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Background: Arteriography has been considered the 'Gold Standard' for the investigation of Peripheral arterial occlusive disease (PAOD). The development of Colour flow Doppler (CFD) has extended the scope of non-invasive assessment of chronic lower limb arterial disease. Aims: To evaluate and correlate the findings of CFD with arteriography as the gold standard, in PAOD of the lower extremities. Settings and Design: This prospective study was designed in the department of general surgery IGMC, HP. Patients were subjected to CFD scan followed by arteriography, to evaluate the aorto-iliac and femoropopliteal vessels. Materials and Methods: Thirty patients of PAOD formed the subjects and their affected lower limbs evaluated by CFD and arteriography, for localization and grading of lesion in the arteries, into normal/insignificant stenosis, significant stenosis and occlusion. The results were analyzed in a blind fashion in a total of 45 limbs comprising of 300 vascular segments. Statistical Analysis: Results were analyzed by two way contingency tables and kappa statistics. Results: CFD was able to identify 50 of the 59 (85%) lesions identified on arteriography. There was good statistical agreement and sensitivity of CFD ranged from, 80% to 100% and specificity from 93.9% to 100% in different arterial segments. Conclusions: CFD has grown from an ancillary diagnostic aid, to a critical component in the non-invasive diagnostic workup for patients with PAOD of the lower extremity, with the potential of displacing arteriography as the primary diagnostic imaging modality. [ABSTRACT FROM AUTHOR]

Acute urinary retention as a conversion symptom has received little attention in the literature and has been mostly considered as a diagnosis per exclusion. This is a case report of 20-year-old female who presented with acute retention of urine as a conversion symptom with strong psychological antecedents; she recovered completely by removing secondary gain, giving suggestions, and undergoing family counselling. [ABSTRACT FROM AUTHOR]

RAD51 is a highly conserved recombinase involved in the strand invasion/exchange of double-stranded DNA by homologous single-stranded DNA during homologous recombination repair. Although a majority of existing literature associates RAD51 with the pathogenesis of various types of cancer, recent reports indicate a role of RAD51 in maintenance of fertility. The present study reviews the role of RAD51 and its interacting proteins in spermatogenesis/oogenesis and additionally reports the findings from the molecular genetic screening of RAD51 135 G > C polymorphism in infertile cases and controls. Fifty-nine articles from PubMed and Google Scholar related to the reproductive role of RAD51 were reviewed. For case-control study, the PCR-RFLP method was used to screen the RAD51 135 G > C polymorphism in 201 infertile cases (100 males, 101 females) and 201 age- and gender-matched healthy controls (100 males, 101 females) from Punjab, North-West India. The review of literature shows that RAD51 is indispensable for spermatogenesis and oogenesis in animal models. Reports on the role of RAD51 in human fertility are limited, however it is involved in the pathogenesis of infertility in both males and females. Molecular genetic analyses in the infertile cases and healthy controls showed no statistically significant difference in the genotypic and allelic frequencies for RAD51 135 G > C polymorphism, even after segregation of the cases by type of infertility (primary/secondary). Therefore, the present study concluded that the RAD51 135 G > C polymorphism was neither associated with male nor female infertility in North-West Indians. This is the first report on RAD51 135 G > C polymorphism and infertility., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Faster vegetative growth and early maturity/harvest reduce plant life cycle time and are important agricultural traits facilitating early crop rotation. GA is a key hormone governing developmental transitions that determine growth speed in plants. An EAR-motif repressor, SlERF36 that regulates various growth transitions, partly through regulation of the GA pathway and GA levels, was identified in tomato. Suppression of SlERF36 delayed germination, slowed down organ growth and delayed the onset of flowering time, fruit harvest and whole-plant senescence by 10-15 days. Its over-expression promoted faster growth by accelerating all these transitions besides increasing organ expansion and plant height substantially. The plant life cycle and fruit harvest were completed 20-30 days earlier than control without affecting yield, in glasshouse as well as net-house conditions, across seasons and generations. These changes in life cycle were associated with reciprocal changes in expression of GA pathway genes and basal GA levels between suppression and over-expression lines. SlERF36 interacted with the promoters of two GA2 oxidase genes, SlGA2ox3 and SlGA2ox4, and the DELLA gene, SlDELLA, reducing their transcription and causing a 3-5-fold increase in basal GA 3 /GA 4 levels. Its suppression increased SlGA2ox3/4 transcript levels and reduced GA 3 /GA 4 levels by 30%-50%. SlERF36 is conserved across families making it an important candidate in agricultural and horticultural crops for manipulation of plant growth and developmental transitions to reduce life cycles for faster harvest., (© 2023 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

The present study deals with the metabolomic status of Ulva cells undergoing phase transition (vegetative, determination and differentiation) when exposed to different abiotic conditions. The objective was to study whether metabolite changes occurring during the phase transition reveal any commonality among differential abiotic conditions. The phase transition was followed through microscopic observations and 1 H NMR characterization at 0 h, 24 h, and 48 h after the incubation of the thallus under abiotic conditions, such as different salinities (20-35 psu), temperatures (20-35 °C), photoperiods (18 : 6, 12 : 12, and 6 : 18 D/N), light intensities (220, 350, and 500 μmol photons m -2 s -1 ), nitrate (0.05-0.2 g L -1 ) and phosphate (0.05-0.2 g L -1 ) concentrations. Microscopic analysis revealed the role of all abiotic conditions except variable salinity and phosphate concentration in phase transition. NMR analysis revealed that glucose increased in the determination phase [7.58 to 9.62 normalized intensity (AU)] and differentiation phase (5.85 to 6.41 AU) from 20 °C to 25 °C temperature. Coniferyl aldehyde increased in vegetative (5.79 to 6.83 AU) and differentiation (6.66 to 7.40 AU) phases from 20 °C to 30 °C temperature. The highest average (22.97) was found in photoperiod (average range = 0-122.91) and the highest SD (24.73) in salinity (SD range = 1.86-57.04) in region 9 (creatinine and cysteine) of the differentiation phase. A total of 30 metabolites were identified under the categories of sugars, amino acids, and aromatic compounds. The present study will aid in understanding the mechanisms underlying cell differentiation during reproduction. The result may serve as an important reference point for future studies, besides helping in controlling seedling preparation for commercial farming as well as the management of rapid green tide formation.

The combustion of mobil oil leads to the emission of toxic compounds in the environment. In this study, the aromatic and aliphatic hydrocarbon fractions present in a waste mobil oil collected from automobile market were comprehensively identified and their toxicity was evaluated using wheat grain. Lysinibacillus sphaericus strain IITR51 isolated and characterized previously could degrade 30-80% of both aliphatic and aromatic hydrocarbons in liquid culture. Interestingly, the strain IITR51 produced 627 mg/L of rhamnolipid biosurfactant by utilizing 3% (v/v) of waste mobil oil in the presence of 1.5% glycerol as additional carbon source. In a soil microcosm study by employing strain IITR51, 50-86% of 3-6 ring aromatic hydrocarbons and 63-98% of aliphatic hydrocarbons (C8 to C22) were degraded. Addition of 60 μg/mL rhamnolipid biosurfactant enhanced the degradation of both aliphatic and aromatic hydrocarbons from 76.88% to 61.21%-94.11% and 78.27% respectively. The degradation of mobil oil components improved the soil physico-chemical properties and increased soil fertility to 64% as evident by the phytotoxicity assessments. The findings indicate that strain IITR51 with degradation capability coupled with biosurfactant production could be a candidate for restoring hydrocarbon contaminated soils., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Abutilon indicum, widely found in India, Sri Lanka, and parts of America and Malaysia, is renowned for its rich bioactive compounds including alkaloids, flavonoids, and sesquiterpene lactones. Due to its diverse pharmacological potential, it has garnered significant attention in traditional medicine. In particular, the ethanolic leaf extract of Abutilon indicum (ELEAI) has demonstrated anti-inflammatory effects, notably targeting the 5-lipoxygenase enzyme pivotal in inflammatory responses., Objective: This study aimed to elucidate the impact of the ELEAI on proinflammatory marker gene expression induced by isoniazid (INH)., Methods: A total of 36 rats were systematically divided into six experimental groups. The control group received DMSO orally for the initial 30 days followed by distilled water for the subsequent 30 days. The INH group received a daily dose of INH (30 mg/kg b.w., i.p.) for 30 days and the rats were then sacrificed on day 30. The ELEAI (250 mg/kg) group was administered INH daily for 30 days, followed by daily post-treatment with ELEAI (250 mg/kg) for another 30 days. Similarly, the ELEAI (500 mg/kg) group received INH daily for 30 days, followed by daily post-treatment with ELEAI (500 mg/kg) for another 30 days. The silymarin (SIL) group was given INH daily for 30 days, followed by post-treatment with SIL at a dose of 100 mg/kg body weight daily for the subsequent 30 days. Finally, the ELEAI (500 mg/kg) alone group was administered distilled water orally for the first 30 days and then received ELEAI at a dose of 500 mg/kg b.w. orally once daily for the next 30 days., Results: Continuous INH exposure for a month led to a pronounced increase in proinflammatory genes like TNF-α, TGF-β, and NF-kB and a decrease in the IkB gene in rat liver tissues. Subsequent treatment with SIL (100 mg/kg) and ELEAI (250 and 500 mg/kg) post-INH exposure resulted in a marked decrease in proinflammatory genes and a surge in IkB expression., Conclusion: The findings suggest that the ELEAI exerts a dose-responsive influence on proinflammatory activities. Notably, A. indicum counteracts inflammation, especially that triggered by bradykinin and prostaglandins. The ELEAI showcases promising therapeutic potential, exhibiting both pro and anti-inflammatory properties and antiproliferative characteristics., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sunil et al.)

Cadmium (Cd) exposure to the animals including humans is reported as nephrotoxic compounds i.e., disturbing redox status (increase oxidative stress), mitochondrial dysfunction, renal cell death and altered transporters in the renal system. Hsp27 (a small heat shock protein) has been shown as one of the modulators in the renal dysfunction and increased against the Cd induced toxicity. However, no studies are reported on the genetic modulation of stress protein against the Cd-induced nephrotoxicity. The current study aimed to examine the protective role of hsp27 overexpression against the Cd-induced nephrotoxicity using Drosophila melanogaster as an animal model. D. melanogaster renal system includes nephrocytes and Malpighian tubules (MTs) that show the functional similarity with mammalian kidney nephron. Overexpression of the hsp27 was found to reduce the Cd induced oxidative stress, rescue cell death in MTs of Cd exposed D. melanogaster larvae. The rescued GSH level, NADPH level and glucose 6 phosphate dehydrogenase (G6PD) activity were also observed in the MTs of the Cd exposed organism. Function (efflux activity and fluid secretion rate) of the MTs was restored in Cd exposed hsp27 overexpressed larvae. Further, results were confirmed by restored brush border microvilli density and reduced uric acid level. Tissue specific knockdown of hsp27 developed Cd like phenotypes in MTs and the phenotypes enhanced in Cd exposed condition. The present study clearly shows the role of hsp27 overexpression in restoration of the MTs function and protection against the Cd induced renal toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Nervous system function rests on the formation of functional synapses between neurons. We have identified TRMT9B as a new regulator of synapse formation and function in Drosophila. TRMT9B has been studied for its role as a tumor suppressor and is one of two metazoan homologs of yeast tRNA methyltransferase 9 (Trm9), which methylates tRNA wobble uridines. Whereas Trm9 homolog ALKBH8 is ubiquitously expressed, TRMT9B is enriched in the nervous system. However, in the absence of animal models, TRMT9B's role in the nervous system has remained unstudied. Here, we generate null alleles of TRMT9B and find it acts postsynaptically to regulate synaptogenesis and promote neurotransmission. Through liquid chromatography-mass spectrometry, we find that ALKBH8 catalyzes canonical tRNA wobble uridine methylation, raising the question of whether TRMT9B is a methyltransferase. Structural modeling studies suggest TRMT9B retains methyltransferase function and, in vivo, disruption of key methyltransferase residues blocks TRMT9B's ability to rescue synaptic overgrowth, but not neurotransmitter release. These findings reveal distinct roles for TRMT9B in the nervous system and highlight the significance of tRNA methyltransferase family diversification in metazoans., (© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Aims: Isolation of phthalate esters (PAEs) degrading bacteria from a solid waste dumpsite could degrade many plasticizers efficiently and to investigate their degrading kinetics, pathways, and genes., Methods and Results: Based on their 16S rRNA gene sequence the strains were identified as Dietzia kunjamensis IITR165 and Brucella intermedia IITR166, which showed a first-order degradation kinetic model under lab conditions. The quantification of phthalates and their intermediate metabolites identification were done by using ultra-high-performance liquid chromatography (UHPLC) and gas chromatography-tandem mass-spectrometry (GC-MS/MS), respectively. Both the bacteria utilized >99% dibutyl phthalate at a high concentration of 100-400 mg L-1 within 192 h as monitored by UHPLC. GC-MS/MS revealed the presence of metabolites dimethyl phthalate (DMP), phthalic acid (PA), and benzoic acid (BA) during DBP degradation by IITR165 while monobutyl phthalate (MBP) and PA were identified in IITR166. Phthalate esters degrading gene cluster in IITR165 comprised two novel genes coding for carboxylesterase (dkca1) and mono-alkyl phthalate hydrolase (maph), having only 37.47% and 47.74% homology, respectively, with reported phthalate degradation genes, along with the terephthalate dioxygenase system (tphA1, A2, A3, and B). However, IITR166 harbored different gene clusters comprising di-alkyl phthalate hydrolase (dph_bi), and phthalate dioxygenase (ophA, B, and C) genes., Conclusions: Two novel bacterial strains, Dietzia kunjamensis IITR165 and Brucella intermedia IITR166, were isolated and found to efficiently degrade DBP at high concentrations. The degradation followed first-order kinetics, and both strains exhibited a removal efficiency of over 99%. Metabolite analysis revealed that both bacteria utilized de-methylation, de-esterification, and decarboxylation steps during degradation., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

Pollution from the oil industries and refineries has worsened various environmental compartments. In this study, indigenous oil degrading bacteria were isolated from crude oil obtained from an Oil and Natural Gas Corporation (ONGC) asset in Ankleshwar, Gujarat, India. Based on 16S rRNA phylogeny, they were identified as Pseudomonas boreopolis IITR108, Microbacterium schleiferi IITR109, Pseudomonas aeruginosa IITR110, and Bacillus velezensis IITR111. The strain IITR108, IITR109, IITR110, and IITR111 showed 80-89% and 71-78% degradation of aliphatic (C8-C40) and aromatic (4-5 ring) hydrocarbons respectively in 45 d when supplemented with 3% (v/v) waste crude oil. When compared to individual bacteria, the consortium degrades 93.2% of aliphatic hydrocarbons and 85.5% of polyaromatic hydrocarbons. It was observed that the total aliphatic and aromatic content of crude oil 394,470 μg/mL and 47,050 μg/mL was reduced up to 9617.75 μg/mL and 4586 μg/mL respectively in 45 d when consortium was employed. The rate kinetics analysis revealed that the biodegradation isotherm followed first order kinetics, with a linear correlation between concentration (hydrocarbons) and time intervals. The half-life of aliphatic (C8-C40) and aromatic hydrocarbons ranged from 200 to 453 h and 459-714 h respectively. All the bacteria efficiently produced catabolic enzymes such as alkane monooxygenase, alcohol dehydrogenase, and lipase during the degradation of crude oil. These findings indicated that the bacterial consortium can be a better candidate for bioremediation and reclamation of aliphatic and aromatics hydrocarbon contaminated sites., Competing Interests: Declaration of competing interest The authors declare that they have no known financial or personal conflict for the publication of this manuscript., (Copyright © 2023. Published by Elsevier Ltd.)

Benzodiazepines can make victims more docile, they are frequently used in drug-facilitated crimes, such as robberies and sexual assaults. Therefore, it is essential to develop techniques for determining whether these chemicals are present in relation with illegal activity is crucial. Therefore, to determine the presence of five benzodiazepines (alprazolam, clonazepam, diazepam, lorazepam, and oxazepam) in water, alcoholic beverages, and non-alcoholic beverages, a simple and direct, miniaturized, and effective vortex assisted ultrasound based microextraction using solidification of floating organic droplets (VAUS-ME-SFO) in combination with LC-MS/MS was developed. 1-Undecanol and acetonitrile, respectively, served as the extractant and disperser solvents. Many other parameters affect the efficiency of the developed analytical procedure VAUS-ME-SFO/LC-MS/MS. These parameters were optimized using Plackett Burman Design and Central Composite Design to obtain reliable results. The optimum conditions for the extraction were: 10.0 mL of sample; 180 μL acetonitrile, as a dispersive solvent; 200 μL of 1-undecanol, as an extraction solvent; pH 7; 105 s of vortex agitation; 120 s of ultrasonication application and 3 min of centrifugation at 7000 rpm. The benzodiazepines were separated by a chromatographic separation technique carried out by a UPLC system consisting of a binary mobile phase. The solvent system comprises of 0.1% Formic acid in Milli-Q (Solvent A) and 0.1% Formic acid in ACN (Solvent B) with a gradient flow of 3.5 min total analysis time. Under the optimized conditions, the calibration curve was studied in the range of 0.124-7.810 ng mL -1 . The regression correlation coefficient (R 2 ) value of all targeted analytes ranges from 0.993 to 0.999. The LOD and LOQ of VAUS-ME-SFO methods using LC-MS/MS analysis range from 0.316 to 0.968 ng mL -1 and 1.055-3.277 ng mL -1 respectively. The repeatability within a day varied from 0.6 to 3.5%, and the reproducibility across days varied from 2.2 to 6.3%. The recoveries ranges for water, alcoholic and non-alcoholic beverages from 70.77 to 114.53%, 63.20-102.21% and 66.23-113.28% respectively. Further, the degradation kinetics was studied to establish the half-life of each targeted analyte in the matrix undertaken in the study. The water samples were classified based on their BDZs residues. This implies that the more health care and anthropogenic activity, the more the BDZs residue will be in water samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

β-triketone herbicides have been efficiently employed as an alternate to atrazine. Triketones are 4-hydroxyphenylpyruvate dioxygenase (HPPD) enzyme inhibitors and exposure is reported to cause significant increase in plasma tyrosine levels. In this study, we have employed a non-target organism Caenorhabditis elegans to determine the impact of β-triketone exposures at recommended field doses (RfD). Our results indicate sulcotrione and mesotrione, negatively influence the survival, behavior, and reproduction of the organism at RfD. Additionally, we have traced the parallels regarding the impact of triketones on the tyrosine metabolism pathway, in C. elegans to those in mammalian models, wherein the expression of the tyrosine metabolism pathway genes are altered, directly influencing tyrosine catabolism leading to significant tyrosine accumulation in exposed organism. Further, we investigated the impact of sulcotrione and mesotrione exposure on fat deposition (triglyceride levels, Oil-Red-O staining and lipidomics) and the fatty acid metabolism pathway. In the exposed worms, the expression of enlongases and fatty acid desaturases were up-regulated along with an increase in the levels of triglycerides. Thus, the data indicates a positive association of β-triketone exposure to mis-regulation of the fatty acid metabolism pathway genes leading to fat accumulation in worms. Therefore, β-triketone might be a potential obesogen., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Movement disorder (MD) is an important manifestation of neurologic Wilson disease (NWD), but there is a paucity of information on dopaminergic pathways. We evaluate dopamine and its receptors in patients with NWD and correlate the changes with MD and MRI changes. Twenty patients with NWD having MD were included. The severity of dystonia was assessed using BFM (Burke-Fahn-Marsden) score. The neurological severity of NWD was categorized as grades I to III based on the sum score of 5 neurological signs and activity of daily living. Dopamine concentration in plasma and CSF was measured using liquid chromatography-mass spectrometry, and D1 and D2 receptor expression at mRNA by reverse transcriptase polymerase chain reaction in patients and 20 matched controls. The median age of the patients was 15 years and 7 (35%) were females. Eighteen (90%) patients had dystonia and 2 (10%) had chorea. The CSF dopamine concentration (0.08 ± 0.02 vs 0.09 ± 0.017 pg/ml; p = 0.42) in the patients and controls was comparable, but D2 receptor expression was reduced in the patients (0.41 ± 0.13 vs 1.39 ± 1.04; p = 0.01). Plasma dopamine level correlated with BFM score (r = 0.592, p < 0.01) and D2 receptor expression with the severity of chorea (r = 0.447, p < 0.05). The neurological severity of WD correlated with plasma dopamine concentration (p = 0.006). Dopamine and its receptors were not related to MRI changes. The central nervous system dopaminergic pathway is not enhanced in NWD, which may be due to structural damage to the corpus striatum and/or substantia nigra., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Indole is a nitrogenous heterocyclic aromatic pollutant often detected in various environments. An efficient indole degrading bacterium strain IITR89 was isolated from River Cauvery, India, and identified as Alcaligenes faecalis subsp. phenolicus. The bacterium was found to degrade ~ 95% of 2.5 mM (293.75 mg/L) of indole within 18 h utilizing it as a sole carbon and energy source. Based on metabolite identification, the metabolic route of indole degradation is indole → (indoxyl) → isatin → (anthranilate) → salicylic acid → (catechol) → (Acetyl-CoA) → and further entering into TCA cycle. Genome sequencing of IITR89 revealed the presence of gene cluster dmpKLMNOP, encoding multicomponent phenol hydroxylase; andAbcd gene cluster, encoding anthranilate 1,2-dioxygenase ferredoxin subunit (andAb), anthranilate 1,2-dioxygenase large subunit (andAc), and anthranilate 1,2-dioxygenase small subunit (andAd); nahG, salicylate hydroxylase; catA, catechol 1,2-dioxygenase; catB, cis, cis-muconate cycloisomerase; and catC, muconolactone D-isomerase which play an active role in indole degradation. The findings strongly support the degradation potential of strain IITR89 and its possible application for indole biodegradation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

DNA double-strand break (DSB) repair is initiated by DNA end resection. CtIP acts in short-range resection to stimulate MRE11-RAD50-NBS1 (MRN) to endonucleolytically cleave 5'-terminated DNA to bypass protein blocks. CtIP also promotes the DNA2 helicase-nuclease to accelerate long-range resection downstream from MRN. Here, using AlphaFold2, we identified CtIP-F728E-Y736E as a separation-of-function mutant that is still proficient in conjunction with MRN but is not able to stimulate ssDNA degradation by DNA2. Accordingly, CtIP-F728E-Y736E impairs physical interaction with DNA2. Cellular assays revealed that CtIP-F728E-Y736E cells exhibit reduced DSB-dependent chromatin-bound RPA, impaired long-range resection, and increased sensitivity to DSB-inducing drugs. Previously, CtIP was shown to be targeted by PLK1 to inhibit long-range resection, yet the underlying mechanism was unclear. We show that the DNA2-interacting region in CtIP includes the PLK1 target site at S723. The integrity of S723 in CtIP is necessary for the stimulation of DNA2, and phosphorylation of CtIP by PLK1 in vitro is consequently inhibitory, explaining why PLK1 restricts long-range resection. Our data support a model in which CDK-dependent phosphorylation of CtIP activates resection by MRN in S phase, and PLK1-mediated phosphorylation of CtIP disrupts CtIP stimulation of DNA2 to attenuate long-range resection later at G2/M., (© 2023 Ceppi et al.; Published by Cold Spring Harbor Laboratory Press.)

In recent years, special attention has been given to emission research that led to the deposition of toxicants from road traffic. Thus, it is imperative to focus on heavy metal (HM) stressors in food items, their source contribution, and health risk assessment providing insight into their spatial role at the population level. In this study, heavy metal in the street vended noodles was studied while correlating the quality of noodle with different environmental origins. The samples were prepared using acid digestion and analysed by flame atomic absorption spectrophotometer, except Hg which was analysed by direct mercury analyser. The results showed that some heavy metals like Cr, Pb, Mn, Cd, and Hg exceed their permissible limits established by the international legislation for food products. In the noodle samples, the concentration of heavy metal ranged from < 0.1 to 0.904 mg/kg for Pb, < 0.09 to 0.843 mg/kg for Ni, < 0.004 to 0.201 mg/kg for Cd, < 0.0001 to 0.004 mg/kg for Hg, < 0.01 to 1.388 mg/kg for Cu, < 0.015 to 8.049 mg/kg for Mn, and < 0.02 to 16.514 mg/kg for Cr. Noodle samples vended on high traffic density streets are directly associated with increased HM content due to atmospheric deposition from the surrounding. Source apportionment study determines that HM contamination belongs to the same source of origin, except Cr. Based on the cluster analysis, these samples fall into three major groups that were further validated by the canonical discriminant function. Health risk prediction by Monte Carlo simulation revealed an elevated non-carcinogenic health hazard risk to consumers with a hazard index (HI) shift from 71 to 75%. Health hazard analysis showed that consumers of high traffic density street vended food are at higher risk of developing health-related issues. This study is important to evaluate the health risk of the population exposed to heavy metals due to ingestion of street vended food., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Low-cost alginate gels of activated carbons were prepared, which were derived from the peels of banana and sweet lime. The synthesized carbon was activated and immobilized on alginate, producing its gel. These gels were categorized according to their methods of drying, in which air drying, freeze drying, and supercritical drying led to the formation of xerogels, cryogels, and aerogels, respectively. The gels were used for adsorption of heavy metals from their aqueous solution. The heavy metals that were targeted for removal were Pb(II), Cd(II), Cr(VI), As(III), and Hg(II). Among all the adsorbents, the alginate cryogel of sweet lime-derived activated carbon (SLACC) showed the highest removal percentage of heavy metals, and thus, it was used for batch study. The adsorption of heavy metals by SLACC was checked at different times, pH values, adsorbent doses, temperatures, and adsorbate concentrations. The study revealed that the pseudo-second-order model best described the kinetic study, while the adsorption followed the Freundlich isotherm. SLACC showed maximum adsorption capacities ( q cal ) of 3.71, 4.22, 20.04, 7.31, and 4.37 mg/g for Cr, Cd, Pb, As, and Hg, respectively, when 20 mg of SLACC was used for the removal of 4 ppm concentration of the targeted heavy metals from their 20 mL solution. Based on the thermodynamic study, it was found that the adsorption was spontaneous and exothermic. Furthermore, the adsorbent was also used on real water samples and showed up to 90% removal efficiency for these targeted heavy metals. SLACC was regenerated with 0.1 M ethylenediaminetetraacetic acid (EDTA) solution and reused for five cycles, in which the percentage removal of heavy metals was more than 50% till the fourth cycle. Furthermore, the leaching study showed that no toxic elements had leached from SLACC into water, making it a safe adsorbent., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

In the present study, effect of exposure of bisphenol A (BPA) and combined exposure of BPA + HSD has been investigated on the glucose homeostasis and associated renal complications in Drosophila. Exposure of 1.0 mM BPA alone induced type 2 diabetes like condition (T2D) in adult male D. melanogaster via oxidative stress. Elevated TGF-β signaling was evident by increased expression of baboon (babo) in BPA exposed organism that stimulated the modulation of extracellular matrix (ECM) component collagen IV resulting in the fibrosis of the Malpighian tubules (MTs). Combined exposure of BPA + HSD (high sucrose diet) resulted in the increased magnitude of T2D and MTs dysfunction parameters. Taken together, the study illustrates that BPA has diabetogenic potential in exposed Drosophila that caused adverse effects on their MTs and combined exposure with BPA and HSD could aggravate the renal tubular dysfunction. The study further suggests the use of Drosophila model to study the environmental chemicals induced diabetes mediated renal dysfunction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This research article aims to establish an easy and well-defined analytical method for detection and quantification of multiclass pesticides in Gomti river water samples because the increased agricultural activities, industrialization, and urbanization had increased the presence of pesticides in the ecosystem which causes the depletion of water quality making it a global concern. The analytical method, vortex-assisted ultrasonication-based dispersive liquid-liquid microextraction-solidification of floating organic droplets (VAUS-DLLME-SFO) was optimized using one parameter at a time approach which gave the recovery between 69.45 and 114.15%, limit of detection (LOD), and limit of quantification (LOQ) 0.0011-0.0111 µg/L and 0.0033-0.0368 µg/L, respectively, and RSD in the range of 0.75-1.29 which shows sensitivity and accuracy better than earlier reported methods. The data obtained were subjected to measurement uncertainty, risk assessment, and multivariate statistical analysis to establish the robustness of the developed analytical method. The measurement uncertainty found was concluded to be in the acceptable range for analytical results. Furthermore, the real samples were analyzed and the associated value of the risk quotient was found to be less than 1, except for aquatic invertebrates, establishing the fact that the current concentration of pesticides has no such negative threat to flora and fauna. The possible source of pesticides in the Gomti river system was established by multivariate analysis. It was thus concluded that anthropogenic activity is responsible for the variable concentration of pesticides found in the sample., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Symbiotic interactions play a crucial role in the phosphate (Pi) nutrient status of the host plant and offer resilience during biotic and abiotic stresses. Despite a competitive behavior of arsenic (AsV) with Pi, Serendipita indica association promotes plant growth by reducing arsenic bioavailability in the rhizosphere. Reduced arsenic availability is due to the adsorption, accumulation, and precipitation of arsenic in the fungus. The present investigation focused on the fitness and performance of Pi acquisition and utilization in S. indica for growth and metabolism under arsenic stress. The fungus accumulates a massive amount of arsenic up to 2459.3 ppm at a tolerable limit of arsenic supply (1 mM) with a bioaccumulation factor (BAF) 32. Arsenic induces Pi transporter expression to stimulate the arsenic acquisition in the fungus. At the same time, Pi accumulation was also enhanced by 112.2 times higher than the control with an increase in poly-P (polyphosphate) content (6.69 times) of the cell. This result suggests arsenic does not hamper poly-P storage in the cell but shows a marked delocalization of stored poly-P from the vacuoles. Furthermore, an enhanced exopolyphosphatase activity and poly-P storage during arsenic stress suggest induction of cellular machinery for the utilization of Pi is required to deal with arsenic toxicity and competition. However, at high arsenic supply (2.5 and 5 mM), 14.55 and 22.07 times reduced Pi utilization, respectively, was observed during the Pi uptake by the fungus. The reduction of Pi uptake reduces the cell growth and biomass due to competition between arsenic and phosphate. The study suggests no negative impact of arsenic on the Pi acquisition, storage, and metabolism in symbiotic fungus, S. indica, under environmental arsenic contamination., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Various immune cells are known to participate in combating infection. Regulatory B cells represent a subset of B cells that take part in immunomodulation and control inflammation. The immunoregulatory function of regulatory B cells has been shown in various murine models of several disorders. In this study, a comparable IL-10 competent B-10 cell subset (regulatory B cells) was characterized during lethal and non-lethal infection with malaria parasites using the mouse model. We observed that infection of Balb/c mice with P. yoelii I 7XL was lethal, and a rapid increase in dynamics of IL-10 producing B220 + CD5 + CD1d + regulatory B cells over the course of infection was observed. However, animals infected with a less virulent strain of the parasite P. yoelii I7XNL attained complete resistance. It was observed that there is an increase in the population of regulatory B cells with an increase of parasitemia; however, a sudden drop in the frequency of these cells was observed with parasite clearance. Adoptive transfer of regulatory B cells to naïve mice followed by infection results in slow parasite growth and enhancement of survival in P. yoelii 17XL (lethal) infected animals. Adoptively transferred regulatory B cells also resulted in decreased production of pro-inflammatory cytokine (IFN-γ) and enhanced production of anti-inflammatory cytokine (IL-10). It infers that these regulatory B cells may contribute in immune protection by preventing the inflammation associated with disease and inhibiting the parasite growth.

Incessant production, pervasive applications in different fields, and eventually unintended exposure of cobalt oxide nanoparticles (Co3O4 NPs) lead to rise in their toxicity studies toward human health. However, the information regarding the potential toxicity mechanisms of Co3O4 NPs especially genotoxicity is still sparse with missing interconnections. So far, only solitary reports on Co3O4 NPs are at hand, bearing witness to reactive oxygen species (ROS)-mediated DNA damage in lung cells. To address this, we evaluated the Co3O4 NP-induced cytotoxic and genotoxic potential in Chinese hamster lung fibroblast cell line (V79). Our preliminary results demonstrate that Co3O4 NPs at concentrations of 20-100 µg/ml induced moderate mortality after 24-h exposure. However, these low concentrations caused a significant reduction in various organelles' activity in a concentration-dependent manner. Mitochondrial activity and membrane potential were found to be compromised due to NP exposure in a concentration-dependent manner. The study affirms that Co3O4 NPs inhibited lysosomal activity in V79 cells. In addition to this, Co3O4 NPs are also found to stimulate free oxygen radical generation. Genotoxicity studies revealed a potent and dose-dependent effect of non-cytotoxic concentrations of Co3O4 NPs in the induction of DNA lesions. Interestingly, N-acetylcysteine, a free oxygen radical scavenger (5, 10 mM, pretreatment) inhibited the progression of free oxygen radicals and induction of Co3O4 NP-mediated DNA lesions. This suggests the ROS-mediated genotoxic potential of Co3O4 NPs., (© The Author(s) 2022. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Regulatory T cells are known to play a key role to counter balance the protective immune response and immune mediated pathology. However, the role of naturally occurring regulatory cells CD4 + CD25 + Foxp3 + in malaria infection during the disease pathogenesis is controversial. Beside this, ICOS molecule has been shown to be involved in the development and function of regulatory T cell enhance IL-10 production. Therefore, possible involvement of the ICOS dependent regulatory CD4 + ICOS + Foxp3 + T cells in resistance/susceptibility during malaria parasite is explored in this study., Methods: 5 × 10 5 red blood cells infected with non-lethal and lethal parasites were inoculated in female Balb/c mice by intra-peritoneal injection. Infected or uninfected mice were sacrificed at early (3rd day post infection) and later stage (10th day post infection) of infection. Harvested cells were analysed by using flow cytometer and serum cytokine by Bioplex assay., Results: Thin blood films show that percentages of parasitaemia increases with disease progression in infections with the lethal malaria parasite and mice eventually die by day 14th post-infection. Whereas in case of non-lethal malaria parasite, parasitaemia goes down by 7th day post infection and gets cleared within 13th day. The number of CD4 + ICOS + T cells increases in lethal infection with disease progression. Surprisingly, in non-lethal parasite, ICOS expression decreases after day 7th post infection as parasitaemia goes down. The frequency of CD4 + ICOS + FoxP3 + Tregs was significantly higher in lethal parasitic infection as compared to the non-lethal parasite. The level of IL-12 cytokine was remarkably higher in non-lethal infection compared to the lethal infection. In contrast, the level of IL-10 cytokines was higher in lethal parasite infection compared to the non-lethal parasite., Conclusion: Taken together, these data suggest that lethal parasite induce immunosuppressive environment, protecting from host immune responses and help the parasite to survive whereas non-lethal parasite leads to low frequencies of Treg cells seldom impede immune response that allow the parasite to get self-resolved., (© 2022. The Author(s).)

Mesenchymal stem cells (MSCs) are self-renewing, multi-potent heterogeneous stem cells that display strong tissue protective and restorative properties by differentiating into cells of the mesodermal lineages. In addition to multi-lineage differentiation capacity, MSCs play important roles in regulating immune responses, inflammation, and tissue regeneration. MSCs play a role in the outcome of the pathogenesis of several infectious diseases. A unique subset of MSCs accumulates in secondary lymphoid organs during malaria disease progression. These MSCs counteract the capacity of malaria parasites to subvert activating co-stimulatory molecules and to regulate expression of negative co-stimulatory molecules on T lymphocytes. Consequently, MSCs have the capacity to restore the functions of CD34 + haematopoietic cells and CD4 + and CD8 + T cells during malaria infection. These observations suggest that cell-based therapeutics for intervention in malaria may be useful in achieving sterile clearance and preventing disease reactivation. In addition, MSCs provide host protection against malaria by reprogramming erythropoiesis through accelerated formation of colony-forming-units-erythroid (CFU-E) cells in the bone marrow. These findings suggest that MSCs are positive regulators of erythropoiesis, making them attractive targets for treatment of malarial anemia. MSC-based therapies, unlike anti-malarial drugs, display therapeutic effects by targeting a large variety of cellular processes rather than a single pathway. In the present review we focus on these recent research findings and discuss clinical applications of MSC-based therapies for malaria., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sewage sludge (SS) is an abundantly available feedstock, which is generally considered as potential threat to human health and environment. Its utilization in any process would be of great help for environmental sustainability. Accordingly, this work aimed to prepare and characterize the sewage sludge biochar (SSB) at temperatures, i.e. (500, 450, 400, and 350 °C), and further analyze the available nutrients and contaminants as well as agri application potential. The results indicated that the total nitrogen (TN), electrical conductivity (EC), and total organic carbon (TOC) content in SSBs decreased with increasing pyrolysis temperature. The overall concentration of polycyclic aromatic hydrocarbons (PAHs) in SSBs was substantially lower (1.8-9.7-fold depending on pyrolysis temperature) than in SS. Pyrolysis of SS enriched the heavy metals content in SSBs and the relative enrichment factor (RE) factor varied between 1.1 and 2.1 depending on the pyrolysis temperature. Furthermore, compared to SS, the leaching rate of heavy metals was significantly decreased in SSBs (1.1-100-fold depending on the pyrolysis temperature) and the pyrolysis temperature of 400-450 °C prevented the Ni, Pb, Cr, and Zn leaching in SSB. The total PAH and heavy metals content in biochars were below the control standard for land application. Finally, testing of the growth-promoting effect of biochar extracts on fenugreek plants revealed that SSB prepared at 350 °C significantly stimulated the root and shoot length of 5-days old seedlings. This study provides important data for potential environmental risks of SSB applications., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Cerebral Salt wasting (CSW) is common in Tuberculous Meningitis (TBM) and is suggested to be due to sympathetic dysregulation of renal blood supply but has not been proven., Objective: To evaluate plasma Catecholamines in TBM patients with CSW and correlate with the markers of stress., Materials and Methods: The diagnosis of TBM was based on clinical, CSF and MRI criteria. Catecholamines level was measured by LC-MS on admission, at the time of hyponatremia and on correction of hyponatremia. Catecholamine levels were correlated with clinical and laboratory markers of stress, hyponatremia and severity of CSW using pre-defined criteria., Results: There were 24 patients with TBM (12 with CSW) and 12 controls. The median age of patients was 31 (18-75) years and 12 (50 %) were females. TBM patients with CSW had significantly higher levels of catecholamines compared to controls (p < 0.001). TBM patients with CSW had higher levels of norepinephrine than those without CSW (p = 0.034). Sequential studies revealed that dopamine and epinephrine increased at the time of hyponatremia and declined on its correction. Severity of TBM was related to dopamine (p = 0.04) and severity of CSW was related to epinephrine (p = 0.016)., Conclusion: CSW in TBM seems to be related to catecholamine dysregulation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Malaria remains a major public health problem worldwide. The immune mechanisms that mediate protection against malaria are still unclear. Previously, we reported that mesenchymal stem cells (MSCs) play a critical role in host protection against malaria by altering the dynamic balance of T regulatory cells and effector T cells producing inflammatory cytokines. Here, we report that MSCs reprogram haematopoiesis in primary (bone marrow) and secondary (spleen) lymphoid organs to provide host protection against malaria. Adoptive transfer of MSCs from malaria-infected mice to naïve recipient mice that were subsequently infected with malaria parasites dramatically accelerated the formation of colony-forming units-erythroid cells in the bone marrow. Adoptively transferred MSCs also induced expression of the key erythroid cell differentiation factor GATA-1 in the spleen of recipient animals. Interestingly, we further observed a subtle increase in the CD34 + hematopoietic stem and progenitor cells in lymphoid organs, including spleen and lymph nodes. Infusion of MSCs also enhanced T cell proliferation, resulting in increased numbers of both CD4 + and CD8 + T cells in the spleen. MSCs also inhibited the induction of the negative co-stimulatory receptor programmed death-1 by T cells in recipient animals upon infection with malaria parasites. Taken together, our findings suggest that MSCs play a critical role in host protection against malaria infection by modulating erythropoiesis and lymphopoiesis.

Hepatocellular carcinoma is the second leading cause of cancer-related mortality worldwide. Lagerstroemia speciosa Pers. (Lythraceae) commonly known as Banaba has been used in different forms in traditional medicinal systems for treating various diseases which include diabetes and obesity. In this study, we investigated the cytotoxic potential of ethanolic Banaba leaf extract (EBLE) in HepG2 cells. The phytochemical analysis of EBLE was performed by HPTLC. HepG2 cells were treated with EBLE at 25, 50, 100, and 150 μg/mL concentrations, and cytotoxicity was evaluated by MTT assay. Oxidative stress was assessed by the evaluation of lipid peroxidation, superoxide dismutase, and reduced glutathione. Apoptosis-related morphology was investigated by acridine orange and ethidium bromide (AO/EB) dual staining. Mitochondrial membrane potential (ΔΨm) was evaluated by JC-1 staining. Apoptosis-related marker genes were evaluated by qPCR. HPTLC analysis confirmed the presence of corosolic acid (12.87 μg/mg), berberine (3.19 μg/mg), and gallic acid (2.94 μg/mg) in EBLE. EBLE treatments caused significant and concentration-dependent cytotoxicity and oxidative stress in HepG2 cells. Dual staining with AO/EB confirmed membrane distortion and nuclear chromatin condensation upon EBLE treatments. JC-I staining revealed the loss of ΔΨm. Furthermore, at a molecular level, EBLE treatments interfere with Bax/Bcl-2 homeostasis and induced the pro-apoptotic marker genes such as cytochrome c, Apaf-1, and caspases 9 and 3. EBLE treatments caused cytotoxicity in HepG2 cells, and this could be due to the induction of oxidative stress and apoptosis via the intrinsic or mitochondrial pathway., (© 2020 Wiley Periodicals LLC.)

Oncogene activation during tumorigenesis generates DNA replication stress, a known driver of genome rearrangements. In response to replication stress, certain loci, such as common fragile sites and telomeres, remain under-replicated during interphase and subsequently complete locus duplication in mitosis in a process known as 'MiDAS'. Here, we demonstrate that RTEL1 (regulator of telomere elongation helicase 1) has a genome-wide role in MiDAS at loci prone to form G-quadruplex-associated R-loops, in a process that is dependent on its helicase function. We reveal that SLX4 is required for the timely recruitment of RTEL1 to the affected loci, which in turn facilitates recruitment of other proteins required for MiDAS, including RAD52 and POLD3. Our findings demonstrate that RTEL1 is required for MiDAS and suggest that RTEL1 maintains genome stability by resolving conflicts that can arise between the replication and transcription machineries.

Parabens, the alkyl esters of p-hydroxybenzoic acid such as methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), butylparaben (BuP) are used as a preservative in food, personal care products (PCPs), and pharmaceuticals, due to their antimicrobial properties. Parabens are continuously released into the environment, during washout of PCPs, disposal of industrial waste from the pharmaceutical and paper industries. Parabens have been detected in the indoor dust, wastewater stream, surface water of rivers, and the marine system. Recent eco-toxicological data and the environmental presence of parabens, has raised concerns regarding the safety and health of environment/humans. Thus, to further understand the toxicity of parabens, the present study was carried out in the soil nematode and well established biological model organism Caenorhabditis elegans. In the present study, LC 50 of MeP, EtP, PrP and BuP for 72 h exposures from L1 larva to adult stage was found to be 278.1, 217.8, 169.2, and 131.88 μg/ml, respectively. Further exposure to 1/5th of LC 50 of parabens yielded an internal concentration ranging from 1.67 to 2.83 μg/g dry weight of the organism. The toxicity of parabens on the survival, growth, behavior, and reproduction of the C. elegans was found in the order of BuP > PrP > EtP > MeP. Worms exposed to parabens show significant down-regulation of vitellogenin genes, high levels of reactive oxygen species and anti-oxidant transcripts, the latter being concordant with nuclear localization of DAF-16 and up-regulation of HSF-1 and SKN-1/Nrf. Hence, parabens caused endocrine disruption, oxidative stress and toxicity in C. elegans at environment relevant internal concentration of parabens., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The ATR kinase is a master regulator of the cellular response to DNA replication stress. Activation of ATR relies on dual pathways involving the TopBP1 and ETAA1 proteins, both of which harbor ATR-activating domains (AADs). However, the exact contribution of the recently discovered ETAA1 pathway to ATR signaling in different contexts remains poorly understood. Here, using an unbiased CRISPR-Cas9-based genome-scale screen, we show that the ATR-stimulating function of ETAA1 becomes indispensable for cell fitness and chromosome stability when the fidelity of DNA replication is compromised. We demonstrate that the ATR-activating potential of ETAA1 is controlled by cell cycle- and replication stress-dependent phosphorylation of highly conserved residues within its AAD, and that the stimulatory impact of these modifications is required for the ability of ETAA1 to prevent mitotic chromosome abnormalities following replicative stress. Our findings suggest an important role of ETAA1 in protecting against genome instability arising from incompletely duplicated DNA via regulatory control of its ATR-stimulating potential., (© 2019 Achuthankutty et al.)

The aim of this survey-based study was to recognize professional determinants that account for variations in the level of orthodontic services provided and which distinguish providers and nonproviders of orthodontic services. Multiple regression analysis revealed that four practitioner characteristics explained 43% of the variance in the number of orthodontic patients treated. Dentists who treated more orthodontic patients (1) treated more general practice patients, (2) frequently used multiple sources to keep up to date in orthodontics, (3) perceived their patient base to contain more children, and (4) were likely to have attended an orthodontic course. The null hypothesis that selected characteristics of dentists providing orthodontic services were no different from those of dentists not providing orthodontic services was rejected. The provision of orthodontic services was associated with a higher level of continuing orthodontic education and treating more general practice patients, especially children., Competing Interests: There are no conflicts of interest.

Aim: The aim of the present study was to evaluate the radiographic length of velum (LV), width of velum (WV), velum angle (AV), depth of pharynx (PD), Need's ratio (NR), inclination angle (AI) in different morphological types of soft palate according to growth patterns in skeletal class I individuals., Methodology: 80 pretreatment lateral cephalograms of patients with skeletal class I malocclusion (ANB 2--4°) were divided on basis of six types of soft palate and further into three subgroups according to growth pattern and evaluation of LV, WV, angle with the palatal plane, and NR was done. Kruskal--Wallis test was used for the comparison between the groups., Results: Statistically significant difference was verified among all groups for measurement of NR. The highest NR was seen in Crook type of soft palate (mean 0.9). Similarly, the vertical growth pattern in all the six types of soft palate exhibited a higher NR than the average and horizontal growth pattern group; the highest being exhibited by vertical group in type VI (crook shaped). Velopharyngeal insufficiency is directly related to NR., Conclusion: Vertical growth pattern has the highest susceptibility to velopharyngeal insuffiency and speech and sleep apnea disorders., Competing Interests: There are no conflicts of interest.

Unresolved G-quadruplex (G4) DNA secondary structures impede DNA replication and can lead to DNA breaks and to genome instability. Helicases are known to unwind G4 structures and thereby facilitate genome duplication. Escherichia coli UvrD is a multifunctional helicase that participates in DNA repair, recombination and replication. Previously, we had demonstrated a novel role of E. coli UvrD helicase in resolving G4 structures. Mycobacterium tuberculosis genome encodes two orthologs of E. coli UvrD helicase, UvrD1 and UvrD2. It is unclear whether UvrD1 or UvrD2 or both helicases unwind G4 DNA structures. Here, we demonstrate that M. tuberculosis UvrD1 and UvrD2 unwind G4 tetraplexes. Both helicases were proficient in resolving previously characterized tetramolecular G4 structures in an ATP hydrolysis and single-stranded 3'-tail-dependent manner. Notably, M. tuberculosis UvrD1 and UvrD2 were efficient in unwinding G4 structures derived from the potential G4 forming sequences present in the M. tuberculosis genome. These data suggest an extended role for M. tuberculosis UvrD1 and UvrD2 helicases in resolving G4 DNA structures and provide insights into the maintenance of genome integrity via G4 DNA resolution., (© 2019 Federation of European Biochemical Societies.)

Abscission is the final step of cell division when the cytokinetic furrow ingresses completely, leading to midbody formation and plasma membrane fission [1]. In human cells, the Aurora-B-driven abscission checkpoint delays cytokinesis until any residual chromatin spanning the midbody is removed [2-5]. If this does not occur efficiently, uneven segregation of daughter genomes can occur. The mechanism by which the abscission checkpoint becomes satisfied to permit cytokinesis is poorly defined. Here, we identify RIF1 and its binding partner, protein phosphatase 1 (PP1), as being critical for regulation of abscission timing in human cells. We show that RIF1 promotes cytokinesis through recruitment of PP1 to the midbody, which then counteracts Aurora B kinase activity, leading to dephosphorylation of a regulator of abscission timing, CHMP4C [6-10]. Although RIF1 binds to unresolved DNA bridges that persist into telophase [11], we show that this cytokinetic function of the RIF1-PP1 axis is not limited to instances where cell division is perturbed by the presence of bridges. Nevertheless, we show that altering the balance of the opposing Aurora B kinase and PP1 phosphatase activities makes cells unresponsive to DNA bridges and sensitizes cells to agents that induce bridge formation. Our data define a new mechanism for regulation of abscission timing and emphasize how antagonism between kinases and phosphatases is a widespread mechanism for determining the timing of mitotic transactions. Because cancer cells experiencing oncogene-induced replication stress generate excessive mitotic DNA bridging [12], targeting this new regulatory pathway could be a promising therapeutic strategy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Trigonella foenum graecum L. is a dietary herb used in traditional medicine system. In this study, we investigated the cytotoxicity, antitumor, antimetastatic and antiangiogenic effect of the steroidal compound, ethyl iso-allocholate isolated from T. foenum graecum L. seeds against A549 lung cancer cells in vitro and in vivo. Among all the isolated compounds, the ethyl iso-allocholate rendered the highest cytotoxicity potential. It showed least percentage cell viability in trypan blue assay and lowest nuclei count in hoechst staining. The caspase glo assay and western blot analysis showed the significant caspase 3 cleavage, indicating caspase dependent apoptosis. Consistent with the in vitro data, ethyl iso-allocholate showed highest percentage tumor growth inhibition i.e. 80 ± 5% in zebrafish, equivalent to doxorubicin. It significantly reduced angiogenesis to 5 ± 0.8% (**P < 0.01), compared to negative control group which was 60 ± 2%. The ethyl iso-allocholate showed 55 ± 3% inhibition in liver metastasis. To investigate the safety of the compounds on normal tissues, the percentage mortality was examined. The ethyl iso-allocholate showed zero percent mortality of zebrafish. These results indicate that the steroidal derivative isolated from T. foenum-graecum seeds induces caspase dependent apoptosis in cancer cells and reduces tumor growth, metastasis and angiogenesis in vivo, as well as it is safe on the normal tissues. The in vitro and in vivo anticancer studies suggest that the cytotoxic compound ethyl iso-allocholate has potential application in pharmaceutical industry., (Copyright © 2018. Published by Elsevier Taiwan LLC.)