BRCA2 Polymorphisms and Breast Cancer Susceptibility: a Multi-Tools Bioinformatics Approach.

BACKGROUND/AIMS: The main focus of this investigation is to identify deleterious single nucleotide polymorphisms (SNPs) located in the BRCA2 gene through in silico approach, thereby,providing an understanding of potential consequences regarding the susceptibility to breast cancer. METHODS: The GenomAD database was used to identify SNPs. To determine the potential adverse consequences, our study employed various prediction tools, including SIFT, PolyPhen, PredictSNP, SNAP2, PhD-SNP, and ClinVar. The pathogenicity associated with the deleterious snSNPs was evaluated bu MutPred and Fathmm. Additionally, I-Mutant and MuPro were used to assess the stability, followed by conservation and protein-protein interaction analysis using robust computational tools. The 3D structure of BRCA2 protein was generated by SwissModel, followed by validation using PROCHECK and Errat. RESULTS: The GenomAD database was used to identify a total of 7, 921 SNPs, including 1940 missense SNPs. A set of 69 SNPs predicted by consensus to be damaging across all platforms was identified. Mutpred and Fathmm identified 48 and 38 SNPs, respectively to be associated with cancer. While I- Mutant and MuPro assays suggested 22 SNPs to decrease protein stability. Additionally, these 22 SNPs reside within highly conserved regions of the BRCA2 protein. Domain analysis, utilizing InterPro, pinpointed 18 deleterious mutations within crucial DNA binding domains and one in the BRC repeat region. CONCLUSION: This study establishes a foundation for future experimental validations and the creation of breast cancer-targeted treatment approaches.

Significant Association of Candidate Genes (AGTR1 and TGF-Β1) Polymorphism with Diabetic Nephropathy in Diabetes Mellitus Type 2 Patients.

BACKGROUND/AIMS: Diabetic nephropathy (DN) is one of the complications of diabetes mellitus (DM). This study aimed to investigate the association between genetic polymorphisms, specifically AGTR1 (rs5186) and TGF-ß1 (rs1800470), and the risk of developing Diabetic nephropathy (DN) in type 2 diabetes mellitus patients, compared to those without DN and healthy controls. METHODS: A case-control study was conducted on 165 diabetic patients (59 with diabetic nephropathy (DN) and 54 without DN (DM)), and 52 healthy controls (HC). The genotyping was done using amplification refractory mutation system method (ARMS-PCR). Age, gender, and duration of diabetes were matched across groups. Clinical parameters including FBS, RBS, HbA1C, creatinine, urea, SBP, DBP, total cholesterol, triglycerides, LDL, and BMI were assessed. RESULTS: Diabetic patients with nephropathy exhibited significantly higher levels of clinical parameters compared to those without nephropathy and healthy controls. The risk allele of AGTR1 , C (p <0.0001), and risk allele containing genotypes AC (p <0.0001) and CC (p - 0.0010) were significantly higher in DN patients compared to DM and HC groups. Similarly, the TGF-ß1 risk allele C (p - 0.0001), and corresponding genotypes TC (p - 0.0038) and CC (p - 0.0027) were significantly associated with increased risk of diabetic nephropathy compared to DM and HC groups. CONCLUSION: The data showed significant association of AGTR1 (rs5186) and TGF-ß1 (rs1800470) polymorphism with an increased risk of diabetic nephropathy in type 2 diabetes mellitus patients. More investigation will be required to disseminate the results, while increasing the samples size and using whole genome sequencing.

Transcriptome analysis and identification of the low potassium stress-responsive gene SiSnRK2.6 in foxtail millet (Setaria italica L.).

KEY MESSAGE: The transcriptome is beneficial for dissecting the mechanism of millet in response to low potassium stress and SiSnRK2.6 was identified as a potential target for improving low potassium stress tolerance. Foxtail millet (Setaria italica L.), which originated in China, has high nutrient utilization character. Nevertheless, the molecular mechanism of its tolerance to low potassium stress is largely unclear. In this research, the low potassium tolerant variety "Yugu28" was screened out by low potassium stress treatment, and the transcriptome of "Yugu28" under low potassium stress was comprehensively analyzed. A total of 4254 differentially expressed genes (DEGs) were identified, including 1618 up-regulated and 2636 down-regulated genes, respectively. In addition, there were 302 transcription factor (TF) genes in the DEGs and MYB TFs accounted for the highest proportion, which was 14.9%. After functional analysis of all DEGs, a total of 7 genes involved in potassium transport and potassium ion channels and 50 genes corresponding to hormones were screened. The expression levels of randomly selected 17 DEGs were verified by qRT-PCR and the results coincided well with the RNA-seq analysis, indicating the reliability of our transcriptome data. Moreover, one of the ABA signaling pathway genes, SiSnRK2.6, was identified and selected for further functional verification. Compared with the wild type, transgenic rice with ecotopic expression of SiSnRK2.6 showed remarkably increased root length and root number, indicating that overexpression of SiSnRK2.6 can enhance the resistance of transgenic plants to low potassium stress.

QTL detection and candidate gene identification of qCTB1 for cold tolerance in the Yunnan plateau landrace rice.

Cold stress is one of the main abiotic stresses that affects rice growth and production worldwide. Dissection of the genetic basis is important for genetic improvement of cold tolerance in rice. In this study, a new source of cold-tolerant accession from the Yunnan plateau, Lijiangxiaoheigu, was used as the donor parent and crossed with a cold-sensitive cultivar, Deyou17, to develop recombinant inbred lines (RILs) for quantitative trait locus (QTL) analysis for cold tolerance at the early seedling and booting stages in rice. In total, three QTLs for cold tolerance at the early seedling stage on chromosomes 2 and 7, and four QTLs at the booting stage on chromosomes 1, 3, 5, and 7, were identified. Haplotype and linear regression analyses showed that QTL pyramiding based on the additive effect of these favorable loci has good potential for cold tolerance breeding. Effect assessment in the RIL and BC3F3 populations demonstrated that qCTB1 had a stable effect on cold tolerance at the booting stage in the genetic segregation populations. Under different cold stress conditions, qCTB1 was fine-mapped to a 341-kb interval between markers M3 and M4. Through the combination of parental sequence comparison, candidate gene-based association analysis, and tissue and cold-induced expression analyses, eight important candidate genes for qCTB1 were identified. This study will provide genetic resources for molecular breeding and gene cloning to improve cold tolerance in rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01488-3.

BRAF and RET polymorphism association with thyroid cancer risk, a preliminary study from Khyber Pakhtunkhwa population.

BACKGROUND: Thyroid cancer, originating in the neck's thyroid gland, encompasses various types. Genetic mutations, particularly in BRAF and RET genes are crucial in its development. This study investigates the association between BRAF (rs113488022) and RET (rs77709286) polymorphisms and thyroid cancer risk in the Khyber Pakhtunkhwa (KP) population. METHODS: Blood samples from 100 thyroid cancer patients and 100 healthy controls were genotyped using ARMS-PCR followed by gel electrophoresis and statistical analysis. RESULTS: Analysis revealed a significant association between the minor allele T of BRAF (rs113488022) and thyroid cancer risk (P = 0.0001). Both genotypes of BRAF (rs113488022) showed significant associations with thyroid cancer risk (AT; P = 0.0012 and TT; P = 0.045). Conversely, the minor allele G of RET (rs77709286) exhibited a non-significant association with thyroid cancer risk (P = 0.2614), and neither genotype showed significant associations (CG; P = 0.317, GG; P = 0.651). Demographic and clinical parameters analysis using SPSS showed a non-significant association between BRAF and RET variants and age group (P = 0.878 and P = 0.536), gender (P = 0.587 and P = 0.21), tumor size (P = 0.796 and P = 0.765), or tumor localization (P = 0.689 and P = 0.727). CONCLUSION: In conclusion, this study emphasizes the significant association between BRAF polymorphism and thyroid cancer risk, while RET polymorphism showed a less pronounced impact. Further validation using larger and specific datasets is essential to establish conclusive results.

Association analysis of miRNA-146a and miRNA-196a polymorphism with breast cancer risk in Khyber Pakhtunkhwa, Pakistan: a preliminary study.

BACKGROUND: microRNAs (miRNAs) are small, noncoding RNA molecules, functioning either as oncogenes or tumor suppressor genes. SNPs in miRNAs might modify the expression of genes associated with miRNAs, enhancing susceptibility to breast cancer. Both miRNA-146a (rs2910164) and miRNA-196a (rs11614913) are identified and significantly associated with breast cancer risk in several ethnicities, but remains unexplored in Khyber Pakhtunkhwa population of Pakistan. METHODS: This study was aimed to check the relation of selected SNPs with breast cancer risk. The research cohort included 100 breast cancer patients and 100 healthy controls. All the participants were subjected for DNA extraction followed by T-ARMS PCR and gel electrophoresis. RESULTS: The results revealed a strong association between risk allele (G) of miRNA-146a and increased risk of breast cancer (OR = 2.04, P = 0.0006). Similarly, heterozygous and mutant genotypes also indicated high risk and significant association with breast cancer risk (CG; OR = 0.51, 9 P = 0.0001) (GG; OR = 3.76, P = 0.04). However, risk allele (T) of miRNA-196a (rs11614913) failed to exhibit significant association with breast cancer risk (OR = 0.92 P = 0.68). Similarly, the heterozygous and mutant genotype did not show significant association with breast cancer risk (CT; OR = 0.52, P = 0.125 (TT; OR = 0.88, P = 0.84). Furthermore, miRNA-146a (rs2910164) and miRNA-196a (rs11614913) polymorphisms exhibited non-significant associations with family history (P = 0.34, P = 0.77), PR status (P = 0.310, P = 0.397), ER status (P = 0.992, P = 0.981), nodal status (P = 0.86, P = 0.90), and menstrual status (P = 0.97, P = 0.09). Notably, miRNA-196a showed a significant association with the metastasis group (P = 0.010) and cancer stages (P = 0.047). CONCLUSIONS: In conclusion, this study highlights the association of miRNA-146a (rs2910164) polymorphism with breast cancer risk but suggested non-significant association of miRNA-196a (rs11614913) with breast cancer risk. However, these findings need to be confirmed through larger data set for more accurate result.

Natural variation in MORE GRAINS 1 regulates grain number and grain weight in rice.

Grain yield is determined mainly by grain number and grain weight. In this study, we identified and characterized MORE GRAINS1 (MOG1), a gene associated with grain number and grain weight in rice (Oryza sativa L.), through map-based cloning. Overexpression of MOG1 increased grain yield by 18.6%-22.3% under field conditions. We determined that MOG1, a bHLH transcription factor, interacts with OsbHLH107 and directly activates the expression of LONELY GUY (LOG), which encodes a cytokinin-activating enzyme and the cell expansion gene EXPANSIN-LIKE1 (EXPLA1), positively regulating grain number per panicle and grain weight. Natural variations in the promoter and coding regions of MOG1 between Hap-LNW and Hap-HNW alleles resulted in changes in MOG1 expression level and transcriptional activation, leading to functional differences. Haplotype analysis revealed that Hap-HNW, which results in a greater number and heavier grains, has undergone strong selection but has been poorly utilized in modern lowland rice breeding. In summary, the MOG1-OsbHLH107 complex activates LOG and EXPLA1 expression to promote cell expansion and division of young panicles through the cytokinin pathway, thereby increasing grain number and grain weight. These findings suggest that Hap-HNW could be used in strategies to breed high-yielding temperate japonica lowland rice.

Cold-adaptive evolution at the reproductive stage in Geng/japonica subspecies reveals the role of OsMAPK3 and OsLEA9.

Cold stress at the reproductive stage severely affects the production and geographic distribution of rice. The Geng/japonica subpopulation gradually developed stronger cold adaptation than the Xian/indica subpopulation during the long-term domestication of cultivated rice. However, the evolutionary path and natural alleles underlying the cold adaptability of intra-Geng subspecies remain largely unknown. Here, we identified MITOGEN-ACTIVATED PROTEIN KINASE 3 (OsMAPK3) and LATE EMBRYOGENESIS ABUNDANT PROTEIN 9 (OsLEA9) as two important regulators for the cold adaptation of Geng subspecies from a combination of transcriptome analysis and genome-wide association study. Transgenic validation showed that OsMAPK3 and OsLEA9 confer cold tolerance at the reproductive stage. Selection and evolution analysis suggested that the Geng version of OsMAPK3 (OsMAPK3Geng ) directly evolved from Chinese Oryza rufipogon III and was largely retained in high-latitude and high-altitude regions with low temperatures during domestication. Later, the functional nucleotide polymorphism (FNP-776) in the Kunmingxiaobaigu and Lijiangxiaoheigu version of the OsLEA9 (OsLEA9KL ) promoter originated from novel variation of intra-Geng was selected and predominantly retained in temperate Geng to improve the adaptation of Geng together with OsMAPK3Geng to colder climatic conditions in high-latitude areas. Breeding potential analysis suggested that pyramiding of OsMAPK3Geng and OsLEA9KL enhanced the cold tolerance of Geng and promotes the expansion of cultivated rice to colder regions. This study not only highlights the evolutionary path taken by the cold-adaptive differentiation of intra-Geng, but also provides new genetic resources for rice molecular breeding in low-temperature areas.

Natural variation in Tiller Number 1 affects its interaction with TIF1 to regulate tillering in rice.

Tiller number per plant-a cardinal component of ideal plant architecture-affects grain yield potential. Thus, alleles positively affecting tillering must be mined to promote genetic improvement. Here, we report a Tiller Number 1 (TN1) protein harbouring a bromo-adjacent homology domain and RNA recognition motifs, identified through genome-wide association study of tiller numbers. Natural variation in TN1 affects its interaction with TIF1 (TN1 interaction factor 1) to affect DWARF14 expression and negatively regulate tiller number in rice. Further analysis of variations in TN1 among indica genotypes according to geographical distribution revealed that low-tillering varieties with TN1-hapL are concentrated in Southeast Asia and East Asia, whereas high-tillering varieties with TN1-hapH are concentrated in South Asia. Taken together, these results indicate that TN1 is a tillering regulatory factor whose alleles present apparent preferential utilization across geographical regions. Our findings advance the molecular understanding of tiller development.

Association of candidate genes (ALR2, RAGE, and VEGF) polymorphisms with diabetic retinopathy in type 2 diabetic patients of Khyber Pakhtunkhwa, Pakistan.

AIM: To evaluate the aldose reductase (ALR2, rs759853), receptor for advanced glycation end products (RAGE, rs2070600), and vascular endothelial growth factor (VEGF, rs833061) association with diabetic retinopathy in type 2 diabetic patients of Khyber Pakhtunkhwa population. METHODS: A case-control study was conducted on a total of 550 subjects consisting of 186 with diabetic retinopathy (DR) having type 2 diabetes, 180 had type 2 diabetes (T2DM), and 184 healthy controls (HC). All the samples were subjected to DNA isolation using salting-out method followed by SNP genotyping through Tetra-ARMS PCR. Chi square and Exact Fischer tests were used for alleles and genotypes distribution. Odd ratio and confidence interval values were found out by online software Medcalc Odd ratio Calculator. RESULTS: Multiple parameters such as random blood sugar (RBS) (p < 0.001), fasting blood sugar (FBS) (p < 0.001), HbA1c (p < 0.001), total cholesterol (p < 0.001), LDL (p < 0.001), HDL (p < 0.001), BMI (p < 0.001) and hypertension (p = 0.018) exhibited strong association with DR as compared to DM and HC. Our results displayed that the VEGF-rs833061 and RAGE- rs2070600 exhibited significant association (p < 0.05) with an increased DR risk, when compared with T2DM. In contrast, ALR2 didn't display association with DR (p > 0.05) when compared with T2DM, but showed association (p < 0.05) when compared with HC. CONCLUSION: Statistically significant association was observed in VEGF-rs833061 and RAGE-rs2070600 with DR in type 2 diabetic patients. While, ALR2- rs759853 didn't exhibit significant association with DR. This is the first study to report the association of candidate genes (ALR2, VEGF and RAGE) with DR in type 2 diabetes of Khyber Pakhtunkhwa population. More similar research studies are recommended with larger data sets in other ethnicities both national and international.

Estrogen receptor alpha (ESR1) gene polymorphism (rs2234693 and rs2046210) with breast cancer risk in pashtun population of Khyber Pakhtunkhwa.

BACKGROUND: Breast cancer susceptibility is greatly influenced by single nucleotide polymorphisms (SNPs) both in penetrance and non-penetrance genes. The Estrogen Receptor Alfa (ESR1- rs2234693 and rs2046210) have been reported as risk factor of breast cancer in different ethnic groups with inconsistent results. In this study the association of ESR1 (rs2234693 and rs2046210) with breast cancer risk was investigated in patients of Khyber Pakhtunkhwa. METHODS: A total of 312 females including 162 breast cancer patients and 150 healthy controls were enrolled in this study. The polymorphism was confirmed using T-ARMS-PCR. RESULTS: Our results revealed that ESR1-rs2234693 risk allele (C) (P = 0.21, OR = 1.27, CI = 0.87 to 1.87) and containing genotypes CC (P = 0.68, OR = 1.24, CI = 0.42 to 3.68) and TC (P = 0.23, OR = 1.32, CI = 0.83 to 2.13) were not associated with the risk of breast cancer. In case of rs2046210, the risk allele A (P < 0.0001, OR = 2.42, CI = 1.74 to 3.38) and corresponding genotypes GA (P = 0.0001, OR = 2.55, CI = 1.62 to 4.03) and AA (P = 0.02, OR = 2.20, CI = 1.12 to 4.34) were significantly associated with higher risk of breast cancer. Moreover, ESR1-rs2234693 was significantly (P < 0.05) associated with family history, stages, PR status, ER status and luminal B. The ESR1-rs2046210 showed significant (P ≤ 0.05) association with menstrual status, tumor grade and TNBC. Both the SNPs showed non-significant (P > 0.05) association with nulliparity, nodal status, HER2 status, metastasis, HER2 enriched subtype and luminal A. CONCLUSION: It is concluded that ESR1-rs2234693 is not associated with breast cancer, while rs2046210 is significantly associated with the risk of breast cancer in Khyber Pakhtunkhwa population. Further, to confirm the exact situation of ESR1 polymorphism, ESR1 existing and other SNPs need to be investigated in diverse data sets.

Significant association of BRCA1 (rs1799950), BRCA2 (rs144848) and TP53 (rs1042522) polymorphism with breast cancer risk in Pashtun population of Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: Single nucleotide polymorphism (SNPs) in BRCA1, BRCA2 and TP53 has been widely associated with breast cancer risk in different ethnicities with inconsistent results. There is no such study conducted so far in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. Therefore, this study was conducted to check BRCA1 (rs1799950), BRCA2 (rs144848) and TP53 (rs1042522) polymorphism with breast cancer risk in Pashtun population of Khyber Pakhtunkhwa, Pakistan. METHODS: This study, consisting 140 breast cancer patients and 80 gender and age matched healthy controls were subjected to confirm BRCA1, BRCA2 and TP53 polymorphism. Clinicopathological data and blood samples were taken from all the participants. DNA was extracted and SNPs were confirmed using T-ARMS-PCR protocol. RESULTS: Our data indicated that BRCA1, BRCA2, and TP53 selected SNPs risk allele and risk allele containing genotypes displayed significant association (p < 0.05) with breast cancer risk in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. CONCLUSION: All the three selected SNPs of BRCA1, BRCA2 and TP53 showed significant association with breast cancer risk in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. However, more investigation will be required on large data sets to confirm the selected SNPs and other SNPs in the selected and other related genes with the risk of breast cancer.

Assessment of HER1 (rs11543848) and HER2 (rs1136201) polymorphism and their association with colorectal cancer susceptibility in Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: Colorectal cancer (CRC) is a widespread malignancy characterized by uncontrolled growth in the colon or rectum and remains a leading cause of cancer-related mortality globally. Various genes polymorphisms have been linked with the risk of CRC, but our study aimed to investigate the association between HER1 (rs11543848) and HER2 (rs1136201) polymorphisms with the risk of CRC in the Khyber Pakhtunkhwa (KPK) population of Pakistan. The association of the selected polymorphisms (rs11543848 and rs1136201) with CRC risk has been investigated in various ethnic groups, but their impact remains unexplored in Pakistan, particularly within the KPK population, highlighting the need of the study in this region. METHODS: In this study 120 CRC patients and 120 healthy controls were enrolled. The DNA was extracted from the blood by salting-out method and genotyping was done using ARMS-PCR. RESULTS: Our investigations provided convincing evidence of a strong association between HER1 (rs11543848) and the risk of CRC. Both the genotypes heterozygous GA (OR = 2.07, CI = 1.18 to 3.64, P = 0.01) and homozygous AA (OR = 6.22, CI = 2.56 to 15.08, P = 0.0001) showed higher risk and significant association with the CRC risk. Similarly, heterozygous genotype AG of HER2 (rs1136201) was significantly associated (OR = 3.16, 95% CI = 1.78 to 5.58, P = 0.0001) while mutant genotype GG showed higher risk but non-significant association (OR = 3.23, 95% CI = 0.84 to 12.43, P = 0.08) with CRC patients. HER1 (rs11543848) demonstrated a significant association (P = 0.003) with the age at diagnosis in CRC patients, while HER2 (rs1136201) showed a non-significant association (P = 0.434). Both the SNPs were non-significantly associated with gender (P = 0.793 and 0.117), metastasis (P = 0.582 and 0.129), location of the tumor (P = 0.555 and 0.993), tumor grade (P = 0.290 and 0.920), tumor size (P = 0.535 and 0.289) and stages of cancer (P = 0.892 and 0.352). CONCLUSION: In conclusion, both the polymorphisms rs11543848 and rs1136201 displayed susceptibility with CRC in the KPK population. However, further investigations are recommended while using whole exome sequencing on a larger sample size for more precise results.

Variations in OsSPL10 confer drought tolerance by directly regulating OsNAC2 expression and ROS production in rice.

Drought is a major factor restricting the production of rice (Oryza sativa L.). The identification of natural variants for drought stress-related genes is an important step toward developing genetically improved rice varieties. Here, we characterized a member of the SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) family, OsSPL10, as a transcription factor involved in the regulation of drought tolerance in rice. OsSPL10 appears to play a vital role in drought tolerance by controlling reactive oxygen species (ROS) production and stomatal movements. Haplotype and allele frequency analyses of OsSPL10 indicated that most upland rice and improved lowland rice varieties harbor the OsSPL10Hap1 allele, whereas the OsSPL10Hap2 allele was mainly present in lowland and landrace rice varieties. Importantly, we demonstrated that the varieties with the OsSPL10Hap1 allele showed low expression levels of OsSPL10 and its downstream gene, OsNAC2, which decreases the expression of OsAP37 and increases the expression of OsCOX11, thus preventing ROS accumulation and programmed cell death (PCD). Furthermore, the knockdown or knockout of OsSPL10 induced fast stomatal closure and prevented water loss, thereby improving drought tolerance in rice. Based on these observations, we propose that OsSPL10 confers drought tolerance by regulating OsNAC2 expression and that OsSPL10Hap1 could be a valuable haplotype for the genetic improvement of drought tolerance in rice.

Arsenic level in groundwater and biological samples in Khanewal, Pakistan.

Groundwater is the most valuable natural source in our earth's planet, being contaminated in various regions worldwide. Despite considerable research, there are scarce data regarding arsenic (As) levels in groundwater and its build-up in biological samples in Pakistan. The current investigation analyzed As contamination in four tehsils of District Khanewal (Kabirwala tehsil, Jahaniyan tehsil, Mian Channu tehsil, and Khanewal tehsil). For that, 123 groundwater samples, 19 animal milk samples, 20 human nails, and 20 human hair samples were collected from the study area. Arsenic concentration in groundwater was up to 51.8 µg/L with an average value of 7.2 µg/L. About 28 water samples (23%) had As contents > WHO limit and 38 samples (31%) > DEP-NJ limit. Low levels of As were detected in biological samples. Average As levels were 23 µg/L in the milk samples and 298 µg/kg in human hair. Arsenic contents were not detected in nail samples, except in one sample from Kabirwala tehsil. The maximum values of hazard quotient and cancer risk in District Khanewal were 4.9 and 0.0022, respectively. It is anticipated that long-term use of As-containing water may led to poisoning of humans in the study area, especially in Kabirwala. Therefore, it is necessary to monitor As contamination in the groundwater of Kabirwala tehsil to reduce the potential health hazards.

Dietary organic zinc and probiotic alleviate induced Eimeria tenella infection in Japanese quails model of coccidiosis.

The current study was conducted to evaluate the impact of organic zinc (OZn) and probiotic on growth performance, oocysts number, and histological features of cecum of quails following Eimeria tenella challenge. A total of 480 Japanese quails were distributed into six treatments as follows: untreated uninfected; untreated infected; E. tenella challenge + amprolium; E. tenella challenge + OZn; E. tenella challenge + probiotic; and E. tenella challenge + OZn + probiotic. Except untreated uninfected, all groups were orally gavaged at day 8 with 5 × 104 E. tenella sporulated oocysts. Supplementation of OZn + probiotic improved (P = 0.001) growth performance compared to the untreated infected group. Lesion score of intestine and mortality was lower (P < 0.01) in quails supplemented with OZn + probiotic. Moreover, oocysts per gram (OPG) and histological dimensions of cecum in challenged birds were alleviated in OZn + probiotic. The histological findings of quails supplemented with OZn + probiotic showed normal intestinal villi with gentle sloughed epithelium. We concluded that OZn + probiotic may be safely included in the diet of Japanese quails to control coccidiosis.

RGN1 controls grain number and shapes panicle architecture in rice.

Yield in rice is determined mainly by panicle architecture. Using map-based cloning, we identified an R2R3 MYB transcription factor REGULATOR OF GRAIN NUMBER1 (RGN1) affecting grain number and panicle architecture. Mutation of RGN1 caused an absence of lateral grains on secondary branches. We demonstrated that RGN1 controls lateral grain formation by regulation of LONELY GUY (LOG) expression, thus controlling grain number and shaping panicle architecture. A novel favourable allele, RGN1C , derived from the Or-I group in wild rice affected panicle architecture by means longer panicles. Identification of RGN1 provides a theoretical basis for understanding the molecular mechanism of lateral grain formation in rice; RGN1 will be an important gene resource for molecular breeding for higher yield.

Pollen development in cotton (Gossypium hirsutum) is highly sensitive to heat exposure during the tetrad stage.

The development of gametes in plants is acutely susceptible to heatwaves as brief as a few days, adversely affecting pollen maturation and reproductive success. Pollen in cotton (Gossypium hirsutum) was differentially affected when tetrad and binucleate stages were exposed to heat, revealing new insights into the interaction between heat and pollen development. Squares were tagged and exposed to 36/25°C (day/night, moderate heat) or 40/30°C (day/night, extreme heat) for 5 days. Mature pollen grains and leaves were collected for physiological and proteomic responses. While photosynthetic competence was not compromised even at 40°C, leaf tissues became leakier. In contrast, pollen grains were markedly smaller after the tetrad stage was exposed to 40°C and boll production was reduced by 65%. Sugar levels in pollen grains were elevated after exposure to heat, eliminating carbohydrate deficits as a likely cause of poor reproductive capacity. Proteomic analysis of pure pollen samples revealed a particularly high abundance of 70-kDa heat shock (Hsp70s) and cytoskeletal proteins. While short-term bursts of heat had a minor impact on leaves, male gametophyte development was profoundly damaged. Cotton acclimates to maxima of 36°C at both the vegetative and reproductive stages but 5-days exposure to 40°C significantly impairs reproductive development.

Prevalence of dengue virus serotypes in the 2017 outbreak in Peshawar, KP, Pakistan.

BACKGROUND: Dengue is a viral disease, transmitted by infected Aedes aegypti and Aedes albopictus female mosquitoes. Worldwide, 96 million infections were estimated in 2010. The dengue virus comprises four distinct serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) which belong to the genus Flavivirus. Determining the serotypes during dengue outbreaks is crucial for its effective management in terms of diagnostics improvement and polyvalent vaccine development. The aim of the present study is to determine the prevalence rate of dengue virus serotypes in the samples collected from patients during the 2017 outbreak in Khyber Pakhtunkhwa, Pakistan. METHODS: A total of 800 ELISA-positive samples were collected, of which 513 (290 males, 223 females) samples were confirmed positive by PCR. RESULTS: Out of 513, 25 were found serotype 1 (5%), 196 were serotype 2 (38%), 192 were serotype 3 (37%), 56 were serotype 4 (11%), and 44 (8%) were found to have mix serotypes. CONCLUSION: We can conclude that serotypes 2 and 3 of dengue virus were the predominated serotypes of dengue virus in the 2017 outbreak in Peshawar, capital city of Khyber Pakhtunkhwa, Pakistan.

Hepatitis delta virus and hepatocellular carcinoma: an update.

Hepatitis delta virus (HDV) is a defective RNA virus that depends on the presence of hepatitis B virus (HBV) for the creation of new virions and propagation of the infection to hepatocytes. Chronic infection with HDV is usually associated with a worsening of HBV infection, leading more frequently to cirrhosis, increased risk of liver decompensation and hepatocellular carcinoma (HCC) occurrence. In spite of a progressive declining prevalence of both acute and chronic HDV infection observed over several years, mainly due to increased global health policies and mass vaccination against HBV, several European countries have more recently observed stable HDV prevalence mainly due to migrants from non-European countries. Persistent HDV replication has been widely demonstrated as associated with cirrhosis development and, as a consequence, development of liver decompensation and occurrence of HCC. Several treatment options have been attempted with poor results in terms of HDV eradication and improvement of long-term prognosis. A global effort is deemed urgent to enhance the models already existing as well as to learn more about HDV infection and correlated tumourigenesis mechanisms.