Centromere sequence-independent but biased loading of subgenome-specific CENH3 variants in allopolyploid Arabidopsis suecica.

Centromeric nucleosomes are determined by the replacement of the canonical histone H3 with the centromere-specific histone H3 (CENH3) variant. Little is known about the centromere organization in allopolyploid species where different subgenome-specific CENH3s and subgenome-specific centromeric sequences coexist. Here, we analyzed the transcription and centromeric localization of subgenome-specific CENH3 variants in the allopolyploid species Arabidopsis suecica. Synthetic A. thaliana x A. arenosa hybrids were generated and analyzed to mimic the early evolution of A. suecica. Our expression analyses indicated that CENH3 has generally higher expression levels in A. arenosa compared to A. thaliana, and this pattern persists in the hybrids. We also demonstrated that despite a different centromere DNA composition, the centromeres of both subgenomes incorporate CENH3 encoded by both subgenomes, but with a positive bias towards the A. arenosa-type CENH3. The intermingled arrangement of both CENH3 variants demonstrates centromere plasticity and may be an evolutionary adaption to handle more than one CENH3 variant in the process of allopolyploidization.

Exponential Shortcut to Measurement-Induced Entanglement Phase Transitions.

Recently discovered measurement-induced entanglement phase transitions in monitored quantum circuits provide a novel example of far-from-equilibrium quantum criticality. Here, we propose a highly efficient strategy for experimentally accessing these transitions through fluctuations. Instead of directly measuring entanglement entropy, which requires an exponential number of measurements in the subsystem size, our method provides a scalable approach to entanglement transitions in the presence of conserved quantities. In analogy to entanglement entropy and mutual information, we illustrate how bipartite and multipartite fluctuations can both be employed to analyze the measurement-induced criticality. Remarkably, the phase transition can be revealed by measuring fluctuations of only a handful of qubits.

HDAC3 Knockdown Dysregulates Juvenile Hormone and Apoptosis-Related Genes in Helicoverpa armigera.

Insect development requires genes to be expressed in strict spatiotemporal order. The dynamic regulation of genes involved in insect development is partly orchestrated by the histone acetylation-deacetylation via histone acetyltransferases (HATs) and histone deacetylases (HDACs). Although histone deacetylase 3 (HDAC3) is required for mice during early embryonic development, its functions in Helicoverpa armigera (H. armigera) and its potential to be used as a target of insecticides remain unclear. We treated H. armigera with HDAC3 siRNA and RGFP966, a specific inhibitor, examining how the HDAC3 loss-of-function affects growth and development. HDAC3 siRNA and RGFP966 treatment increased mortality at each growth stage and altered metamorphosis, hampering pupation and causing abnormal wing development, reduced egg production, and reduced hatching rate. We believe that the misregulation of key hormone-related genes leads to abnormal pupa development in HDAC3 knockout insects. RNA-seq analysis identified 2788 differentially expressed genes (≥two-fold change; p ≤ 0.05) between siHDAC3- and siNC-treated larvae. Krüppel homolog 1 (Kr-h1), was differentially expressed in HDAC3 knockdown larvae. Pathway-enrichment analysis revealed the significant enrichment of genes involved in the Hippo, MAPK, and Wnt signaling pathways following HDAC3 knockdown. Histone H3K9 acetylation was increased in H. armigera after siHDAC3 treatment. In conclusion, HDAC3 knockdown dysregulated juvenile hormone (JH)-related and apoptosis-related genes in H. armigera. The results showed that the HDAC3 gene is a potential target for fighting H. armigera.

Challenges to manage pandemic of coronavirus disease (COVID-19) in Iran with a special situation: a qualitative multi-method study.

BACKGROUND: With the unprecedented expansion of COVID-19 in the world since December 2019, Iran's health system, like other countries, faced various challenges in managing the disease, which led to numerous experiences and lessons learned. This study was conducted to identify these challenges regarding unique political, economic, and cultural issues, which could help other countries with similar situations. METHODS: The present study was performed using a qualitative multi-method approach with a content analysis method. The data were collected through in-depth and semi-structured interviews and focused group discussions with 60 key persons who were selected purposefully, including policymakers, health care workers, and affected people by the disease, and the review of all available national reports between February 21, 2020, and March 22, 2021. The data collection and analysis were done simultaneously. RESULTS: Identified critical challenges for the management of COVID-19 in the health system were limited evidence and scientific controversies, poor social prevention and social inequalities, burnout and sustained workload among healthcare workers, improper management of resources and equipment, the lack of a guideline for contact tracing, and patient flow management, and mental health problems in the community. CONCLUSIONS: According to our results, measures should be taken to conduct a continuous comprehensive risk assessment and develop a national response plan with an emphasis on precise contact tracing, active screening, patient flow, paying attention to the psychological and social dimensions of the disease, and also transparency of social inequalities in the face of risk factors of the COVID-19. Also, the social protection programs should become a vital tool for policymakers and supporting the vulnerable groups using the capacity of the community and international cooperation to develop a vaccine, which is difficult to procure due to the sanctions.

Highly Tunable Spin-Orbit Torque and Anisotropic Magnetoresistance in a Topological Insulator Thin Film Attached to Ferromagnetic Layer.

We investigate spin-charge conversion phenomena in hybrid structures of topological insulator thin films and magnetic insulators. We find an anisotropic inverse spin-galvanic effect that yields a highly tunable spin-orbit torque. Concentrating on the quasiballistic limit, we also predict a giant anisotropic magnetoresistance at low dopings. These effects, which have no counterparts in thick topological insulators, depend on the simultaneous presence of the hybridization between the surface states and the in-plane magnetization. Both the inverse spin-galvanic effect and anisotropic magnetoresistance exhibit a strong dependence on the magnetization and the Fermi level position and can be used for spintronics and spin-orbit-torque-based applications at the nanoscale.

Helicobacter pylori infection as a risk factor for diabetes: a meta-analysis of case-control studies.

BACKGROUND: There are several studies with varied and mixed results about the possible relationship between H. pylori and diabetes. Therefore, this current meta-analysis performed to determine the association between H. pylori infection and the risk of diabetes mellitus. METHODS: A systematic literature searches of international databases, including Medline (PubMed), Web of Sciences, Scopus, EMBASE, and CINHAL (January 1990-March 2019) was conducted to identify studies investigating the relationship between H. pylori infection and diabetes mellitus. Only case-control studies were analyzed using odds ratio (OR) with 95% confidence intervals (CIs). Stratified and subgroup analyses were performed to explore heterogeneity between studies and assess effects of study quality. Logarithm and standard error logarithm odds ratio (OR) were also used for meta-analysis. RESULTS: A total of 41 studies involving 9559 individuals (case; 4327 and control; 5232) were analyzed. The pooled estimate of the association between H. pylori infection with diabetes was OR = 1.27 (95% CI 1.11 to 1.45, P = 0.0001, I2 = 86.6%). The effect of H. pylori infection on diabetes mellitus (both types), type 1 and type 2 diabetes was 1.17 (95% CI 0.94 to 1.45), 1.19 (95% CI 0.98 to 1.45), and 1.43 (95% CI 1.11 to 1.85) respectively. Subgroup analysis by the geographical regions showed in Asian population risk of the effect of H. pylori infection on diabetes was slightly higher than other population, CONCLUSION: In overall a positive association between H. pylori infection and diabetes mellitus was found.

Religion, Spirituality and Risk of Coronary Heart Disease: A Matched Case-Control Study and Meta-Analysis.

Although the association between religion/spirituality (R/S) and psychological outcomes is well established, current understanding of the association with cardiovascular disease remains limited. We sought to investigate the association between Islamic R/S and coronary heart disease (CHD), and place these findings in light of a meta-analysis. In this case-control study, 190 cases with non-fatal CHD were identified and individually matched with 383 hospital-based controls. R/S was measured by self-administered 102 items questionnaire. A tabular meta-analysis was performed of observational studies on R/S (high level versus low level) and CHD. In addition, a dose-response meta-analysis was conducted using generalized least-squares regression. Participants in the top quartile had decreased odds of CHD comparing to participants in the lowest quartile of religious belief (OR 0.20, 95% confidence interval (CI) 0.06-0.59), religious commitment (OR 0.36, CI 95% 0.13-0.99), religious emotions (OR 0.39, CI 95% 0.18-0.87), and total R/S score (OR 0.30, CI 95% 0.13-0.67). The meta-analysis study showed a significant relative risk of 0.88 (CI 95% 0.77-1.00) comparing individuals in high level versus low level of R/S. In dose-response meta-analysis, comparing people with no religious services attendance, the relative risks of CHD were 0.77 (CI 95% 0.65-0.91) for one times attendance and 0.27 (CI 95% 0.11-0.65) for five times attendance per month. R/S was associated with a significantly decreased risk of CHD. The possible causal nature of the observed associations warrants randomized clinical trial with large sample size.

hOGG1 gene polymorphism and breast cancer risk: A systematic review and meta-analysis study.

To address the effect of hGGO1 (rs1052133) gene polymorphism on the risk of breast cancer, a meta-analysis was performed. We pooled adjusted odds ratios (OR) as overall and three subgroups (menopausal status, ethnicity, and study setting). In overall analysis, we found a significant association when the model of inheritance was homozygote (pooled OR 1.14; 95% CI 1.01, 1.29). Subgroup analysis showed significant association for homozygote genetic models among postmenopause women (OR 1.23; 95% CI 1.01, 1.49) and Asian population (OR 1.17; 95% CI 1.01, 1.35). This study suggested that the carrier of Ser326Cys polymorphism of hOGG1, Cys/Cys vs Ser/Ser, are at higher risk for breast cancer, independent of other hormonal and environmental risk factors.

Point mutation impairs centromeric CENH3 loading and induces haploid plants.

The chromosomal position of the centromere-specific histone H3 variant CENH3 (also called "CENP-A") is the assembly site for the kinetochore complex of active centromeres. Any error in transcription, translation, modification, or incorporation can affect the ability to assemble intact CENH3 chromatin and can cause centromere inactivation [Allshire RC, Karpen GH (2008) Nat Rev Genet 9 (12):923-937]. Here we show that a single-point amino acid exchange in the centromere-targeting domain of CENH3 leads to reduced centromere loading of CENH3 in barley, sugar beet, and Arabidopsis thaliana. Haploids were obtained after cenh3 L130F-complemented cenh3-null mutant plants were crossed with wild-type A. thaliana. In contrast, in a noncompeting situation (i.e., centromeres possessing only mutated or only wild-type CENH3), no uniparental chromosome elimination occurs during early embryogenesis. The high degree of evolutionary conservation of the identified mutation site offers promising opportunities for application in a wide range of crop species in which haploid technology is of interest.

Understanding Female Students' Needs to Develop Health Promoting School Programme: An Exploratory Qualitative Analysis.

BACKGROUND: This study was carried out on Iranian female adolescents to understand health needs for the purpose of designing health promoting intervention in schools. METHODS: In this exploratory qualitative study, two focus group discussion (15 teachers) and 30 individual in-depth interviews were conducted among female adolescents in the eighth grade in Zahedan, Iran. Qualitative content analysis was used for data evaluation. RESULTS: The views of students and teachers demonstrated nine of needs including: informing students about the schools' health project aims, education and training all dimensions of health with an emphasis on mental health, use of experts in various fields for education from other organisations, employing capable and trusted counselors in schools, utilisation of a variety of teaching methods, activating reward systems for encouraging students' participation in group activities, teaching communication and the ability to establish good relationships with parents and strategies for resolving family conflict, teaching parents and students high-risk behaviours and strategies for handling them as well as reforming wrong attitudes and indigenous sub-culture. CONCLUSION: This study found the different needs of Iranian female students compared to other cultures about a health promoting school programme. Therefore, their contribution can provide an insight for formulating policies and intervention in schools.

Cancerouspdomains: comprehensive analysis of cancer type-specific recurrent somatic mutations in proteins and domains.

BACKGROUND: Discriminating driver mutations from the ones that play no role in cancer is a severe bottleneck in elucidating molecular mechanisms underlying cancer development. Since protein domains are representatives of functional regions within proteins, mutations on them may disturb the protein functionality. Therefore, studying mutations at domain level may point researchers to more accurate assessment of the functional impact of the mutations. RESULTS: This article presents a comprehensive study to map mutations from 29 cancer types to both sequence- and structure-based domains. Statistical analysis was performed to identify candidate domains in which mutations occur with high statistical significance. For each cancer type, the corresponding type-specific domains were distinguished among all candidate domains. Subsequently, cancer type-specific domains facilitated the identification of specific proteins for each cancer type. Besides, performing interactome analysis on specific proteins of each cancer type showed high levels of interconnectivity among them, which implies their functional relationship. To evaluate the role of mitochondrial genes, stem cell-specific genes and DNA repair genes in cancer development, their mutation frequency was determined via further analysis. CONCLUSIONS: This study has provided researchers with a publicly available data repository for studying both CATH and Pfam domain regions on protein-coding genes. Moreover, the associations between different groups of genes/domains and various cancer types have been clarified. The work is available at http://www.cancerouspdomains.ir .

Rye B chromosomes encode a functional Argonaute-like protein with in vitro slicer activities similar to its A chromosome paralog.

B chromosomes (Bs) are supernumerary, dispensable parts of the nuclear genome, which appear in many different species of eukaryote. So far, Bs have been considered to be genetically inert elements without any functional genes. Our comparative transcriptome analysis and the detection of active RNA polymerase II (RNAPII) in the proximity of B chromatin demonstrate that the Bs of rye (Secale cereale) contribute to the transcriptome. In total, 1954 and 1218 B-derived transcripts with an open reading frame were expressed in generative and vegetative tissues, respectively. In addition to B-derived transposable element transcripts, a high percentage of short transcripts without detectable similarity to known proteins and gene fragments from A chromosomes (As) were found, suggesting an ongoing gene erosion process. In vitro analysis of the A- and B-encoded AGO4B protein variants demonstrated that both possess RNA slicer activity. These data demonstrate unambiguously the presence of a functional AGO4B gene on Bs and that these Bs carry both functional protein coding genes and pseudogene copies. Thus, B-encoded genes may provide an additional level of gene control and complexity in combination with their related A-located genes. Hence, physiological effects, associated with the presence of Bs, may partly be explained by the activity of B-located (pseudo)genes.

Genes on B chromosomes: old questions revisited with new tools.

BACKGROUND: B chromosomes are supernumerary dispensable parts of the karyotype which appear in some individuals of some populations in some species. Often, they have been considered as 'junk DNA' or genomic parasites without functional genes. SCOPE OF REVIEW: Due to recent advances in sequencing technologies, it became possible to investigate their DNA composition, transcriptional activity and effects on the host transcriptome profile in detail. Here, we review the most recent findings regarding the gene content of B chromosomes and their transcriptional activities and discuss these findings in the context of comparable biological phenomena, like sex chromosomes, aneuploidy and pseudogenes. MAJOR CONCLUSIONS: Recent data suggest that B chromosomes carry transcriptionally active genic sequences which could affect the transcriptome profile of their host genome. GENERAL SIGNIFICANCE: These findings are gradually changing our view that B chromosomes are solely genetically inert selfish elements without any functional genes. This at one side could partly explain the deleterious effects which are associated with their presence. On the other hand it makes B chromosome a nice model for studying regulatory mechanisms of duplicated genes and their evolutionary consequences.

Introduction of high nitrogen doped graphene as a new cationic carrier in electromembrane extraction.

This paper proposes for the first time, the use of high nitrogen doped graphene (HND-G) as a new cationic carrier for the enhancement of electromembrane extraction (EME) performance. Sensitivity of EME was improved by the modification of supported liquid membrane composition through the addition of HND-G into 1-octanol for the extraction of naproxen and sodium diclofenac as model acidic drugs. The comparison between HND-G-modified EME and conventional EME showed that HND-G could increase the overall partition coefficient of acidic drugs in the membrane due to the fact that HND-G acts as an ion pair reagent and there is an electrostatic interaction between positively charged HND-G and acidic drugs with negative charge. During the extraction, model acidic drugs migrated from a 10 mL aqueous sample solution (pH 9.6) through a thin layer of 1-octanol containing 0.6% w/v of HND-G that was impregnated in the pores of a hollow fiber, into a 30 µL basic aqueous acceptor solution (pH 12.3) present in the lumen of the hollow fiber. Equilibrium extraction conditions were obtained after 16 min of operation with the whole assembly agitated at 1000 rpm. Under the optimized conditions, the enrichment factors were between 238 and 322 and also the LODs ranged from 0.1 to 0.7 ng/mL in different samples. Finally, the applicability of this method was evaluated by the extraction and determination of drugs of interest in real urine samples.

Formation and expression of pseudogenes on the B chromosome of rye.

B chromosomes (Bs) are dispensable components of the genomes of numerous species. In contrast with the prevalent view that Bs do not harbor genes, our recent sequence analysis revealed that Bs of rye (Secale cereale) are rich in gene-derived sequences. We compared these gene-like fragments of the rye B with their ancestral A-located counterparts and confirmed an A chromosomal origin and the pseudogenization of B-located gene-like fragments. About 15% of the pseudogene-like fragments on Bs are transcribed in a tissue-type and genotype-specific manner. In addition, B-located sequences can cause in trans down- or upregulation of A chromosome-encoded genic fragments. Phenotypes and effects associated with the presence of Bs might be explained by the activity of B-located pseudogenes. We propose a model for the evolution of B-located pseudogenes.

The differential loading of two barley CENH3 variants into distinct centromeric substructures is cell type- and development-specific.

The organization of centromeric chromatin of diploid barley (Hordeum vulgare) encoding two (α and ß) CENH3 variants was analysed by super-resolution microscopy. Antibody staining revealed that both CENH3 variants are organized in distinct but intermingled subdomains in interphase, mitotic and meiotic centromeres. Artificially extended chromatin fibres illustrate that these subdomains are formed by polynucleosome clusters. Thus, a CENH3 variant-specific loading followed by the arrangement into specific intermingling subdomains forming the centromere region appears. The CENH3 composition and transcription vary among different tissues. In young embryos, most interphase centromeres are composed of both CENH3 variants, while in meristematic root cells, a high number of nuclei contain ßCENH3 mainly dispersed within the nucleoplasm. A similar distribution and no preferential arrangement of the two CENH3 variants in relationship to the spindle poles suggest that both homologs meet the same function in metaphase cells.

Sensitivity to nitazoxanide among metronidazole resistant Helicobacter pylori strains in patients with gastritis.

BACKGROUND: In this study, the efficacy of nitazoxanide in the treatment of Helicobacter pylori isolates, which were resistant to metronidazole, was examined. METHODS: One hundred twenty two patients who underwent endoscopy examinations at Kasra and Laleh hospitals in Tehran from November 2014 to July 2015 were enrolled. Helicobacter pylori strains were isolated from the patients' endoscopy biopsies by bacteriological culture. Those bacterial isolates resistant to metronidazole were examined for susceptibility to nitazoxanide. Serial agar dilution method was utilized to determine the minimum inhibitory concentrations for the antibiotics. RESULTS: From 122 gastric biopsy specimens, 55 H. pylori isolates were recovered (45%); of which, 40 (72.7%) were resistant to metronidazole. Comparing the MIC values of nitazoxanide with metronidazole revealed significant differences (p<0.05). The MIC50 and MIC90 values for nitazoxanide and metronidazole were 8 and ≥8µg/ml, and 32 and 64µg/ml, respectively. CONCLUSION: The high levels of metronidazole resistance suggest that this medication may not be beneficial for first-line therapy in Iran. However, considering the relative effectiveness of nitazoxanide, it may be considered a suitable alternative for patients in Iran.

Nondisjunction in favor of a chromosome: the mechanism of rye B chromosome drive during pollen mitosis.

B chromosomes (Bs) are supernumerary components of the genome and do not confer any advantages on the organisms that harbor them. The maintenance of Bs in natural populations is possible by their transmission at higher than Mendelian frequencies. Although drive is the key for understanding B chromosomes, the mechanism is largely unknown. We provide direct insights into the cellular mechanism of B chromosome drive in the male gametophyte of rye (Secale cereale). We found that nondisjunction of Bs is accompanied by centromere activity and is likely caused by extended cohesion of the B sister chromatids. The B centromere originated from an A centromere, which accumulated B-specific repeats and rearrangements. Because of unequal spindle formation at the first pollen mitosis, nondisjoined B chromatids preferentially become located toward the generative pole. The failure to resolve pericentromeric cohesion is under the control of the B-specific nondisjunction control region. Hence, a combination of nondisjunction and unequal spindle formation at first pollen mitosis results in the accumulation of Bs in the generative nucleus and therefore ensures their transmission at a higher than expected rate to the next generation.

Evolution and biology of supernumerary B chromosomes.

B chromosomes (Bs) are dispensable components of the genome exhibiting non-Mendelian inheritance and have been widely reported on over several thousand eukaryotes, but still remain an evolutionary mystery ever since their first discovery over a century ago [1]. Recent advances in genome analysis have significantly improved our knowledge on the origin and composition of Bs in the last few years. In contrast to the prevalent view that Bs do not harbor genes, recent analysis revealed that Bs of sequenced species are rich in gene-derived sequences. We summarize the latest findings on supernumerary chromosomes with a special focus on the origin, DNA composition, and the non-Mendelian accumulation mechanism of Bs.

Selfish supernumerary chromosome reveals its origin as a mosaic of host genome and organellar sequences.

Supernumerary B chromosomes are optional additions to the basic set of A chromosomes, and occur in all eukaryotic groups. They differ from the basic complement in morphology, pairing behavior, and inheritance and are not required for normal growth and development. The current view is that B chromosomes are parasitic elements comparable to selfish DNA, like transposons. In contrast to transposons, they are autonomously inherited independent of the host genome and have their own mechanisms of mitotic or meiotic drive. Although B chromosomes were first described a century ago, little is known about their origin and molecular makeup. The widely accepted view is that they are derived from fragments of A chromosomes and/or generated in response to interspecific hybridization. Through next-generation sequencing of sorted A and B chromosomes, we show that B chromosomes of rye are rich in gene-derived sequences, allowing us to trace their origin to fragments of A chromosomes, with the largest parts corresponding to rye chromosomes 3R and 7R. Compared with A chromosomes, B chromosomes were also found to accumulate large amounts of specific repeats and insertions of organellar DNA. The origin of rye B chromosomes occurred an estimated ∼1.1-1.3 Mya, overlapping in time with the onset of the genus Secale (1.7 Mya). We propose a comprehensive model of B chromosome evolution, including its origin by recombination of several A chromosomes followed by capturing of additional A-derived and organellar sequences and amplification of B-specific repeats.