mobility in the Indian market.

Rising temperatures across the world is posing a serious challenge to the longevity of earth's natural cycle. Use of private and conventional cars is growing year by year as standard of living continues to increase and affordability remaining no more of an issue for a significant proportion of the population. However, there has been a growing voice from segments of the society for a behavioural shift towards more sustainable modes of transport like usage of electric vehicles (EVs), mobility sharing and rental services and public transportation powered by electricity. One of the biggest importers of foreign crude oil, India, is reeling under immense pressure to reduce its carbon dioxide emissions and thereby contributing to environment protection. In India, the statistics or stock of EVs continues to remain poor when compared to its counterparts like China. Hence, this study is conducted to predict the influence of factors on purchase intention of consumers with respect to EVs in the Indian context. A questionnaire was prepared and circulated in New Delhi region to gather the responses people hold about this new technology based on the diffusion of innovation framework. The data of 225 respondents was analysed with the help of SPSS and AMOS software. Structural equation modelling technique was applied to test the hypotheses of this research. The results indicate that attitude has the most influential impact on purchase intention followed by related advantages but consumers also believe EVs to be complex in terms of their usability, limited availability and the absence of required public charging infrastructure. The mediating role of attitude between determinants of diffusion and purchase intention was also established except in the case of complexity. This study is contemporary and adds to the limited literature available on EV adoption in the Indian market by integrating attitudinal factor within the DOI framework. It also provides suitable insights to further the development of EVs in the domestic and global market.

Base-resolution UV footprinting by sequencing reveals distinctive damage signatures for DNA-binding proteins.

Decades ago, it was shown that proteins binding to DNA can quantitatively alter the formation of DNA damage by UV light. This established the principle of UV footprinting for non-intrusive study of protein-DNA contacts in living cells, albeit at limited scale and precision. Here, we perform deep base-resolution quantification of the principal UV damage lesion, the cyclobutane pyrimidine dimer (CPD), at select human promoter regions using targeted CPD sequencing. Several transcription factors exhibited distinctive and repeatable damage signatures indicative of site occupancy, involving strong (up to 17-fold) position-specific elevations and reductions in CPD formation frequency relative to naked DNA. Positive damage modulation at some ETS transcription factor binding sites coincided at base level with melanoma somatic mutation hotspots. Our work provides proof of concept for the study of protein-DNA interactions at individual loci using light and sequencing, and reveals widespread and potent modulation of UV damage in regulatory regions.

Presumptive ocular tuberculosis: A case series of rare cases.

Ocular tuberculosis (TB) may present with various clinical manifestations and may involve any part of the eye. In 80% of cases, pulmonary involvement is not found. Here, we are presenting three cases of presumptive ocular TB with three rare manifestations. The first case is of bilateral retinal detachment involving one eye after another, the second case is of tubercular phlyctenular keratoconjunctivitis with keratolysis, and the third case is of bilateral neuroretinitis with extensive cerebral involvement. Despite the availability of various tests, clinical findings, tuberculin skin test, chest X-ray, and computed tomography of the chest is still the primary basis of diagnosis of ocular TB in the tubercular endemic area, even in rare cases.

Mapping of QTLs for morphophysiological and yield traits under water-deficit stress and well-watered conditions in maize.

Maize productivity is significantly impacted by drought; therefore, improvement of drought tolerance is a critical goal in maize breeding. To achieve this, a better understanding of the genetic basis of drought tolerance is necessary. Our study aimed to identify genomic regions associated with drought tolerance-related traits by phenotyping a mapping population of recombinant inbred lines (RILs) for two seasons under well-watered (WW) and water-deficit (WD) conditions. We also used single nucleotide polymorphism (SNP) genotyping through genotyping-by-sequencing to map these regions and attempted to identify candidate genes responsible for the observed phenotypic variation. Phenotyping of the RILs population revealed significant variability in most of the traits, with normal frequency distributions, indicating their polygenic nature. We generated a linkage map using 1,241 polymorphic SNPs distributed over 10 chromosomes (chrs), covering a total genetic distance of 5,471.55 cM. We identified 27 quantitative trait loci (QTLs) associated with various morphophysiological and yield-related traits, with 13 QTLs identified under WW conditions and 12 under WD conditions. We found one common major QTL (qCW2-1) for cob weight and a minor QTL (qCH1-1) for cob height that were consistently identified under both water regimes. We also detected one major and one minor QTL for the Normalized Difference Vegetation Index (NDVI) trait under WD conditions on chr 2, bin 2.10. Furthermore, we identified one major QTL (qCH1-2) and one minor QTL (qCH1-1) on chr 1 that were located at different genomic positions to those identified in earlier studies. We found co-localized QTLs for stomatal conductance and grain yield on chr 6 (qgs6-2 and qGY6-1), while co-localized QTLs for stomatal conductance and transpiration rate were identified on chr 7 (qgs7-1 and qTR7-1). We also attempted to identify the candidate genes responsible for the observed phenotypic variation; our analysis revealed that the major candidate genes associated with QTLs detected under water deficit conditions were related to growth and development, senescence, abscisic acid (ABA) signaling, signal transduction, and transporter activity in stress tolerance. The QTL regions identified in this study may be useful in designing markers that can be utilized in marker-assisted selection breeding. In addition, the putative candidate genes can be isolated and functionally characterized so that their role in imparting drought tolerance can be more fully understood.