Hemoglobin A1c (HbA1c) is widely used to diagnose diabetes and assess glycemic control in individuals with diabetes. However, nonglycemic determinants, including genetic variation, may influence how ...accurately HbA1c reflects underlying glycemia. Analyzing the NHLBI Trans-Omics for Precision Medicine (TOPMed) sequence data in 10,338 individuals from five studies and four ancestries (6,158 Europeans, 3,123 African-Americans, 650 Hispanics, and 407 East Asians), we confirmed five regions associated with HbA1c (GCK in Europeans and African-Americans, HK1 in Europeans and Hispanics, FN3K and/or FN3KRP in Europeans, and G6PD in African-Americans and Hispanics) and we identified an African-ancestry-specific low-frequency variant (rs1039215 in HBG2 and HBE1, minor allele frequency (MAF) = 0.03). The most associated G6PD variant (rs1050828-T, p.Val98Met, MAF = 12% in African-Americans, MAF = 2% in Hispanics) lowered HbA1c (−0.88% in hemizygous males, −0.34% in heterozygous females) and explained 23% of HbA1c variance in African-Americans and 4% in Hispanics. Additionally, we identified a rare distinct G6PD coding variant (rs76723693, p.Leu353Pro, MAF = 0.5%; −0.98% in hemizygous males, −0.46% in heterozygous females) and detected significant association with HbA1c when aggregating rare missense variants in G6PD. We observed similar magnitude and direction of effects for rs1039215 (HBG2) and rs76723693 (G6PD) in the two largest TOPMed African American cohorts, and we replicated the rs76723693 association in the UK Biobank African-ancestry participants. These variants in G6PD and HBG2 were monomorphic in the European and Asian samples. African or Hispanic ancestry individuals carrying G6PD variants may be underdiagnosed for diabetes when screened with HbA1c. Thus, assessment of these variants should be considered for incorporation into precision medicine approaches for diabetes diagnosis.
PHAs are biodegradable and environmentally friendly thermoplastics. The major contributor to PHA production cost is carbon substrate cost, therefore it is desirable to produce PHA from ...waste/byproducts like
Jatropha biodiesel byproducts.
This study was done using
Jatropha biodiesel byproduct as carbon source, to decrease production cost for PHAs. Total 41 isolates from soil and marine source were able to utilize
Jatropha biodiesel byproduct. Nine bacteria were selected for further studies, which were found positive for Nile red viable colony screening. Two bacterial isolates SM-P-1S and SM-P-3M isolated from soil and marine environment respectively, were found promising for PHA production. PHA accumulation for SM-P-1S and SM-P-3M was 71.8% and 75% PHA/CDW respectively and identified as
Bacillus sonorensis and
Halomonas hydrothermalis by MTCC. The PHA obtained from SM-P-1S and SM-P-3M was analyzed by FTIR and NMR as polyhydroxybutyrate (PHB).
Bg_9562, a prophage tail-like protein was earlier shown to be required for bacterial mycophagy by Burkholderia gladioli strain NGJ1. The purified protein exhibited broad-spectrum antifungal activity; ...however, the structural and mechanistic details vis-à-vis its activity remained elusive. In this study, we have structurally characterized the protein Bg_9562 using negatively stained transmission electron microscopy, molecular modeling and mutagenesis. We find that Bg_9562 shows structural similarity to Gp13, a tail assembly chaperone. The transmission electron microscopy revealed that, Bg_9562 forms long flexible tubular structures. Molecular modeling of the filament like structure divulges that the inter subunit contacts are meditated largely through hydrophobic interactions. Using mutagenesis, we demonstrate that the N-terminal residues of the protein when deleted results in reduced activity and destabilization of filament formation. Overall, structure-function analysis opens up avenues for further utilization of the protein as a potent antifungal molecule.
Burkholderia gladioli strain NGJ1, isolated from healthy rice seedling, was earlier demonstrated to have mycophagous properties on a broad range of fungi, including Rhizoctonia solani, a causal agent of deadly sheath blight disease of rice. The purified Bg_9562 protein exerts broad-spectrum antifungal activity. The protein also inhibits the growth of laboratory strain of Candida, an opportunistic human pathogen. In this study, we structurally characterize Bg_9562 using a combination of negative staining transmission electron microscopy, molecular modeling, mutagenesis, and functional antifungal assay. We show that the protein assembles into long filament like structures stabilized by N-terminus residues and this region is important for its activity. Our study has implications in utilizing Bg_9562 or its derivatives as antifungal molecule(s) which will provide environmentally friendly control of fungal diseases of plants and animals.
Prior GWAS have identified loci associated with red blood cell (RBC) traits in populations of European, African, and Asian ancestry. These studies have not included individuals with an Amerindian ...ancestral background, such as Hispanics/Latinos, nor evaluated the full spectrum of genomic variation beyond single nucleotide variants. Using a custom genotyping array enriched for Amerindian ancestral content and 1000 Genomes imputation, we performed GWAS in 12,502 participants of Hispanic Community Health Study and Study of Latinos (HCHS/SOL) for hematocrit, hemoglobin, RBC count, RBC distribution width (RDW), and RBC indices. Approximately 60% of previously reported RBC trait loci generalized to HCHS/SOL Hispanics/Latinos, including African ancestral alpha- and beta-globin gene variants. In addition to the known 3.8kb alpha-globin copy number variant, we identified an Amerindian ancestral association in an alpha-globin regulatory region on chromosome 16p13.3 for mean corpuscular volume and mean corpuscular hemoglobin. We also discovered and replicated three genome-wide significant variants in previously unreported loci for RDW (SLC12A2 rs17764730, PSMB5 rs941718), and hematocrit (PROX1 rs3754140). Among the proxy variants at the SLC12A2 locus we identified rs3812049, located in a bi-directional promoter between SLC12A2 (which encodes a red cell membrane ion-transport protein) and an upstream anti-sense long-noncoding RNA, LINC01184, as the likely causal variant. We further demonstrate that disruption of the regulatory element harboring rs3812049 affects transcription of SLC12A2 and LINC01184 in human erythroid progenitor cells. Together, these results reinforce the importance of genetic study of diverse ancestral populations, in particular Hispanics/Latinos.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A 60-year-old male patient diagnosed with mucinous adenocarcinoma of lower third of rectum underwent abdominoperineal resection and permanent colostomy followed by adjuvant chemotherapy. Response ...evaluation with F-18 FDG PET-CT showed a complete metabolic response. After 6 months, CEA levels started increasing and clinically a recurrence was suspected. A restaging FDG PET-CT showed no obvious malignant disease. Patient presented again within a month with complaints of urinary retention and haematuria. CEA levels were further elevated, and Ga-68 FAPI-04 (FAPI) PET-CT was performed. FAPI PET-CT revealed prostatic and seminal vesicle disease involvement. Additionally, an MRI of pelvis was done and fused with FAPI PET for confirmation of prostatic involvement.
Key message
FAPI PET-CT can help diagnose clinically challenging difficult cases.
Dental caries is the most common chronic disease worldwide, and exhibits profound disparities in the USA with racial and ethnic minorities experiencing disproportionate disease burden. Though ...heritable, the specific genes influencing risk of dental caries remain largely unknown. Therefore, we performed genome-wide association scans (GWASs) for dental caries in a population-based cohort of 12 000 Hispanic/Latino participants aged 18-74 years from the HCHS/SOL. Intra-oral examinations were used to generate two common indices of dental caries experience which were tested for association with 27.7 M genotyped or imputed single-nucleotide polymorphisms separately in the six ancestry groups. A mixed-models approach was used, which adjusted for age, sex, recruitment site, five principal components of ancestry and additional features of the sampling design. Meta-analyses were used to combine GWAS results across ancestry groups. Heritability estimates ranged from 20-53% in the six ancestry groups. The most significant association observed via meta-analysis for both phenotypes was in the region of the NAMPT gene (rs190395159; P-value = 6 × 10(-10)), which is involved in many biological processes including periodontal healing. Another significant association was observed for rs72626594 (P-value = 3 × 10(-8)) downstream of BMP7, a tooth development gene. Other associations were observed in genes lacking known or plausible roles in dental caries. In conclusion, this was the largest GWAS of dental caries, to date and was the first to target Hispanic/Latino populations. Understanding the factors influencing dental caries susceptibility may lead to improvements in prediction, prevention and disease management, which may ultimately reduce the disparities in oral health across racial, ethnic and socioeconomic strata.
C-Phycoerythrin is water soluble red color chromo-protein, which is used as a natural food colorant. The effect of selected edible preservatives like citric acid, sodium chloride, sucrose and calcium ...chloride on the stability of C-Phycoerythrin at 0
±
5
°C and 35
±
5
°C was studied in aqueous solution. Experiment was carried out to select a stabilizing agent having Hofmeister series behavior acting on hydrophobic interactions. The denaturation of phycoerythrin with urea as denaturant and effect of different pH on C-Phycoerythrin was studied. Citric acid (4
mg/ml) was observed to be one of the best preservative for C-Phycoerythrin at 35
±
5
°C and 0
±
5
°C in aqueous solution for 45 days. Citric acid was able to maintain the stability of C-Phycoerythrin in the solution. The amount of C-Phycoerythrin left in the solution containing citric acid after 30 and 45 days was 46 and 37.8% respectively at higher temperature.
Regulated gene expression controls organismal development, and variation in regulatory patterns has been implicated in complex traits. Thus accurate prediction of enhancers is important for further ...understanding of these processes. Genome-wide measurement of epigenetic features, such as histone modifications and occupancy by transcription factors, is improving enhancer predictions, but the contribution of these features to prediction accuracy is not known. Given the importance of the hematopoietic transcription factor TAL1 for erythroid gene activation, we predicted candidate enhancers based on genomic occupancy by TAL1 and measured their activity. Contributions of multiple features to enhancer prediction were evaluated based on the results of these and other studies.
TAL1-bound DNA segments were active enhancers at a high rate both in transient transfections of cultured cells (39 of 79, or 56%) and transgenic mice (43 of 66, or 65%). The level of binding signal for TAL1 or GATA1 did not help distinguish TAL1-bound DNA segments as active versus inactive enhancers, nor did the density of regulation-related histone modifications. A meta-analysis of results from this and other studies (273 tested predicted enhancers) showed that the presence of TAL1, GATA1, EP300, SMAD1, H3K4 methylation, H3K27ac, and CAGE tags at DNase hypersensitive sites gave the most accurate predictors of enhancer activity, with a success rate over 80% and a median threefold increase in activity. Chromatin accessibility assays and the histone modifications H3K4me1 and H3K27ac were sensitive for finding enhancers, but they have high false positive rates unless transcription factor occupancy is also included.
Occupancy by key transcription factors such as TAL1, GATA1, SMAD1, and EP300, along with evidence of transcription, improves the accuracy of enhancer predictions based on epigenetic features.
•Significant reduction in AR and PR receptor expression observed in patients undergoing progesterone therapy.•African American (AA) patients had notably greater decline in AR scores post-treatment ...compared to non-AA patients.•Changes in steroid receptor expression showed no correlation with BMI or smoking status.•Changes in steroid receptor expression may be a promising prognostic biomarker for response to progestin therapy.
Conservative management of atypical endometrial hyperplasia (AEH) or endometrial cancer (EMCA) often relies on the treatment of synthetic progestins, which show varied success and response rates. We evaluate the correlation between steroid receptor expression and response to progestin therapy in patients with AEH and EMCA.
Retrospective cohort study collected data for patients with AEH or EMCA who had an endometrial sample after receiving conservative therapy utilizing either Megestrol acetate or Levonorgestrel Intrauterine device (IUD). Immunohistochemistry (IHC) was performed on pre- and post- treatment biopsy samples to assess androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PR) expression. IHC scores (1–12) were calculated based on staining intensity and percentage of positive cells.
We identified 15 patients with AEH and EMCA between 2015 and 2023 with the majority of African American ethnicity (53 %). Fourteen patients (93 %) received Megestrol acetate, and 1 patient received Levonorgestrel IUD alone. Three patients ultimately underwent hysterectomy. Seven (46.6 %) endometrial samples had strong positivity for AR, PR and ER expression on pre-treatment biopsies, and only 3 (20 %) of them maintained strong positivity for the 3 receptors in the post-treatment. Patients who successfully responded to the treatment demonstrated a significantly greater decrease in IHC scores after the treatment compared to those who did not respond (p = 0.009).
Steroid receptor expression could be used as a possible biomarker for response to progestin therapy in patients undergoing conservative management for AEH and EMCA.
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