Trend and disparities in authorship of healthcare-related publications on the ongoing Russia-Ukraine war.

BACKGROUND: The Russia-Ukraine war has undeniably impacted global science and healthcare in Ukraine. Many Ukrainian researchers have had their projects disrupted by this war, either due to loss of life, displacement, or destruction of resources. Despite these challenges, these researchers have sought to make their voices heard. This scoping review highlights the trend of healthcare-related publications on the current Russia-Ukraine war and characterizes the contribution of Ukrainian authors to these publications. METHOD: A comprehensive literature search was performed using two databases (Scopus and Pubmed) for publications related to the ongoing Russia-Ukraine war. We included articles only related to healthcare. We then extracted and analyzed bibliometric data. RESULT: One hundred and eighty-three articles were identified, including 12 (6.6%) original articles, 26 (14.2%) cross-sectional studies, 19 (10.4%) letters to the editor, 10 (5.5%) commentaries, 5 (2.7%) perspectives, 35 (19.1%) editorials, 2 (1.1%) randomized controlled trials, 11(6.0%) correspondences, 13 (7.1%) opinions, 8 (4.4%) reviews and 42 (23.0%) are identified as others. 180 (98.4%) studies were in English, and 3 (1.7%) were in German. 54 (29.5%) papers on the war had at least one author affiliated with a Ukrainian institution, and 29 (15.9%) studies had authors with Ukrainian affiliation as first authors. CONCLUSION: our study shows that there has been a significant number of publications on the Russia-Ukraine war and only a small portion of first authors, co-authors, and last authors of these publications are affiliated to an institution in Ukraine. Therefore, despite the relatively high number of publications, most publications do not arise from the perspective of Ukrainian authors.

Thiosulfate impregnated spent tea leaves for the remarkable uptake of malachite green.

Herein we demonstrate an enhanced performance of acid-assisted thiosulfate-impregnated spent/waste tea leaves (TWTL) for the removal of malachite green (MG) from water by batch mode. The material was characterized by pHZPC, FTIR, powder XRD, SEM, and proximate analysis. FTIR suggests the presence of polyphenolic moieties whereas a lignocellulosic peak was observed in powder XRD. SEM image shows a grafted surface texture with intermittent blocks, which upon dye uptake becomes somewhat condensed. Under optimized conditions, the highest removal efficiency of 126.8 mg/g was achieved at pH 7. A fast adsorption process was noticed with >97% removal within the first 10 min. Adsorption follows pseudo-second-order kinetics (R2 = 0.999) and the Langmuir model (R2 = 0.999). The material can be regenerated by dilute hydrochloric acid and can be reused for up to four cycles. Treatment of industrial effluent was successful in up to 47.56%. Our results highlight the potential of thiosulfate-treated spent tea leaves as a choice for the efficient removal of malachite green from water.

Tea, being one of the most popular beverages produces huge waste which requires proper management. With this aim; the thiosulfate-impregnated spent tea leaves have been exercised for effective separation of malachite green from contaminated water. Thiosulfate impregnation under mildly acidic conditions activates the tea leaves and makes the material robust with enhanced water stability than its untreated variety. With a remarkable maximum adsorption capacity of 126.8 mg/g under ambient conditions, the present methodology enjoys the edge over related phytosorbents. The protocol is techno-economic, environment friendly, and could be extended to possible field applications.

Reassessing the availability of crop residue as a bioenergy resource in India: A field-survey based study.

Second-generation bioenergy, a carbon neutral or negative renewable resource, is crucial to achieving India's net-zero emission targets. Crop residues are being targeted as a bioenergy resource as they are otherwise burned on-field, leading to significant pollutant emissions. But estimating their bioenergy potential is problematic because of broad assumptions about their surplus fractions. Here, we use comprehensive surveys and multivariate regression models to estimate the bioenergy potential of surplus crop residues in India. These are with high sub-national and crop disaggregation that can facilitate the development of efficient supply chain mechanisms for its widespread usage. The estimated potential for 2019 of 1313 PJ can increase the present bioenergy installed capacity by 82% but is likely insufficient alone to meet India's bioenergy targets. The shortage of crop residue for bioenergy, combined with the sustainability concerns raised by previous studies, imply a need to reassess the strategy for the use of this resource.

Prevalence of pulmonary hypertension in chronic simple silicosis patients and its correlation with smoking history, occupation type, age and duration of silica exposure.

Silicosis is a preventable occupational health hazard with potential for permanent physical disability and increased socio-economic burden. Pulmonary hypertension (PH) secondary to chronic respiratory diseases signifies poorer prognosis and transthoracic echocardiography (TTE) has proven its usefulness as a screening tool for PH diagnosis. The objectives were to determine PH prevalence in chronic simple silicosis patients through TTE screening and correlate PH prevalence with smoking status, occupation type, age and duration of silica exposure (DSE). We enrolled 104 patients in the study based on occupational exposure to silica dust and radiologic confirmation of chronic simple silicosis. The study sample was divided into significant smokers (SS group) and insignificant smokers (InS group) on the basis of ≥10 pack years smoking history, and into drillers and dressers based on occupation type. TTE examination was performed to measure resting mean pulmonary artery pressure (mPAP) and the patients were classified into: no PH (mPAP≤20 mm Hg), borderline PH (mPAP>20 and <25 mmHg), and PH (mPAP≥25). PH prevalence was 25% in study subjects (26/104); 29.6% (16/54) among SS group versus 20% (10/50) among InS group (.52) ; and 34.2% (14/41) among drillers versus 19.1% (12/63) among dressers (p=.024). Mean age and mean duration of silica exposure among SS and InS groups were comparatively similar, while they had lower values among dressers against dressers with no statistical significance. Logistic regression analysis established a significant association of PH prevalence with higher age in the study sample, SS group and drillers group, while a significant association of PH prevalence with longer DSE was only seen in the study sample. PH prevalence was significantly associated (p=.007) with SS-driller group on comparing TTE findings with combined smoking and occupation type based groups. This study has shown PH prevalence in chronic simple silicosis patients at alarming levels, having associations with driller occupation, older age and longer DSE with varying results among groups and complex interplay with smoking exposure, suggesting the need for large sample-based molecular and genetic studies. Including TTE in the initial work-up of silicosis patients will promote timely intervention and reduce morbidity and mortality with a high benefit-cost ratio.

Targeting Artemisinin-Resistant Malaria by Repurposing the Anti-Hepatitis C Virus Drug Alisporivir.

The emergence of Plasmodium falciparum resistance raises an urgent need to find new antimalarial drugs. Here, we report the rational repurposing of the anti-hepatitis C virus drug, alisporivir, a nonimmunosuppressive analog of cyclosporin A, against artemisinin-resistant strains of P. falciparum. In silico docking studies and molecular dynamic simulation predicted strong interaction of alisporivir with PfCyclophilin 19B, confirmed through biophysical assays with a Kd value of 354.3 nM. Alisporivir showed potent antimalarial activity against chloroquine-resistant (PfRKL-9 with resistance index [Ri] 2.14 ± 0.23) and artemisinin-resistant (PfKelch13R539T with Ri 1.15 ± 0.04) parasites. The Ri is defined as the ratio between the IC50 values of the resistant line to that of the sensitive line. To further investigate the mechanism involved, we analyzed the expression level of PfCyclophilin 19B in artemisinin-resistant P. falciparum (PfKelch13R539T). Semiquantitative real-time transcript, Western blot, and immunofluorescence analyses confirmed the overexpression of PfCyclophilin 19B in PfKelch13R539T. A 50% inhibitory concentration in the nanomolar range, together with the targeting of PfCyclophilin 19B, suggests that alisporivir can be used in combination with artemisinin. Since artemisinin resistance slows the clearance of ring-stage parasites, we performed a ring survival assay on artemisinin-resistant strain PfKelch13R539T and found significant decrease in parasite survival with alisporivir. Alisporivir was found to act synergistically with dihydroartemisinin and increase its efficacy. Furthermore, alisporivir exhibited antimalarial activity in vivo. Altogether, with the rational target-based Repurposing of alisporivir against malaria, our results support the hypothesis that targeting resistance mechanisms is a viable approach toward dealing with drug-resistant parasite.

Validation of Novel spot blotch disease resistance alleles identified in unexplored wheat (Triticum aestivum L.) germplasm lines through KASP markers.

BACKGROUND: During the last few decades, the diverse sources of resistance, several genes and QTLs for spot blotch resistance have been identified. However, a large set of germplasm lines are still unexplored that have the potential to develop highly resistant wheat cultivars for the target environments. Therefore, the identification of new sources of resistance to spot blotch is essential for breeding programmes to develop spot blotch resistant cultivars and sustain wheat production. The association mapping panel of 294 diverse bread wheat accessions was used to explore new sources of spot blotch disease resistance and to identify genomic regions using genome wide association analysis (GWAS). The genotypes were tested in replicated trials for spot blotch disease at three major hot spots in India (Varanasi in UP, Pusa in Bihar, and Cooch Behar in West Bengal). The area under the disease progress curve (AUDPC) was calculated to assess the level of resistance in each genotype. RESULTS: A total of 19 highly and 76 moderately resistant lines were identified. Three accessions (EC664204, IC534306 and IC535188) were nearly immune to spot blotch disease. The genotyping of all accessions resulted in a total of 16,787 high-quality polymorphic SNPs. The GWAS was performed using a Compressed Mixed Linear Model (CMLM) and a Mixed Linear Model (MLM). A total of seven significant MTAs, common in both the models and consistent across the environment, were further validated to develop KASP markers. Four MTAs (AX-94710084, AX-94865722, AX-95135556, and AX-94529408) on three chromosomes (2AL, 2BL, and 3BL) have been successfully validated through the KASP marker. CONCLUSIONS: The new source of resistance was identified from unexplored germplasm lines. The genomic regions identified through GWAS were validated through KASP markers. The marker information and the highly resistant sources are valuable resources to rapidly develop immune or near immune wheat varieties.

The red seaweed Kappaphycus alvarezii antiporter gene (KaNa+/H+) confers abiotic stress tolerance in transgenic tobacco.

BACKGROUND: Plant establishment, growth, development and productivity are adversely affected by abiotic stresses that are dominant characteristics of environmentally challenged/degraded habitats created in the Anthropocene. Crop breeding for climate resilience properties is need of the hour to sustain the crop productivity. We report on the characterization of Kappaphycus alvarezii (a red seaweed) Na+/H+ antiporter gene (KaNa+/H+) for enhanced salt and osmotic stress tolerance. METHODS: The KaNa+/H+ antiporter gene was cloned and over-expressed in tobacco under the control of CaMV35S promoter. Transgenic analysis was carried out to assess the stress tolerance ability of tobacco over-expressing KaNa+/H+ antiporter gene. RESULTS: Over-expression of KaNa+/H+ gene improved the seed germination and seed vigor index under stress. Transgenic plants grew better and exhibited delayed leaf senescence. Improved K+/Na+, carotenoid/total chlorophyll and relative water content; lower accumulation of reactive oxygen species (ROS), MDA and Na+; lower electrolyte leakage; better membrane stability index and accumulation of K+, photosynthetic pigment, starch, sugar, free amino acid, proline and polyphenol contents indicated better physiological health of the transgenic tobacco under stress. Transgenic tobacco exhibited higher photosynthesis, photosystem II efficiency, electron transfer rate, photochemical quenching and activity of water splitting complex. Compared with control tobacco, transgenic tobacco exhibited higher expression of stress-defence genes under stress and better recovery after long-term osmotic stress. CONCLUSIONS: Lower Na+ cytotoxicity, lower accumulation of ROS and maintenance of the membrane integrity helped transgenic tobacco to maintain the physiological functioning under stress. Present results established K. alvarezii as a potential gene resource and the KaNa+/H+ antiporter gene as a potential candidate gene in molecular breeding of crops for development of the degraded land.

Genome-wide association mapping reveals key genomic regions for physiological and yield-related traits under salinity stress in wheat (Triticum aestivum L.).

A genome-wide association study (GWAS) was conducted using six different multi-locus GWAS models and 35K SNP array to demarcate genomic regions underlying reproductive stage salinity tolerance. Marker-trait association analysis was performed for salt tolerance indices (STI) of 11 morpho-physiological traits, and the actual concentrations of Na+ and K+, and the Na+/K+ ratio in flag leaf. A total of 293 significantly associated quantitative trait nucleotides (QTNs) for 14 morpho-physiological traits were identified. Of these 293 QTNs, 12 major QTNs with R2 ≥ 10.0% were detected in three or more GWAS models. Novel major QTNs were identified for plant height, number of effective tillers, biomass, grain yield, thousand grain weight, Na+ and K+ content, and the Na+/K+ ratio in flag leaf. Moreover, 48 candidate genes were identified from the associated genomic regions. The QTNs identified in this study could potentially be targeted for improving salinity tolerance in wheat.

Magnetic Stiffening in 3D Cell Culture Matrices.

The mechanical environment of a cell is not constant. This dynamic behavior is exceedingly difficult to capture in (synthetic) in vitro matrices. This paper describes a novel, highly adaptive hybrid hydrogel composed of magnetically sensitive magnetite nanorods and a stress-responsive synthetic matrix. Nanorod rearrangement after application of (small) magnetic fields induces strain in the network, which results in a strong (over 10-fold) stiffening even at minimal (2.5 wt %) nanorod concentrations. Moreover, the stiffening mechanism yields a fast and fully reversible response. In the manuscript, we quantitatively analyze that forces generated by the particles are comparable to cellular forces. We demonstrate the value of magnetic stiffening in a 3D MCF10A epithelial cell experiment, where simply culturing on top of a permanent magnet gives rise to changes in the cell morphology. This work shows that our hydrogels are uniquely suited as 3D cell culture systems with on-demand adaptive mechanical properties.

Identification and evolutionary analysis of polycistronic miRNA clusters in domesticated and wild wheat.

MicroRNAs are ~22 nucleotide long non-coding RNAs that regulate gene expression at posttranscriptional level. Genome-wide analysis was performed to identify polycistronic miRNAs from wheat. Total 89 polycistronic miRNAs were identified in bread wheat which were distributed on three component sub-genomes (A = 26, B = 33 and D = 30). Except some, most of the identified polycistronic miRNAs were also present in other cultivated and wild wheat species. Expression of 11 identified polycistronic miRNAs could be validated using previously assembled transcriptomes, RNA-seq/s-RNA seq data of cultivated and wild wheats and RT-PCR. Polycistronic miRNAs orthologs were also localized on rice and Brachypodium genomes. As a case study, we also analyzed molecular evolution of miR395 family polycistrons in wheat. Both tandem and segmental duplications contributed to expansion of miR395 family polycistrons. Our findings provide a comprehensive view on wheat polycitronic miRNAs that will enable their in-depth functional analysis in the future.

Genetic Dissection of Seedling Root System Architectural Traits in a Diverse Panel of Hexaploid Wheat through Multi-Locus Genome-Wide Association Mapping for Improving Drought Tolerance.

Cultivars with efficient root systems play a major role in enhancing resource use efficiency, particularly water absorption, and thus in drought tolerance. In this study, a diverse wheat association panel of 136 wheat accessions including mini core subset was genotyped using Axiom 35k Breeders' Array to identify genomic regions associated with seedling stage root architecture and shoot traits using multi-locus genome-wide association studies (ML-GWAS). The association panel revealed a wide variation of 1.5- to 50-fold and were grouped into six clusters based on 15 traits. Six different ML-GWAS models revealed 456 significant quantitative trait nucleotides (QTNs) for various traits with phenotypic variance in the range of 0.12-38.60%. Of these, 87 QTNs were repeatedly detected by two or more models and were considered reliable genomic regions for the respective traits. Among these QTNs, eleven were associated with average diameter and nine each for second order lateral root number (SOLRN), root volume (RV) and root length density (RLD). A total of eleven genomic regions were pleiotropic and each controlled two or three traits. Some important candidate genes such as Formin homology 1, Ubiquitin-like domain superfamily and ATP-dependent 6-phosphofructokinase were identified from the associated genomic regions. The genomic regions/genes identified in this study could potentially be targeted for improving root traits and drought tolerance in wheat.

Fibroblast Activation Protein Targeted Photodynamic Therapy Selectively Kills Activated Skin Fibroblasts from Systemic Sclerosis Patients and Prevents Tissue Contraction.

Systemic sclerosis (SSc) is a rare, severe, auto-immune disease characterized by inflammation, vasculopathy and fibrosis. Activated (myo)fibroblasts are crucial drivers of this fibrosis. By exploiting their expression of fibroblast activation protein (FAP) to perform targeted photodynamic therapy (tPDT), we can locoregionally deplete these pathogenic cells. In this study, we explored the use of FAP-tPDT in primary skin fibroblasts from SSc patients, both in 2D and 3D cultures. Method: The FAP targeting antibody 28H1 was conjugated with the photosensitizer IRDye700DX. Primary skin fibroblasts were obtained from lesional skin biopsies of SSc patients via spontaneous outgrowth and subsequently cultured on plastic or collagen type I. For 2D FAP-tPDT, cells were incubated in buffer with or without the antibody-photosensitizer construct, washed after 4 h and exposed to λ = 689 nm light. Cell viability was measured using CellTiter Glo®®. For 3D FAP-tPDT, cells were seeded in collagen plugs and underwent the same treatment procedure. Contraction of the plugs was followed over time to determine myofibroblast activity. Results: FAP-tPDT resulted in antibody-dose dependent cytotoxicity in primary skin fibroblasts upon light exposure. Cells not exposed to light or incubated with an irrelevant antibody-photosensitizer construct did not show this response. FAP-tPDT fully prevented contraction of collagen plugs seeded with primary SSc fibroblasts. Even incubation with a very low dose of antibody (0.4 nM) inhibited contraction in 2 out of 3 donors. Conclusions: Here we have shown, for the first time, the potential of FAP-tPDT for the treatment of fibrosis in SSc skin.

Na+/K+-ATPase a Primary Membrane Transporter: An Overview and Recent Advances with Special Reference to Algae.

The maintenance of ionic homeostasis in the cytoplasm is an essential and crucial physiological process for all living beings. At cellular level, Na+ concentrations are maintained by specialized Na+ transporting molecular machines, which operate in the cell or plasma membrane. In eukaryotes Na+ transporting P-type ATPase play an important role in Na+ homeostasis that is known as Na+/K+-ATPase in animal cells in which K+ acts as a counter ion for the exchange of sodium. Na+/K+-ATPase is not found in plants. In plants and fungi, proton gradients are maintained by plasma membrane H+-ATPase while in animal cells Na+ and K+ gradient is maintained by Na+/K+-ATPase. However, in case of algae, a few reports of Na+/K+-ATPase are available, that maintains optimum concentration gradients in the cytoplasm and is used by Na+/H+ antiporter to exchange of Na+ and H+ ions. The membrane potential derived as a result of ion gradients across the membrane is base for a variety of cellular processes. An active Na+ dependent cycle (P-type ATPase) is scarcely reported in algae as compared to marine bacteria/cyanobacteria and animals. The characterization of these transporter gene-encoding membrane transports in seaweed would contribute to the understanding of abiotic stress tolerance in these organisms. This review highlights the detailed account of algal along with animal type Na+-ATPase i.e. occurrence, properties, significance and their recent progress.

Development of novel carbazole derivatives with effective multifunctional action against Alzheimer's diseases: Design, synthesis, in silico, in vitro and in vivo investigation.

Carbazole based novel multifunctional agents has been rationally designed and synthesized as potential anti-Alzheimer agents. Multi-functional activity of these derivatives have been assessed by performing various in-vitro assays and these compounds appeared to be potent AChE inhibitors, Aß aggregation inhibitors, anti-oxidant and neuroprotective agents. Among the entire series, MT-1 and MT-6 were most potent multifunctional agents which displayed effective and selective AChE inhibition, Aß disaggregation, anti-oxidant and metal chelation action. Neuroprotective activity of MT-6 has been examined against H2O2 induced toxicity in SHSY-5Y cells and they have shown effective neuroprotection. Additionally, MT-6 did not display any significant toxicity in SHSY-5Y cells, indicating its non-toxic nature. Molecular docking and MD simulation studies have been also performed to explore molecular level interaction with AChE and Aß. Finally, MT-6 was evaluated against scopolamine induced dementia model of mice and this compound actively improved memory deficit and cognition impairment in scopolamine treated mice. Thus, novel carbazole derivative MT-6 has been explored as an effective and safe multifunctional agent against AD and this molecule may be used as a suitable lead for development of effective anti-Alzheimer agents in future.

Prevalence and Risk Factors of Allergic Bronchopulmonary Aspergillosis and Aspergillus Sensitization in Children with Poorly Controlled Asthma.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) may be a risk factor for poorly controlled asthma in children. The studies regarding prevalence and risk factors of ABPA in children with poorly controlled asthma are limited in number. OBJECTIVES: To determine prevalence and risk factors of ABPA and aspergillus sensitization (AS) in children with poorly controlled asthma. METHODS: In this prospective cross-sectional study from a tertiary care center in India, we enrolled asthmatic children 5-15 years of age with poorly controlled asthma. We did the following investigations: spirometry, skin prick test, serum total immunoglobulin E (IgE), aspergillus-specific IgE and immunoglobulin G, serum precipitin for Aspergillus, absolute eosinophil count, chest X-ray and high-resolution computed tomography of the chest. ABPA and AS were diagnosed as per the recently proposed criteria. RESULTS: We enrolled 106 children [boys 72 (67.9%); mean age of 10.2 ± 2.6 years] with poorly controlled asthma. The prevalence of ABPA and AS were 11.3% (95% CI, 5.2-17.5%) and 61.3% (95% CI, 52.0-70.7%), respectively. The presence of brownish sputum was significantly more in ABPA compared with non-ABPA patients (33.3 vs. 4.2%, p = 0.002). The age, gender, allergic rhinitis and gastroesophageal reflux were not significantly different in ABPA compared with non-ABPA patients. CONCLUSION: The prevalence of ABPA and AS was 11.3 and 61.3%, respectively in children with poorly controlled asthma. We could not find any risk factors for ABPA except that the presence of brownish sputum was more in children with ABPA. Spirometry parameters were not significantly different in ABPA compared with non-ABPA patients.

Mitochondrial functions of RECQL4 are required for the prevention of aerobic glycolysis-dependent cell invasion.

Germline mutations in RECQL4 helicase are associated with Rothmund-Thomson syndrome, which is characterized by a predisposition to cancer. RECQL4 localizes to the mitochondria, where it acts as an accessory factor during mitochondrial DNA replication. To understand the specific mitochondrial functions of RECQL4, we created isogenic cell lines, in which the mitochondrial localization of the helicase was either retained or abolished. The mitochondrial integrity was affected due to the absence of RECQL4 in mitochondria, leading to a decrease in F1F0-ATP synthase activity. In cells where RECQL4 does not localize to mitochondria, the membrane potential was decreased, whereas ROS levels increased due to the presence of high levels of catalytically inactive SOD2. Inactive SOD2 accumulated owing to diminished SIRT3 activity. Lack of the mitochondrial functions of RECQL4 led to aerobic glycolysis that, in turn, led to an increased invasive capability within these cells. Together, this study demonstrates for the first time that, owing to its mitochondrial functions, the accessory mitochondrial replication helicase RECQL4 prevents the invasive step in the neoplastic transformation process.

Identification, analysis and development of salt responsive candidate gene based SSR markers in wheat.

BACKGROUND: Salinity severely limits wheat production in many parts of the world. Development of salt tolerant varieties represents the most practical option for enhancing wheat production from these areas. Application of marker assisted selection may assist in fast tracking development of salt tolerant wheat varieties. However, SSR markers available in the public domain are not specifically targeted to functional regions of wheat genome, therefore large numbers of these need to be analysed for identification of markers associated with traits of interest. With the availability of a fully annotated wheat genome assembly, it is possible to develop SSR markers specifically targeted to genic regions. We performed extensive analysis to identify candidate gene based SSRs and assessed their utility in characterizing molecular diversity in a panel of wheat genotypes. RESULTS: Our analysis revealed, 161 SSR motifs in 94 salt tolerance candidate genes of wheat. These SSR motifs were nearly equally distributed on the three wheat sub-genomes; 29.8% in A, 35.7% in B and 34.4% in D sub-genome. The maximum number of SSR motifs was present in exons (31.1%) followed by promoters (29.8%), 5'UTRs (21.1%), introns (14.3%) and 3'UTRs (3.7%). Out of the 65 candidate gene based SSR markers selected for validation, 30 were found polymorphic based on initial screening and employed for characterizing genetic diversity in a panel of wheat genotypes including salt tolerant and susceptible lines. These markers generated an average of 2.83 alleles/locus. Phylogenetic analysis revealed four clusters. Salt susceptible genotypes were mainly represented in clusters I and III, whereas high and moderate salt tolerant genotypes were distributed in the remaining two clusters. Population structure analysis revealed two sub-populations, sub-population 1 contained the majority of salt tolerant whereas sub-population 2 contained majority of susceptible genotypes. Moreover, we observed reasonably higher transferability of SSR markers to related wheat species. CONCLUSION: We have developed salt responsive gene based SSRs in wheat for the first time. These were highly useful in unravelling functional diversity among wheat genotypes with varying responses to salt stress. The identified gene based SSR markers will be valuable genomic resources for genetic/association mapping of salinity tolerance in wheat.

Diversity in protein profiling, pasting, empirical and dynamic dough rheological properties of meal from different durum wheat accessions.

The particle size distribution, protein profile, pasting and dough rheological properties of meal from forty-two Indian durum wheat accessions were evaluated. Meal from accessions with higher grain hardness index (GHI) showed a high proportion of large size particles with higher protein content and lower paste viscosities. Elastic and viscous modulii (G' and G″) of dough were negatively correlated with paste viscosities, which was associated with the presence/absence of LMW-GS and HMW-GS. Wheat accessions with allelic combinations of (13 + 16) with 97 + 91 kDa polypeptides (PPs) had higher G' and G″. The accession with 35 kDa PP showed higher while those with 35 and 62 kDa PPs showed lower paste viscosity. Among all accessions, 25 accessions possess 7 + 8 (97 and 88 kDa) type HMW-GS allelic combination. Durum accessions with diverse GHI, particle size distribution, protein profile, paste and dough rheology indicates their variation in milling and processing behaviour.

RECQL4 and p53 potentiate the activity of polymerase γ and maintain the integrity of the human mitochondrial genome.

UNLABELLED: Germline mutations in RECQL4 and p53 lead to cancer predisposition syndromes, Rothmund-Thomson syndrome (RTS) and Li-Fraumeni syndrome (LFS), respectively. RECQL4 is essential for the transport of p53 to the mitochondria under unstressed conditions. Here, we show that both RECQL4 and p53 interact with mitochondrial polymerase (PolγA/B2) and regulate its binding to the mitochondrial DNA (mtDNA) control region (D-loop). Both RECQL4 and p53 bind to the exonuclease and polymerase domains of PolγA. Kinetic constants for interactions between PolγA-RECQL4, PolγA-p53 and PolγB-p53 indicate that RECQL4 and p53 are accessory factors for PolγA-PolγB and PolγA-DNA interactions. RECQL4 enhances the binding of PolγA to DNA, thereby potentiating the exonuclease and polymerization activities of PolγA/B2. To investigate whether lack of RECQL4 and p53 results in increased mitochondrial genome instability, resequencing of the entire mitochondrial genome was undertaken from multiple RTS and LFS patient fibroblasts. We found multiple somatic mutations and polymorphisms in both RTS and LFS patient cells. A significant number of mutations and polymorphisms were common between RTS and LFS patients. These changes are associated with either aging and/or cancer, thereby indicating that the phenotypes associated with these syndromes may be due to deregulation of mitochondrial genome stability caused by the lack of RECQL4 and p53. SUMMARY: The biochemical mechanisms by which RECQL4 and p53 affect mtDNA replication have been elucidated. Resequencing of RTS and LFS patients' mitochondrial genome reveals common mutations indicating similar mechanisms of regulation by RECQL4 and p53.

RECQL4 is essential for the transport of p53 to mitochondria in normal human cells in the absence of exogenous stress.

Mutations in RECQL4 helicase are associated with Rothmund-Thomson syndrome (RTS). A subset of RTS patients is predisposed to cancer and is sensitive to DNA damaging agents. The enhanced sensitivity of cells from RTS patients correlates with the accumulation of transcriptionally active nuclear p53. We found that in untreated normal human cells these two nuclear proteins, p53 and RECQL4, instead colocalize in the mitochondrial nucleoids. RECQL4 accumulates in mitochondria in all phases of the cell cycle except S phase and physically interacts with p53 only in the absence of DNA damage. p53-RECQL4 binding leads to the masking of the nuclear localization signal of p53. The N-terminal 84 amino acids of RECQL4 contain a mitochondrial localization signal, which causes the localization of RECQL4-p53 complex to the mitochondria. RECQL4-p53 interaction is disrupted after stress, allowing p53 translocation to the nucleus. In untreated normal cells RECQL4 optimizes de novo replication of mtDNA, which is consequently decreased in fibroblasts from RTS patients. Wild-type RECQL4-complemented RTS cells show relocalization of both RECQL4 and p53 to the mitochondria, loss of p53 activation, restoration of de novo mtDNA replication and resistance to different types of DNA damage. In cells expressing Δ84 RECQL4, which cannot translocate to mitochondria, all the above functions are compromised. The recruitment of p53 to the sites of de novo mtDNA replication is also regulated by RECQL4. Thus these findings elucidate the mechanism by which p53 is regulated by RECQL4 in unstressed normal cells and also delineates the mitochondrial functions of the helicase.