Challenges and Counteracting Strategies Including Optimum Health Service Practices for Frontline Nurses During the Mpox Outbreak and Futuristic Vision.

Introduction: Monkeypox (mpox) is an evolving infectious disease caused by the monkeypox virus (MPXV). On July 23, 2022, the WHO declared the recent mpox outbreaks a public health emergency of international concern (PHEIC), which terminated on May 11, 2023. As of July 11, 2023, 88,288 confirmed cases and 149 deaths have been reported from 112 countries and territories. Currently, mpox is not a PHEIC, as the outbreak and its impacts are nearly over. Nurses played significant roles during the mpox 2022 outbreak as frontline workers. Purpose: In light of the impending mpox global outbreak in 2022, this brief report provides an update on the enormous difficulties faced by frontline nurses while playing a crucial role in handling the mpox outbreak and some potential solutions to these difficulties. The methodological framework employed in this narrative brief report involves conducting a comprehensive analysis and synthesis of relevant literature and hypothetical scenarios. The aim is to put forth practical strategies that can effectively tackle the difficulties encountered by frontline nurses in the context of the mpox outbreak. Additionally, the report seeks to envision a healthcare system that is more resilient in the face of future challenges. Conclusion: It is important to understand the challenges the nurses face from their perspective. As frontline health care workers, the various health issues of nurses and their concerns must be taken care of appropriately by adopting optimum health service practices, adequate safety measures, recommended precautionary measures, and boosting them mentally while handling mpox patients. Counseling and the arrangement of workshops are required. Appropriate care should be taken to address the various health issues concerning nurses by adopting health service practices at optimum levels. Side by side, recommended safety and precautionary measures should be followed.

Oral decitabine and cedazuridine plus venetoclax for older or unfit patients with acute myeloid leukaemia: a phase 2 study.

BACKGROUND: Hypomethylating agents combined with venetoclax are effective regimens in patients with acute myeloid leukaemia who are ineligible for intensive chemotherapy. Decitabine and cedazuridine (ASTX727) is an oral formulation of decitabine that achieves equivalent area-under-curve exposure to intravenous decitabine. We performed a single centre phase 2 study to evaluate the efficacy and safety of ASTX727 plus venetoclax. METHODS: This study enrolled patients with newly diagnosed (frontline treatment group) acute myeloid leukaemia who were ineligible for intensive chemotherapy (aged ≥75 years, an Eastern Cooperative Oncology Group [ECOG] performance status of 2-3, or major comorbidities) or relapsed or refractory acute myeloid leukaemia. Being aged 18 years or older and having an ECOG performance status of 2 or less were requirements for the relapsed or refractory disease treatment cohort, without any limits in the number of previous lines of therapy. Treatment consisted of ASTX727 (cedazuridine 100 mg and decitabine 35 mg) orally for 5 days and venetoclax 400 mg orally for 21-28 days in 28-day cycles. The primary outcome was overall response rate of ASTX727 plus venetoclax. Living patients who have not completed cycle one were not evaluable for response. Safety was analysed in all patients who started treatment. This study was registered on ClinicalTrials.gov (NCT04746235) and is ongoing. The data cutoff date for this analysis was Sept 22, 2023. FINDINGS: Between March 16, 2021, and Sept 18, 2023, 62 patients were enrolled (49 frontline and 13 relapsed or refractory) with a median age of 78 years (IQR 73-82). 36 (58%) were male; 53 (85%) were White, 4 (6%) Black, 2 (3%) Asian and 3 (5%) other or did not answer. 48 (77%) of 62 patients were European LeukemiaNet 2022 adverse risk, 24 (39%) had antecedent myelodysplastic syndromes, 12 (19%) had previously failed a hypomethylating agent, ten (16%) had therapy-related acute myeloid leukaemia, and 11 (18%) had TP53 mutations. The median follow-up time was 18·3 months (IQR 8·8-23·3). The overall response rate was 30 (64%) of 47 patients (95% CI 49-77) in frontline cohort and six (46%) of 13 patients (19-75) in relapsed or refractory cohort. The most common grade 3 or worse treatment-emergent adverse events were febrile neutropenia in 11 (18%) of 62 patients, pneumonia in eight (13%), respiratory failure in five (8%), bacteraemia in four (6%), and sepsis in four (6%). Three deaths occurred in patients in remission (one sepsis, one gastrointestinal haemorrhage, and one respiratory failure) and were potentially treatment related. INTERPRETATION: ASTX727 plus venetoclax is an active fully oral regimen and safe in most older or unfit patients with acute myeloid leukaemia. Our findings should be confirmed in larger multicentric studies. FUNDING: MD Anderson Cancer Center Support Grant, Myelodysplastic Syndrome/Acute Myeloid Leukaemia Moon Shot, Leukemia SPORE, Taiho Oncology, and Astex Pharmaceuticals.

Long-term trends in the work hours of physicians in Canada.

BACKGROUND: Physician work hours directly influence patient access to health care services and play a vital role in physician human resource planning. We sought to evaluate long-term trends in hours worked by physicians in Canada, overall and by subgroup. METHODS: We used Statistics Canada's Labour Force Survey to identify physicians via occupation and industry coding information. We estimated descriptive statistics and performed graphical analysis of the average weekly hours worked by physicians over the 1987-2021 period. RESULTS: Overall, weekly physician work hours remained stable from 1987 until 1997, after which they declined. Average weekly hours decreased by 6.9 hours (p < 0.001), from 52.8 in 1987-1991 to 45.9 in 2017-2021. Among male physicians, work hours declined notably after 1997, while those of female physicians remained relatively stable at around 45 per week. Hours worked by married physicians declined significantly, amounting to 7.4 fewer hours per week (p = 0.001). In contrast, unmarried physicians displayed a statistically insignificant decline of 2.2 hours (p = 0.3). The COVID-19 pandemic was associated with a sharp but brief disruption in weekly hours; by the end of 2020, physicians' work hours had returned to prepandemic levels. INTERPRETATION: These findings may indicate a long-term shift in work preferences among Canadian physicians; male physicians may be seeking a better work-life balance, which, in turn, has narrowed the gap in hours worked by sex, with potential implications for pay equity. Policymakers and planners should carefully consider changes in hours worked, rather than just the total number of physicians, to ensure an accurate evaluation of the physician workforce.

Extension of shelf life of Nile tilapia (Oreochromis niloticus) fillets using seaweed extracts during refrigerated storage.

The effects of seaweed (Padina tetrastromatica, Sargassum natans, and Sargassum fluitans) ethanolic extracts on the quality and shelf life extension of Nile tilapia (Oreochromis niloticus) fillets were investigated during refrigerated storage for 20 days. Each of the seaweed ethanolic extracts solution (2%, w/v) was used for dipping the fish fillets for 10 min at 4°C. The control and seaweed extract-treated fillets were stored at 4 ± 1°C in air-tight polyethylene bags, and chemical, bacteriological, and sensory evaluation were performed at every 4 days' intervals. During the storage period, P. tetrastromatica extract significantly (p < .05) reduced the increment of pH, peroxide value, thiobarbituric acid reactive substances, and total volatile basic nitrogen values in Nile tilapia fillets compared to other seaweed extracts-treated and untreated fillets. The maximal total viable count of control, P. tetrastromatica, S. natans, and S. fluitans extracts-treated fillets was 6.53, 7.11, 6.75, and 7.10 log CFU/g at the 8th, 20th, 12th, and 16th days of storage, respectively. The total psychrotrophic count of control and seaweed extracts-treated fillets was also significantly increased (p < .05) throughout the storage period. The P. tetrastromatica extracts-treated fillets showed better sensory characteristics than other seaweed extracts-treated and control fillets. Results of this study suggest that ethanolic extracts (2%, w/v) of P. tetrastromatica extend the shelf life for 12 days longer than the control fillets in refrigerated conditions.

Phase II study of cladribine, idarubicin, and ara-C (CLIA) with or without sorafenib as initial therapy for patients with acute myeloid leukemia.

The addition of cladribine, or sorafenib to standard chemotherapy have each demonstrated improved survival in patients with newly-diagnosed acute myeloid leukemia (AML). We studied the combination of cladribine, idarubicin, and intermediate-dose cytarabine (CLIA) in patients ≤65 years of age with newly diagnosed AML, fit to receive intensive therapy. Cladribine (5 mg/m2) IV was administered on days (D)1-5, cytarabine (1 g/m2) on D1-5, and idarubicin (10 mg/m2) on D1-3. Sorafenib was added to the CLIA backbone for patients with FLT3-ITD mutated AML. 80 patients were enrolled: 65 with newly diagnosed AML and 15 with AML arising from previously treated MDS (ts-AML). The median age was 55 years (range, 21-65). CR + CRi was 83% (54/65) and 27% in the untreated and ts-AML cohorts, respectively; 74% and 75% of responding patients, respectively, had undetectable measurable residual disease (MRD). Among patients with FLT3-ITD mutated AML receiving CLIA+sorafenib, the CR + CRi rate was 95%, with 81% negative for MRD. With a median follow-up of 76 months, the 2- and 4-year OS of 57% and 50% compared to 20%, and 13% for ts-AML, respectively. Patients treated with CLIA+sorafenib had 2- and 5-year OS rates of 63% and 59%, respectively. The most common Grade ≥3 adverse events were infection/fever, elevated bilirubin, rash, and nausea. CLIA was safe and effective in young, fit patients with newly diagnosed AML with inferior outcomes among patients with ts-AML. The addition of sorafenib to CLIA in FLT3-ITD mutated AML resulted in high rates of durable remission and excellent long-term survival.

Association of household fuel use with hypertension and blood pressure among adult women in rural Bangladesh: A cross-sectional study.

OBJECTIVES: This study aimed to determine the association of household fuel use with hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP) among adult women. METHODS: A cross-sectional survey through face-to-face interviews and blood pressure (BP) measurement were conducted among 2182 randomly selected women (1236 solid fuel users and 946 clean fuel users) in rural areas of Bangladesh. RESULTS: Overall, 21% of women were hypertensive. Mean SBP and DBP for the study population were 121.27 mmHg (SD ± 15.43) and 76.18 mmHg (SD ± 12.00), respectively. Hypertension was found significantly (p = .006) higher among solid fuel users (23%) compared to clean fuel users (18%). Women using solid fuels have a 35% higher chance (AOR: 1.35, CI: 1.10-1.80) of having hypertension and have more than twice the risk of developing elevated SBP (AOR: 2.01, CI: 1.55-2.95) relative to women using clean fuels for their daily cooking. The probability of hypertension (AOR: 1.39, CI: 1.17-1.60) and elevated SBP (AOR: 1.35, CI: 1.10-1.61) increased significantly for every hour of fuel use. CONCLUSIONS: Using clean fuel, reducing the duration of daily cooking time, and improved cooking facilities may help minimizing hypertension and ultimately cardiovascular disease risk among women.

The assessment of musculoskeletal disorders, quality of life, and comorbidities in older people in Bangladesh.

Musculoskeletal disorders are debilitating conditions that significantly impact the state of health, especially in older people. The study, which employed a cross-sectional design and practical sampling, included 206 participants among them 124 (62.2%) were men and 82 (39.8%) were women, from all over Bangladesh with musculoskeletal issues of varying severity and impact. The mean age of the participants was 64.9 (SD 4.3). The study was carried out between January and June of 2022. The majority of participants experienced musculoskeletal pain. Back pain was the most commonly complained of symptom among the participants (74.9%). It was also common to have limited mobility as a result of arthritic change, which eventually affected daily activities like taking care of oneself. To improve the health of the older adult population, more studies must be conducted to identify the many factors that contribute to musculoskeletal issues. The development of effective prevention and rehabilitation programs must then be based on this knowledge.

Genome Divergence and Dynamics in the Thin-Tailed Desert Sheep From Sudan.

With climate change bound to affect food and feed production, emphasis will shift to resilient and adapted indigenous livestock to sustain animal production. However, indigenous livestock comprise several varieties, strains and ecotypes whose genomes are poorly characterized. Here, we investigated genomic variation in an African thin-tailed Desert Sheep sampled in Sudan, using 600K genotype data generated from 92 individuals representing five ecotypes. We included data from 18 fat-tailed and 45 thin-tailed sheep from China, to investigate shared ancestry and perform comparative genomic analysis. We observed a clear genomic differentiation between the African thin-tailed Desert Sheep and the Chinese thin-tailed and fat-tailed sheep, suggesting a broad genetic structure between the fat-tailed and thin-tailed sheep in general, and that at least two autosomal gene pools comprise the genome profile of the thin-tailed sheep. Further analysis detected two distinct genetic clusters in both the African thin-tailed Desert Sheep and the Chinese thin-tailed sheep, suggesting a fine-scale and complex genome architecture in thin-tailed sheep. Selection signature analysis suggested differences in adaptation, production, reproduction and morphology likely underly the fine-scale genetic structure in the African thin-tailed Desert Sheep. This may need to be considered in designing breeding programs and genome-wide association studies.

Venetoclax plus intensive chemotherapy with cladribine, idarubicin, and cytarabine in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a cohort from a single-centre, single-arm, phase 2 trial.

BACKGROUND: Addition of the BCL2 inhibitor venetoclax to lower intensity therapy has been shown to improve overall survival in older (aged 75 years or older) and unfit patients with newly diagnosed acute myeloid leukaemia. The aim of this study was to investigate the activity of venetoclax combined with intensive chemotherapy in patients aged 65 years or younger with acute myeloid leukaemia. METHODS: This cohort study was done at the MD Anderson Cancer Center in the USA, as part of the single-centre, single arm, phase 2, CLIA trial. Here we report on the independent cohort investigating the safety and activity of venetoclax added to intensive chemotherapy (the CLIA regimen [cladribine, high-dose cytarabine, idarubicin]). Eligible patients were aged 18-65 years with a new diagnosis of acute myeloid leukaemia, mixed phenotype acute leukaemia, or high-risk myelodysplastic syndrome (≥10% blasts or International Prognostic Scoring System ≥2 [intermediate]), who received no previous potentially curative therapy for leukaemia. Patients received cladribine (5 mg/m2) and cytarabine (1·5 g/m2 for patients aged <60 years, 1 g/m2 for patients aged ≥60 years) intravenously on days 1-5 and idarubicin (10 mg/m2) intravenously on days 1-3. Consolidation was cladribine (5 mg/m2) and cytarabine (1 g/m2 for patients aged <60 years and 0·75 g/m2 for patients aged ≥60 years) on days 1-3 and idarubicin (8 mg/m2) on days 1-2. Venetoclax (400 mg) was given on days 2-8 with each course. Patients with a known FLT3-ITD or FLT3-TKD mutation received midostaurin or gilteritinib. The primary outcome was composite complete response (complete response plus complete response with incomplete blood count recovery). Secondary outcomes were overall response, duration of response, event-free survival, overall survival, and safety. This trial was registered with ClinicalTrials.gov, NCT02115295. FINDINGS: Between Feb 25, 2019, and March 23, 2021, 77 patients were assessed for eligibility, 50 of whom were enrolled. Median age was 48 years (IQR 37-56). 47 (94% [95% CI 83-98]) patients had composite complete response, with the same proportion also having an overall response; two (4% [1-14]) patients did not respond, and one (2% [0-11]) patient died during induction. 37 (82% [95% CI 68-92]) of 45 patients had undetectable measurable residual disease (MRD). At a median follow-up of 13·5 months (IQR 6·4-19·5), the median duration of response, event-free survival, and overall survival were not reached. At 12 months, the estimated duration of response was 74% (95% CI 60-92), event-free survival was 68% (54-85), and overall survival was 85% (75-97). The most common adverse events of grade 3 or worse were febrile neutropenia (42 [84%] patients), infection (six [12%]), and alanine aminotransferase elevations (six [12%]). There was one death during induction in a patient treated with CLIA-venetoclax plus a FLT3 inhibitor. Two patients died of infectious complications while in complete response in consolidation cycles, both of whom had FLT3-mutated acute myeloid leukaemia and were receiving combined therapy with a FLT3 inhibitor. No deaths were deemed to be treatment related. INTERPRETATION: Venetoclax added to CLIA was safe and active in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome, producing high rates of durable MRD-negative remissions and encouraging event-free survival and overall survival. FUNDING: MD Anderson Cancer Center.

Screening and Mapping for Head Blast Resistance in a Panel of CIMMYT and South Asian Bread Wheat Germplasm.

Wheat blast (WB) is a destructive disease in South America and its first outbreak in Bangladesh in 2016 posed a great risk to food security of South Asian countries. A genome wide association study (GWAS) was conducted on a diverse panel of 184 wheat genotypes from South Asia and CIMMYT. Phenotyping was conducted in eight field experiments in Bolivia and Bangladesh and a greenhouse experiment in the United States. Genotypic data included 11,401 SNP markers of the Illumina Infinium 15K BeadChip and four additional STS markers on the 2NS/2AS translocation region. Accessions with stable WB resistance across experiments were identified, which were all 2NS carriers. Nevertheless, a dozen moderately resistant 2AS lines were identified, exhibiting big variation among experiments. Significant marker-trait associations (MTA) were detected on chromosomes 1BS, 2AS, 6BS, and 7BL; but only MTAs on 2AS at the 2NS/2AS translocation region were consistently significant across experiments. The resistant accessions identified in this study could be used in production in South Asian countries as a preemptive strategy to prevent WB outbreak.

Synthesis of biodiesel from chicken skin waste: an economic and environmental biofuel feedstock in Bangladesh.

One of the dominating meat supply industries, the poultry chicken sector, is facing waste management concerns worldwide. Due to high oil content containment, biofuel researchers emphasized poultry waste as abundant, cheap, and high-quality feedstock for biodiesel production. Therefore, in the current study, an experimental investigation of biodiesel production from wasted chicken skin through the transesterification process has been performed. The chicken skin used in this study for biodiesel production can be used as the potential waste source for biodiesel production worldwide. Techno-economic, environmental, and sustainability analyses were also performed. During the synthesis, the reaction was conducted with potassium hydroxide (KOH), and the process yielded 48% biodiesel. The cost of electricity for providing electricity is estimated at US$0.575 per kWh when an auto-sized generator has been fueled by biodiesel. The environmental and substantiality analysis found that biodiesel is more suitable than conventional diesel as an environmentally friendly and sustainable fuel.

Correction: Genomic mapping identifies two genetic variants in the MC1R gene for coat colour variation in Chinese Tan sheep.

[This corrects the article DOI: 10.1371/journal.pone.0235426.].

Genomic Selection for Wheat Blast in a Diversity Panel, Breeding Panel and Full-Sibs Panel.

Wheat blast is an emerging threat to wheat production, due to its recent migration to South Asia and Sub-Saharan Africa. Because genomic selection (GS) has emerged as a promising breeding strategy, the key objective of this study was to evaluate it for wheat blast phenotyped at precision phenotyping platforms in Quirusillas (Bolivia), Okinawa (Bolivia) and Jashore (Bangladesh) using three panels: (i) a diversity panel comprising 172 diverse spring wheat genotypes, (ii) a breeding panel comprising 248 elite breeding lines, and (iii) a full-sibs panel comprising 298 full-sibs. We evaluated two genomic prediction models (the genomic best linear unbiased prediction or GBLUP model and the Bayes B model) and compared the genomic prediction accuracies with accuracies from a fixed effects model (with selected blast-associated markers as fixed effects), a GBLUP + fixed effects model and a pedigree relationships-based model (ABLUP). On average, across all the panels and environments analyzed, the GBLUP + fixed effects model (0.63 ± 0.13) and the fixed effects model (0.62 ± 0.13) gave the highest prediction accuracies, followed by the Bayes B (0.59 ± 0.11), GBLUP (0.55 ± 0.1), and ABLUP (0.48 ± 0.06) models. The high prediction accuracies from the fixed effects model resulted from the markers tagging the 2NS translocation that had a large effect on blast in all the panels. This implies that in environments where the 2NS translocation-based blast resistance is effective, genotyping one to few markers tagging the translocation is sufficient to predict the blast response and genome-wide markers may not be needed. We also observed that marker-assisted selection (MAS) based on a few blast-associated markers outperformed GS as it selected the highest mean percentage (88.5%) of lines also selected by phenotypic selection and discarded the highest mean percentage of lines (91.8%) also discarded by phenotypic selection, across all panels. In conclusion, while this study demonstrates that MAS might be a powerful strategy to select for the 2NS translocation-based blast resistance, we emphasize that further efforts to use genomic tools to identify non-2NS translocation-based blast resistance are critical.

Relaxing music reduces blood pressure and heart rate among pre-hypertensive young adults: A randomized control trial.

Prevalence of pre-hypertension is higher among young adults and may increase the risk for hypertension and cardiovascular morbidity. Music therapy has been investigated to reduce the blood pressure in the hypertensive population; however, its efficacy on blood pressure in pre-hypertensive young adults is not known. Thirty pre-hypertensive (systolic blood pressure [SBP] = 120-139 mmHg and diastolic blood pressure [DBP] = 80-89 mmHg) young adults were recruited and randomly assigned into two groups. Music group (N = 15) received music therapy by passive listening to music for 30 minutes/day, 5 days/week for 4 weeks, along with Dietary Approaches to Stop Hypertension (DASH) eating plan (a diet rich in fruits and vegetables, low-fat dairy or unsaturated fat) and limit the daily sodium intake less than 100 mmol/day. The control group (N = 15) practiced only DASH eating plan and sodium restriction. The SBP, DBP, and heart rate (HR) were measured before and after 4 weeks of intervention. There was a significant reduction in SBP (8.73 mmHg, p < .001) and HR (6.42 beats/minute, p = .002); however, the reduction in DBP (1.44 mmHg, p = .101) was not statistically significant in the music group. Control group did not exhibit any significant reduction in SBP (0.21 mmHg, p < .836), DBP (0.81 mmHg, p < .395) and HR (0.09 beats/minute, p < .935). In conclusion, music therapy reduced significantly SBP and HR suggesting that it could be a promising tool to prevent the progression of pre-hypertension toward hypertension among young adults.

Genome-Wide Analysis Revealed Homozygosity and Demographic History of Five Chinese Sheep Breeds Adapted to Different Environments.

Homozygosity of long sequence genotypes are a result of parents transmitting identical haplotypes, which can be used to estimate their auto-zygosity. Therefore, we used high-density SNP Chip data to characterize the auto-zygosity of each breed according to the occurrence and distribution of runs of homozygosity (ROH). Subsequently, we identified the genomic regions with high runs of homozygosity frequencies within individuals of each breed. We selected 96 sheep samples from five local Chinese sheep breeds belonging to different geographical locations. We identified 3046 ROHs within the study breed individuals, among which the longer segments (>1-5 Mb) were dominant. On average, ROH segments covered about 12% of the genomes; the coverage rate of OAR20 was the lowest and that of OAR2 was the highest. The distribution analysis of runs of homozygosity showed that the detected ROH mainly distributed between >26 and 28 Mb. The Hetian and Hu sheep showed the lowest ROH distribution. The estimation of homozygosity level reflects the history of modern and ancient inbreeding, which may affect the genomes of Chinese indigenous sheep breeds and indicate that some animals have experienced recent self-pollination events (Yabuyi, Karakul and Wadi). In these sheep breeds, the genomic regions were assumed to be under selection signatures frequently in line with long ROH. These regions included candidate genes associated with disease resistance traits (5S_rRNA), the innate and adaptive immune response (HERC2 and CYFIP1), digestion and metabolism (CENPJ), growth (SPP1), body size and developments (GJB2 and GJA3). This study highlighted new insights into the ROH patterns and provides a basis for future breeding and conservation strategies of Chinese sheep breeds.

Detecting EEG outliers for BCI on the Riemannian manifold using spectral clustering.

Automatically detecting and removing Electroencephalogram (EEG) outliers is essential to design robust brain-computer interfaces (BCIs). In this paper, we propose a novel outlier detection method that works on the Riemannian manifold of sample covariance matrices (SCMs). Existing outlier detection methods run the risk of erroneously rejecting some samples as outliers, even if there is no outlier, due to the detection being based on a reference matrix and a threshold. To address this limitation, our method, Riemannian Spectral Clustering (RiSC), detects outliers by clustering SCMs into non-outliers and outliers, based on a proposed similarity measure. This considers the Riemannian geometry of the space and magnifies the similarity within the non-outlier cluster and weakens it between non-outlier and outlier clusters, instead of setting a threshold. To assess RiSC performance, we generated artificial EEG datasets contaminated by different outlier strengths and numbers. Comparing Hit-False (HF) difference between RiSC and existing outlier detection methods confirmed that RiSC could detect outliers significantly better (p < 0.001). In particular, RiSC improved HF difference the most for datasets with the most severe outlier contamination.

Expression and In Vivo Characterization of the Antimicrobial Peptide Oncocin and Variants Binding to Ribosomes.

Peptides have important biomedical applications, but poor correlation between in vitro and in vivo activities can limit their development for clinical use. The ability to generate peptides and monitor their expression with new mass spectrometric methods and biological activities in vivo would be an advantage for the discovery and improvement of peptide-based drugs. In this study, a plasmid-based system was used to express the ribosome-targeting peptide oncocin (19 amino acids, VDKPPYLPRPRPPRRIYNR) and to determine its direct antibacterial effects on Escherichia coli. Previous biochemical and structure studies showed that oncocin targets the bacterial ribosome. The oncocin peptide generated in vivo strongly inhibits bacterial growth. In vivo dimethyl sulfate footprinting of oncocin on the rRNA gives results that are consistent with those of in vitro studies but reveals additional binding interactions with E. coli ribosomes. Furthermore, expression of truncated or mutated peptides reveals which amino acids are important for antimicrobial activity. Overall, the in vivo peptide expression system can be used to investigate biological activities and interactions of peptides with their targets within the cellular environment and to separate contributions of the sequence to cellular transport. This strategy has future applications for improving the effectiveness of existing peptides and developing new peptide-based drugs.

Genome-wide association analysis reveals the genetic locus for high reproduction trait in Chinese Arbas Cashmere goat.

BACKGROUND: Litter size is the most important reproductive trait which plays a crucial role in goat production. Therefore, improvement of litter size trait has been of increasing interest in goat industry as small improvement in litter size may lead to large profit. The recent Cashmere goat breeding program produced a high-reproductive genetic line of Arbas Cashmere goat. But the genetic mechanism of high reproduction rate remains largely unknown in this Chinese native goat breed. To address this question, we performed a genome-wide association studies (GWAS) using two groups of goats varying in fecundity. OBJECTIVES: Our study was aimed to investigate the significant SNPs and genes associated with high reproduction trait in Inner Mongolia Arbas Cashmere Goat. METHODS: We used logistic model association to perform GWAS using 47 goats from high fecundity group (~ 190%) and 314 goats from low fecundity group (~ 130%) of the Arbas Cashmere goat breed. RESULTS: We identified 66 genomic regions associated with genome wide significant level wherein six loci were found to be associated with reproduction traits. Further analysis showed that five key candidate genes including KISS1, KHDRBS2, WNT10B, SETDB2 and PPP3CA genes are involved in goat fecundity trait. Gene ontology enrichment analysis revealed that several biological pathways could be involved in the variation of fecundity in female goats. CONCLUSIONS: The identified significant SNPs or genes provide useful information about the underlying genetic control of fecundity trait which will be helpful to use them in goat breeding programs for improving the reproductive efficiency of goats.