Whole-exome sequencing of Nigerian benign prostatic hyperplasia reveals increased alterations in apoptotic pathways.

BACKGROUND: Through whole-exome sequencing of 60 formalin-fixed paraffin-embedded Nigerian (NGRn) benign prostatic hyperplasia (BPH) samples, we identified germline and somatic alterations in apoptotic pathways impacting BPH development and progression. Prostate enlargement is a common occurrence in male aging; however, this enlargement can lead to lower urinary tract symptoms that negatively impact quality of life. This impact is disproportionately present in men of African ancestry. BPH pathophysiology is poorly understood and studies examining non-European populations are lacking. METHODS: In this study, NGRn BPH, normal prostate, and prostate cancer (PCa) tumor samples were sequenced and compared to characterize genetic alterations in NGRn BPH. RESULTS: Two hundred and two nonbenign, ClinVar-annotated germline variants were present in NGRn BPH samples. Six genes [BRCA1 (92%), HSD3B1 (85%), TP53 (37%), PMS2 (23%), BARD1 (20%), and BRCA2 (17%)] were altered in at least 10% of samples; however, compared to NGRn normal and tumor, the frequency of alterations in BPH samples showed no significant differences at the gene or variant level. BRCA2_rs11571831 and TP53_rs1042522 germline alterations had a statistically significant co-occurrence interaction in BPH samples. In at least two BPH samples, 173 genes harbored somatic variants known to be clinically actionable. Three genes (COL18A1, KIF16B, and LRP1) showed a statistically significant (p < 0.05) higher frequency in BPH. NGRn BPH also had five gene pairs (PKD1/KIAA0100, PKHD1/PKD1, DNAH9/LRP1B, NWD1/DCHS2, and TCERG1/LMTK2) with statistically significant co-occurring interactions. Two hundred and seventy-nine genes contained novel somatic variants in NGRn BPH. Three genes (CABP1, FKBP1C, and RP11-595B24.2) had a statistically significant (p < 0.05) higher alteration frequency in NGRn BPH and three were significantly higher in NGRn tumor (CACNA1A, DMKN, and CACNA2D2). Pairwise Fisher's exact tests showed 14 gene pairs with statistically significant (p < 0.05) interactions and four interactions approaching significance (p < 0.10). Mutational patterns in NGRn BPH were similar to COSMIC (Catalog of Somatic Mutations in Cancer) signatures associated with aging and dysfunctional DNA damage repair. CONCLUSIONS: NGRn BPH contained significant germline alteration interactions (BRCA2_rs11571831 and TP53_rs1042522) and increased somatic alteration frequencies (LMTK2, LRP1, COL18A1, CABP1, and FKBP1C) that impact apoptosis. Normal prostate development is maintained by balancing apoptotic and proliferative activity. Dysfunction in either mechanism can lead to abnormal prostate growth. This work is the first to examine genomic sequencing in NGRn BPH and provides data that fill known gaps in the understanding BPH and how it impacts men of African ancestry.

Whole-exome Sequencing of Nigerian Prostate Tumors from the Prostate Cancer Transatlantic Consortium (CaPTC) Reveals DNA Repair Genes Associated with African Ancestry.

In this study, we used whole-exome sequencing of a cohort of 45 advanced-stage, treatment-naïve Nigerian (NG) primary prostate cancer tumors and 11 unmatched nontumor tissues to compare genomic mutations with African American (AA) and European American (EA) The Cancer Genome Atlas (TCGA) prostate cancer. NG samples were collected from six sites in central and southwest Nigeria. After whole-exome sequencing, samples were processed using GATK best practices. BRCA1 (100%), BARD1 (45%), BRCA2 (27%), and PMS2(18%) had germline alterations in at least two NG nontumor samples. Across 111 germline variants, the AA cohort reflected a pattern [BRCA1 (68%), BARD1 (34%), BRCA2 (28%), and PMS2 (16%)] similar to NG samples. Of the most frequently mutated genes, BRCA1 showed a statistically (P ≤ 0.05) higher germline mutation frequency in men of African ancestry (MAA) and increasing variant frequency with increased African ancestry. Disaggregating gene-level mutation frequencies by variants revealed both ancestry-linked and NG-specific germline variant patterns. Driven by rs799917 (T>C), BRCA1 showed an increasing mutation frequency as African ancestry increased. BRCA2_rs11571831 was present only in MAA, and BRCA2_rs766173 was elevated in NG men. A total of 133 somatic variants were present in 26 prostate cancer-associated genes within the NG tumor cohort. BRCA2 (27%), APC (20%), ATM (20%), BRCA1 (13%), DNAJC6 (13%), EGFR (13%), MAD1L1 (13%), MLH1 (11%), and PMS2 (11%) showed mutation frequencies >10%. Compared with TCGA cohorts, NG tumors showed statistically significant elevated frequencies of BRCA2, APC, and BRCA1. The NG cohort variant pattern shared similarities (cosign similarities ≥0.734) with Catalogue of Somatic Mutations in Cancer signatures 5 and 6, and mutated genes showed significant (q < 0.001) gene ontology (GO) and functional enrichment in mismatch repair and non-homologous repair deficiency pathways. Here, we showed that mutations in DNA damage response genes were higher in NG prostate cancer samples and that a portion of those mutations correlate with African ancestry. Moreover, we identified variants of unknown significance that may contribute to population-specific routes of tumorigenesis and treatment. These results present the most comprehensive characterization of the NG prostate cancer exome to date and highlight the need to increase diversity of study populations. Significance: MAA have higher rates of prostate cancer incidence and mortality, however, are severely underrepresented in genomic studies. This is the first study utilizing whole-exome sequencing in NG men to identify West African ancestry-linked variant patterns that impact DNA damage repair pathways.

First report of Serratia marcescens associated with black rot of Citrus sinensis fruit , and evaluation of its biological control measures in Bangladesh.

Background: The present study was designed to isolate and identify the phyto-pathogen responsible for black rot of Citrus sinensis, and to determine its biological control measures. Methods: The pathogen was isolated from infected oranges and cultured on Luria-Bertani medium. Gram staining method was used to identify the morphological characteristics of the causal agents of the black rot. Advanced molecular technique was applied to facilitate proper detection of the isolated bacteria. Phylogenetic trees were analyzed using the Neighbor-Joining method. Antimicrobial screening was conducted by disc diffusion method. Antagonistic activity was evaluated by well diffusion method. Results: Gram staining of the causal agent showed rod shaped, small and pink bacteria. Polymerase chain reaction of the 16S ribosomal RNA gene amplified an approximately 1465 bp product. The nucleotide sequences of the isolated bacterial sample 1 (BS1) and bacterial sample 2 (BS2) had 99.34% and 99.45% similarities with the reference of Serratia marcescens sequence in NCBI GenBank. The obtained sequences were deposited in GenBank. Two isolates showed virulence capability on some fresh fruits, which confirmed the stain detection and Koch's postulates. Allium sativum extract showed the largest (27.33±1.5 mm) diameter of zone of inhibition against BS1, at 30µg/disc concentration. In the antagonistic assay, Rhizobium leguminosarum showed largest (19±1 mm) zone of inhibition against BS1. Conclusions: Findings of the current investigations are constructive for identification of causative pathogens in Citrus sinensis black rot disease and their biological control measures.

Evaluation of possible biological control of Fusarium concentricum sp. using plant extracts and antagonistic species of microbes in vitro.

Background:Fusarium species is one of the most devastating fungi responsible for fruit and vegetable crops rot worldwide. The present study was designed to find an ecofriendly control measure for pathogenic Fusarium species, using suitable bioagents. Methods: Medicinal plant extracts were evaluated or their antifungal activities against Fusarium species using the poisoned food method. Antagonistic potency of some nonpathogenic microbes was also assessed on Fusarium species using the dual culture method. Results: Highest inhibition of growth of Fusarium sp. was observed with 68.1% (0.389 mg per 90 mm Petri plate) of mycelia on Coccinia grandis plant leaf extract, in comparison to the control grown with 100.0% (1.22 mg/dish). The highest inhibition of radial growth was observed using  Trichoderma viride on Fusarium sp. (46.01% inhibition). Conclusions: The findings of present study would be benevolent for antifungal drug development to control Fusarium sp. causing fruit and vegetable rot.

First report on molecular identification of Fusarium species causing fruit rot of mandarin ( Citrus reticulata) in Bangladesh.

Background: Fusarium rot is a newly introduced, devastating disease of citrus fruits. The current investigation was undertaken to characterize the microbes responsible for fruit rot in Citrus reticulata. Methods: Pathogens were isolated from infected citrus fruits using morphological and molecular approaches. For confirmation of the isolated fungi, polymerase chain reaction (PCR) amplification and internal transcribed spacer gene sequencing techniques were used. Results: The isolated fungus was grown on potato dextrose agar for three days and it produced clamydospores, hyphae and macroconidia. PCR amplification of isolated fungal DNA gave a 650 bp product. The sequence obtained from isolated fungi had 99.42% similarity with the reference Fusarium concentricum sequence in NCBI GenBank. The obtained sequence was deposited in GenBank (Accession No. MT856371). Two isolates showed virulence capability on fresh guava, sweet orange and tomato fruits, which confirmed species identification and Koch's postulates. Artificially inoculated fungal species grown on tested fruits showed typical Fusarium species symptoms. Conclusions: Outcomes of the present study are beneficial for the detection of this detrimental disease in postharvest Citrus reticulata fruits. Further research is needed for the control of this economically important disease. This is the first study of fruit rot in Citrus reticulata caused by Fusarium in Bangladesh.

Profile of children with COVID-19 infection: a cross sectional study from North-East Nigeria.

INTRODUCTION: available evidence suggests that children infected with COVID-19 tend to have a less severe form of the disease. However, most of the studies that have established this largely emanate from outside sub-Saharan Africa. The pandemic nature of the infection makes it instructive to evaluate its pattern among children across different climes, including ours. This study was set out to describe the clinical characteristics of children with COVID-19 in Bauchi State, North-East Nigeria. METHODS: this was a cross sectional study that involved 53 children between the ages of 0 and 18 years, who had RT-PCR confirmed COVID-19 infection between March and June 2020 in Bauchi State, Nigeria. Data on epidemiological and clinical characteristics was analysed using IBM SPSS Statistics V 21.® Relationship between categorical variables was established using the chi square test. The level of statistical significance was set at < 0.05, at a confidence interval (CI) of 95%. RESULTS: the mean age was 12.63 ± 4.31 years with a slight preponderance of males (1.1: 1). Majority were asymptomatic (60.4%), while 32.1% and 7.5% had mild and moderate diseases respectively. The most common symptoms were cough (20.8%), fever (17%), and sneezing (15.1%). Five children (9.4%) complained of loss of taste while anosmia was documented in one child (1.9%). We observed a significant relationship between age category and the presence of symptoms. In fact, children younger than 10 years (pre-adolescents) were five times more likely to be symptomatic when compared to those above this age (p = 0.029, C I 1.08-21.56). CONCLUSION: our findings have shown a mild pattern of disease and good outcome among infected children. However, we must be mindful of the higher vulnerability among younger children, especially those below 10 years.

Prevalence and correlates of stunting among the school-age population in North-Central Nigeria.

INTRODUCTION: Stunting remains a huge public health concern among developing Nations. However, the burden of this problem among the school-age population appears to have been eclipsed by most nutritional surveys that focus more on the under-fives. This study aimed to demonstrate the prevalence, and identify socio-demographic factors that are associated with stunting among the school-age children in North central Nigeria. METHODS: This was a descriptive cross-sectional study that involved 450 pupils, aged 6-12 years from 10 randomly selected primary schools in Jos, Plateau state. Anthropometric indices were measured using standard techniques and the Height-for-age z-scores were generated using the WHO Anthroplus software. Socio-demographic details were obtained using semi-structured questionnaires. Data were analysed using EPI infoTM statistical software 7.1.5.2. RESULTS: The mean age of the subjects was 9.3 ± 1.8 years and the male to female ratio was 1:1.1. The prevalence of stunting was 10.5%. The prevalence of stunting was significantly higher among pupils that attended public schools (p<0.0001), those whose mothers had less than secondary level of education (p=0.0427), those between the ages of 10-12 years (p<0.0001), those from the lower socio-economic class (p=0.0021), and those whose family sizes were larger than six family members (p=0.0063). CONCLUSION: The substantial burden of stunting among the school age population has significant correlation with certain socio-demographic factors. Addressing these factors by alleviating poverty, promoting maternal literacy and encouraging family planning may, perhaps, lessen the burden of stunting among the school-age group in Northern Nigeria.