Synthesis, properties and antibacterial activity of Ca doped Zn2SnO4 nanoparticles by microwave assisted method.

A major problem in world health care is the development of antibiotic resistance in bacteria. In light of this, pure and calcium-doped zinc tin oxide (ZTO) nanoparticles, Zn2SnO4 (S1), Zn2Sn0.7Ca0.3O4 (S2), Zn2Sn0.5Ca0.5O4 (S3), and Zn2Sn0.3Ca0.7O4 (S4), were synthesized via simple and cost effective microwave assisted method. The doping effect on antibacterial activity was studied in detail. The XRD spectrum revealed that all the deposited samples exhibited a spinel cubic structure. A decrease in crystallite size, an increase in strain and dislocation density was observed with an increase in Ca concentration. FESEM images exhibited an irregular and non-homogeneous nature with crystalline morphology having a physical dimension of nm size. EDAX confirmed the purity of deposited samples. We used the agar well diffusion technique to study the antibacterial activity of Gram-positive and Gram-negative bacteria. The doping of the ZTO matrix with Ca ions increased its antibacterial performance by 99% against Klebsiella pneumoniae bacteria, and its effectiveness was enhanced with increasing Ca ion concentration inside the Zn2SnO4 nanoparticles.

Morpho-physiological and biochemical responses of cotton (Gossypium hirsutum L.) genotypes upon sucking insect-pest infestations.

The effects of sucking insect-pests on the morpho-physiological and biochemical changes in the leaves of four cotton genotypes-Bio 100 BG-II and GCH-3 (highly tolerant); KDCHH-9810 BG-II and HS-6 (highly susceptible)-were examined. Compared to tolerant genotypes, susceptible genotypes showed a decrease in relative water content, specific leaf weight, leaf area, photosynthetic rate, and total chlorophyll content, with an increase in electrolyte leakage. Hydrogen peroxide and total soluble sugar content were higher in susceptible plants. In contrast, resistant plants had higher levels of total soluble protein, total phenolic content, gossypol content, tannin content, peroxidase activity, and polyphenol oxidase. The findings demonstrated that the Bio 100 BG-II and GCH-3 genotypes effectively offset the impact of sucking insect-pests by modifying the factors mentioned above. The KDCHH-9810 BG-II and HS-6 genotypes could not completely negate the effects of sucking insect-pests. Customized metabolites and total soluble protein are more efficient in protecting cotton plants from damage brought on by infestations of sucking insects and pests. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01253-w.

Mapping of host-parasite-microbiome interactions reveals metabolic determinants of tropism and tolerance in Chagas disease.

Chagas disease (CD) is a parasitic disease caused by Trypanosoma cruzi protozoa, presenting with cardiomyopathy, megaesophagus, and/or megacolon. To determine the mechanisms of gastrointestinal (GI) CD tissue tropism, we systematically characterized the spatial localization of infection-induced metabolic and microbiome alterations, in a mouse model of CD. Notably, the impact of the transition between acute and persistent infection differed between tissue sites, with sustained large-scale effects of infection in the esophagus and large intestine, providing a potential mechanism for the tropism of CD within the GI tract. Infection affected acylcarnitine metabolism; carnitine supplementation prevented acute-stage CD mortality without affecting parasite burden by mitigating infection-induced metabolic disturbances and reducing cardiac strain. Overall, results identified a previously-unknown mechanism of disease tolerance in CD, with potential for new therapeutic regimen development. More broadly, results highlight the potential of spatially resolved metabolomics to provide insight into disease pathogenesis and infectious disease drug development.

Identification of potential CRAC channel inhibitors: Pharmacophore mapping, 3D-QSAR modelling, and molecular docking approach.

Upregulation of store-operated Ca2+ influx via ORAI1, an integral component of the CRAC channel, is responsible for abnormal cytokine release in active rheumatoid arthritis, and therefore ORAI1 has been proposed as an attractive molecular target. In this study, we attempted to predict the mechanical insights of ORAI1 inhibitors through pharmacophore modelling, 3D-QSAR, molecular docking and free energy analysis. Various hypotheses of pharmacophores were generated and from that, a pharmacophore hypothesis with two hydrogen bond acceptors, one hydrogen bond donor and two aromatic rings (AADRR) resulted in a statistically significant 3D-QSAR model (r2 = 0.84 and q2 = 0.74). We believe that the obtained statistical model is a reliable QSAR model for the diverse dataset of inhibitors against the IL-2 production assay. The visualization of contours in active and inactive compounds generated from the 3D-QSAR models and molecular docking studies revealed major interaction with GLN108, HIS113 and ASP114, and interestingly, these residues are located near the Ca2+ selectivity filter region. Free energy binding analysis revealed that Coulomb energy, van der Waals energy and non-polar solvation terms are more favourable for ligand binding. Thus, the present study provides the physical and chemical requirements for the development of novel ORAI1 inhibitors with improved biological activity.

Genome-based, mechanism-driven computational modeling of risks of ionizing radiation: The next frontier in genetic risk estimation?

Research activity in the field of estimation of genetic risks of ionizing radiation to human populations started in the late 1940s and now appears to be passing through a plateau phase. This paper provides a background to the concepts, findings and methods of risk estimation that guided the field through the period of its growth to the beginning of the 21st century. It draws attention to several key facts: (a) thus far, genetic risk estimates have been made indirectly using mutation data collected in mouse radiation studies; (b) important uncertainties and unsolved problems remain, one notable example being that we still do not know the sensitivity of human female germ cells to radiation-induced mutations; and (c) the concept that dominated the field thus far, namely, that radiation exposures to germ cells can result in single gene diseases in the descendants of those exposed has been replaced by the concept that radiation exposure can cause DNA deletions, often involving more than one gene. Genetic risk estimation now encompasses work devoted to studies on DNA deletions induced in human germ cells, their expected frequencies, and phenotypes and associated clinical consequences in the progeny. We argue that the time is ripe to embark on a human genome-based, mechanism-driven, computational modeling of genetic risks of ionizing radiation, and we present a provisional framework for catalyzing research in the field in the 21st century.

Reflections on the origins and evolution of genetic toxicology and the Environmental Mutagen Society.

This article traces the development of the field of mutagenesis and its metamorphosis into the research area we now call genetic toxicology. In 1969, this transitional event led to the founding of the Environmental Mutagen Society (EMS). The charter of this new Society was to "encourage interest in and study of mutagens in the human environment, particularly as these may be of concern to public health." As the mutagenesis field unfolded and expanded, new wording appeared to better describe this evolving area of research. The term "genetic toxicology" was coined and became an important subspecialty of the broad area of toxicology. Genetic toxicology is now set for a thorough reappraisal of its methods, goals, and priorities to meet the challenges of the 21st Century. To better understand these challenges, we have revisited the primary goal that the EMS founders had in mind for the Society's main mission and objective, namely, the quantitative assessment of genetic (hereditary) risks to human populations exposed to environmental agents. We also have reflected upon some of the seminal events over the last 40 years that have influenced the advancement of the genetic toxicology discipline and the extent to which the Society's major goal and allied objectives have been achieved. Additionally, we have provided suggestions on how EMS can further advance the science of genetic toxicology in the postgenome era. Any oversight or failure to make proper acknowledgment of individuals, events, or the citation of relevant references in this article is unintentional.

Behavioural risk factors for non communicable diseases among adults in Kerala, India.

BACKGROUND & OBJECTIVE: Cardiovascular and other chronic diseases are becoming the major causes of morbidity and mortality in most of the third world countries including India, especially in the southern Indian States, like Kerala, where most of the health indicators match closely with those of any developed country. Various behavioural risk factors (BRF) namely smoking, unhealthy diet, stress at home and work place, consumption of alcohol, sedentary life style, etc., are known to be risk factors for many such diseases. The present study was carried out to estimate the prevalence of various behavioural risk factors for chronic diseases, and to identify their biosocial correlates. METHODS: A cross-sectional study was done in which the data were collected from a sample of 6579 individuals of age 30 to 74 yr, randomly selected following a stratified multi-stage cluster sampling design covering Kerala State. The important factors investigated include various behavioural risk factors, presenting chronic diseases and family histories among close relatives. The data were analysed using both univariate and multivariate analyses. RESULTS: The two major risk factors observed among males were smoking and alcohol consumption. About two fifths (40%) of them were current smokers as well as current users of alcohol (41%). The median age at initiation was 21 yr for both smoking habits and for alcohol consumption. Nearly a quarter of the target population were inactive (23% males and 22% females) based on work and leisure time activities. More than one-fifth of them (23%) reported stress. Obesity was found more among females (33%) than males (17%). Low socio-economic background was found to be a high predictor (high risk group) for habit of smoking, alcohol consumption, stress and unhealthy diet. INTERPRETATION & CONCLUSION: Substantially high levels of the various behavioural risk factors among adults in Kerala suggests an urgent need for adopting healthy life style modifications among the population in general. The increased risk observed among the younger generation for behavioural risk factors such as smoking and alcohol consumption calls for urgent corrective steps and measures for long-term monitoring of all major risk factors as well as the major chronic disease conditions.

Reflections on the impact of advances in the assessment of genetic risks of exposure to ionizing radiation on international radiation protection recommendations between the mid-1950s and the present.

Efforts at protecting people against the harmful effects of radiation had their beginnings in the early 1900s with the intent of protecting individuals in medicine and associated professions. Such efforts remain vital for all of us more than 100 years later as part of our 'learning to live with ionizing radiation.' The field of radiation protection has evolved slowly over time with advances in knowledge on hereditary (i.e., genetic) and carcinogenic effects of radiation continually improving our ability to make informed judgments about how best to balance risks against benefits of radiation exposure. This paper examines just one aspect of these efforts, namely, how advances in knowledge of genetic effects of radiation have impacted on the recommendations of the International Commission on Radiological Protection (ICRP). The focus is on the period from the mid-1950s (when genetic risk estimates were first made) to 2007. This article offers a detailed historical analysis and personal perspective, and concludes with a synopsis of key developments in radiation protection.

New approaches to assessing the effects of mutagenic agents on the integrity of the human genome.

Heritable genetic alterations, although individually rare, have a substantial collective health impact. Approximately 20% of these are new mutations of unknown cause. Assessment of the effect of exposures to DNA damaging agents, i.e. mutagenic chemicals and radiations, on the integrity of the human genome and on the occurrence of genetic disease remains a daunting challenge. Recent insights may explain why previous examination of human exposures to ionizing radiation, as in Hiroshima and Nagasaki, failed to reveal heritable genetic effects. New opportunities to assess the heritable genetic damaging effects of environmental mutagens are afforded by: (1) integration of knowledge on the molecular nature of genetic disorders and the molecular effects of mutagens; (2) the development of more practical assays for germline mutagenesis; (3) the likely use of population-based genetic screening in personalized medicine.

Estimation of the genetic risks of exposure to ionizing radiation in humans: current status and emerging perspectives.

The 2001 report of the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) on ;Hereditary effects of radiation' incorporates two important concepts that have emerged from advances in radiation genetics and molecular biology: (a) most radiation-induced mutations are DNA deletions, often encompassing multiple genes; however, because of structural and functional constraints, only a proportion of induced deletions may be compatible with viability and hence recoverable in the progeny and (b) viability-compatible DNA deletions induced in human germ cells are more likely to cause multi-system developmental abnormalities rather than single-gene diseases. The work reported in this paper pursues these concepts further: it examines how mechanistic insights gained from studies of repair of radiation-induced DNA double-strand breaks (DSBs) in mammalian somatic cells and from those on the origin of deletions in human genomic disorders can be extended to germ cells the aim being the development of a framework to predict regions of the human genome that may be susceptible to radiation-induced deletions. A critical analysis of the available information permits the hypothesis that in stem cell spermatogonia, most induced deletions may arise via the non-homologous end joining (NHEJ) mechanism of DSB repair whereas in irradiated oocytes, the main mechanism is likely to be non-allelic homologous recombination (NAHR) between misaligned region-specific segmental duplications that are present in the genome (NAHR is an error-prone form of homologous recombination repair). Should this hypothesis turn out to be valid, then it is possible to build on the structural and functional aspects of genomic knowledge to devise strategies to predict where in the genome deletions may be induced by radiation, their extent and their potential phenotypes.

Oil massage in neonates: an open randomized controlled study of coconut versus mineral oil.

INTRODUCTION: Oil massage for newborns is reported to improve weight gain by better thermoregulation. A role for transcutaneous absorption has also been suggested. AIMS AND OBJECTIVES: This study was undertaken to compare the effect of massage with coconut oil versus mineral oil and placebo (powder) on growth velocity and neuro-behavior in well term and preterm babies. STUDY DESIGN: Open Randomized Controlled trial. SETTING: The Premature unit and the postnatal wards of a major teaching hospital in a metropolitan city. MATERIAL AND METHODS: Intramural preterm appropriate for gestational age babies weighing between 1500 to 2000 grams and term births weighing more than 2500 grams fulfilling the inclusion criteria constituted the two gestation age categories studied. Babies in each group were randomized to receive massage with either coconut oil, mineral oil or with placebo. Oil massage was given by a trained person from day 2 of life till discharge, and thereafter by the mother until 31 days of age, four times a day. Babies were followed up daily till discharge and every week after discharge for anthropometry. Neuro-behavioral outcome was assessed by the Brazelton Score at baseline, day 7 and on day 31. RESULTS: Coconut oil massage resulted in significantly greater weight gain velocity as compared to mineral oil and placebo in the preterm babies group; and in the term baby group, as compared to the placebo. Preterm infants receiving coconut oil massage also showed a greater length gain velocity compared to placebo group. No statistically significant difference was observed in the neurobehavioral assessment between all three subgroups in term babies as well as in preterm babies.

Ionizing radiation and genetic risks XIV. Potential research directions in the post-genome era based on knowledge of repair of radiation-induced DNA double-strand breaks in mammalian somatic cells and the origin of deletions associated with human genomic disorders.

Recent estimates of genetic risks from exposure of human populations to ionizing radiation are those presented in the 2001 report of the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). These estimates incorporate two important concepts, namely, the following: (1) most radiation-induced mutations are DNA deletions, often encompassing multiple genes, but only a small proportion of the induced deletions is compatible with offspring viability; and (2) the viability-compatible deletions induced in germ cells are more likely to manifest themselves as multi-system developmental anomalies rather than as single gene disorders. This paper: (a) pursues these concepts further in the light of knowledge of mechanisms of origin of deletions and other rearrangements from two fields of contemporary research: repair of radiation-induced DNA double-strand breaks (DSBs) in mammalian somatic cells and human molecular genetics; and (b) extends them to deletions induced in the germ cell stages of importance for radiation risk estimation, namely, stem cell spermatogonia in males and oocytes in females. DSB repair studies in somatic cells have elucidated the roles of two mechanistically distinct pathways, namely, homologous recombination repair (HRR) that utilizes extensive sequence homology and non-homologous end-joining (NHEJ) that requires little or no homology at the junctions. A third process, single-strand annealing (SSA), which utilizes short direct repeat sequences, is considered a variant of HRR. HRR is most efficient in late S and G2 phases of the cell cycle and is a high fidelity mechanism. NHEJ operates in all cell cycle phases, but is especially important in G1. In the context of radiation-induced DSBs, NHEJ is error-prone. SSA is also an error-prone mechanism and its role is presumably similar to that of HRR. Studies in human molecular genetics have demonstrated that the occurrence of large deletions, duplications or other rearrangements in certain regions of the genome is related to the presence of large segments of repetitive DNA called segmental duplications (also called duplicons or low copy repeats, LCRs) in such regions. The mechanism that is envisaged for the origin of deletions and other rearrangements involves misalignment of region-specific LCRs of homologous chromosomes in meiosis followed by unequal crossing-over (i.e., non-allelic homologous recombination, NAHR). We hypothesize that: (a) in spermatogonial stem cells, NHEJ is probably the principal mechanism underlying the origin of radiation-induced deletions, although SSA and NAHR may also be involved to some extent, especially at low doses; and (b) in irradiated oocytes, NAHR is likely to be the main mechanism for generating deletions. We suggest future research possibilities, including the development of models for identifying regions of the genome that are susceptible to radiation-induced deletions. Such efforts may have particular significance in the context of the estimation of genetic risks of radiation exposure of human females, a problem that is still with us.

Congenital rickets.

Although rickets in premature newborns is known to occur, term babies presenting at birth is uncommon. We report a term baby born to a mother with osteomalacia, and presented at birth with signs of florid rickets which was confirmed biochemically. After 4 weeks of treatment, radiological signs of healing were seen.

Impact of cancer predisposition and radiosensitivity on the population risk of radiation-induced cancers.

This paper provides a brief overview of the current evidence for cancer predisposition and for an increased sensitivity of individuals carrying such predisposing mutations to cancers induced by ionizing radiations. We also discuss the use of a Mendelian one-locus, two-allele autosomal dominant model for predicting the impact of cancer predisposition and increased radiosensitivity on the risk of radiation-induced cancers in the population and in relatives of affected individuals using breast cancer due to BRCA1 mutations as an example. The main conclusions are the following: (1) The relative risk ratio of the risks of radiation-induced cancer in a heterogeneous population which has subgroups of normal and cancer-predisposed individuals to the risks in a homogeneous population (i.e., one which does not have these subgroups) increases with increasing dose; however, the dose dependence of the RR decreases at higher doses because of the fact that at high doses, the radiation risk to a homogeneous population will already be high. (2) The attributable risk (the proportion of cancers attributable to increased cancer susceptibility and increased radiosensitivity) follows a similar pattern. (3) When the proportion of cancers due to the susceptible genotypes is small (< 10%), as is likely to be the case for breast cancers in non-Ashkenazi Jewish women, the increases in risk ratios and attributable risks are small, and become marked only when there are very large increases in cancer susceptibility (> 1000-fold) and radiosensitivity (> 100-fold) in the susceptible group. (4) When the proportion of cancers due to the susceptible genotypes is appreciable (> or = 10%), as may be the case for breast cancers in Ashkenazi Jewish women, there may be significant increases in the risk ratios and attributable risk for comparatively moderate increases in cancer susceptibility (> 10-fold) and radiosensitivity (> 100-fold) in the susceptible subpopulation. (5) The ratio of the risk of radiation-induced cancer in relatives to that in unrelated individuals in the population increases with the biological relatedness of the relative, being higher for close than for distant relatives; however, even when the mutant BRCA1 gene frequency and the proportion of breast cancers due to these mutations are high, as in Ashkenazi Jewish women, for values of predisposition strength and radiosensitivity differential < 10, the increase in breast cancer risks is only marginal, even for first-degree relatives.

Estimation of the hereditary risks of exposure to ionizing radiation: history, current status, and emerging perspectives.

This paper provides a brief overview of the advances in the field of the estimation of the genetic risks of exposure of human populations to ionizing radiation from the early 1950's to the present and of the developments that are anticipated in the coming years. The latter are based on the view that the insights gained from human genetics, especially human molecular genetics, will be increasingly applied to address problems in risk estimation. Owing to the paucity of human data on radiation-induced mutations, mouse data on radiation-induced mutations are used to predict the risk of genetic diseases in humans using the doubling dose method. With this method, the risk per unit dose is expressed as a product of three quantities, i.e., P x 1/DD x MC where P is the baseline frequency of genetic diseases, 1/DD (the relative mutation risk per unit dose; DD refers to the doubling dose, i.e., the radiation dose required to produce as many mutations as those that occur spontaneously in a generation) and MC is the disease class-specific mutation component (a measure of the relative increase in disease frequency per unit relative increase in mutation rate). The five important changes that are now introduced in genetic risk estimation include (1) an upward revision of the baseline frequency of Mendelian diseases to 2.4% (from 1.25% used until the early 1990's); (2) a reversion to the conceptual basis for DD calculations used in the 1972 BEIR report of the U.S. National Academy of Sciences, namely, the use of human data on spontaneous mutation rates and mouse data on induced mutation rates (instead of the use of mouse data for both these rates as has been the case from mid-1970's until the early 1990's); (3) the fuller development and use of the MC concept for predicting the responsiveness of Mendelian and multifactorial diseases to increases in mutation rate; (4) the introduction of a new disease-class-specific quantity called the "potential recoverability correction factor" or PRCF in the risk equation to bridge the gap between the rates of induced mutations in mice and the risk of inducible genetic diseases in humans; and (5) the introduction of the concept that multisystem developmental abnormalities are likely to be among the principal phenotypes of radiation induced genetic damage in humans. All these advances now permit, for the first time in 40 y, the estimation of risks for all classes of genetic diseases. For a population exposed to low-LET, chronic or low-dose irradiation, the risks predicted for the first generation progeny are the following (all estimates are per million live born progeny per gray of parental irradiation): autosomal dominant and x-linked diseases, approximately 750 to 1,500 cases; autosomal recessive, nearly zero; chronic multifactorial diseases, approximately 250 to 1,200 cases; and congenital abnormalities, approximately 2000 cases. The total risk per gray is of the order of approximately 3,000 to 4,700 cases, which represent approximately 0.4 to 0.6% of the baseline frequency of these diseases (738,000 per million) in the population. The advances anticipated in the coming years are likely to permit the estimation of genetic risks of radiation with greater precision than is now possible.

Estimation of genetic risks of exposure to ionizing radiation: status in the year 2000.

This paper provides an overview of the advances in the estimation of genetic risks of exposure of human populations to ionizing radiation with particular emphasis on the advances during the last decade. Among the latter are: (a) an upward revision of the estimates of the baseline frequencies of Mendelian diseases (from 1.25 to 2.4%); (b) the conceptual change to the use of a doubling dose based on human data on spontaneous mutation rates and mouse data on induced mutation rates (from the one based entirely on mouse data on spontaneous and induced mutation rates, which was the case thus far); (c) the fuller development of the concept of mutation component (MC) and its application to predict the responsiveness of Mendelian and chronic multifactorial diseases to induced mutations; (d) the concept that the major adverse effects of radiation exposure of human germ cells are likely to be manifest as multi-system developmental abnormalities and (e) the concept of potential recoverability correction factor (PRCF) to bridge the gap between induced mutations studied in mice and the risk of genetic disease in humans. For a population exposed to low LET, chronic/low dose-rate irradiation, the current estimates of risk for the first generation progeny are the following (all estimates per million live born progeny per Gy of parental irradiation): autosomal dominant and X-linked diseases, approximately 750 to 1,500 cases; autosomal recessive, nearly zero; chronic multifactorial diseases, approximately 250 to 1,200 cases and congenital abnormalities, approximately 2,000 cases. The total risk per Gy is of the order of approximately 3,000 to 4,700 cases which represent approximately 0.4 to 0.6% of the baseline frequency of these diseases. The main message is that at low doses of radiation of interest in risk estimation, the risk of adverse hereditary effects is small.