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Genome-sequencing studies indicate that all humans carry many genetic variants predicted to cause loss of function (LoF) of protein-coding genes, suggesting unexpected redundancy in the human genome. Here we apply stringent filters to 2951 putative LoF variants obtained from 185 human genomes to determine their true prevalence and properties. We estimate that human genomes typically contain ~100 genuine LoF variants with ~20 genes completely inactivated. We identify rare and likely deleterious LoF alleles, including 26 known and 21 predicted severe disease-causing variants, as well as common LoF variants in nonessential genes. We describe functional and evolutionary differences between LoF-tolerant and recessive disease genes and a method for using these differences to prioritize candidate genes found in clinical sequencing studies.  相似文献   
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White spot syndrome (WSS) is considered as a great threat to commercial farming of the tiger shrimp (Penaeus monodon). The causal agent of WSS is a DNA virus called white spot syndrome virus (WSSV). The prevalence of this dreadful virus infection has been studied in five randomly selected hatcheries located in the Cox’s Bazar district of Bangladesh. Both one-step and nested polymerase chain reaction (PCR) involving two pairs of primers, namely, 146F1/146R1 and 146F2/146R2, amplifying the 1447 bp and 941 bp fragments, respectively, were conducted to detect the WSSV. Out of 60 randomly collected shrimps, 12 (20%) were found to be positive by one-step PCR, while 18 (30%) were found to be positive by nested PCR. The nested PCR was found to be much more sensitive than the one-step PCR. The shrimp specimens showing clinical signs of WSS were positive for WSSV by both one-step and nested PCR. Some of the apparently healthy samples were also found to be positive for WSSV by nested PCR. Among the two primer-pairs, the inner pair amplifying the 941 bp fragment was more sensitive than the outer primer pair amplifying the 1447 bp fragment when used in one-step PCR.  相似文献   
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In this study, four species of penaeid shrimp from Pakistan's inshore waters were studied. These were Penaeus penicillatus (Alcock), Penaeus merguiensis (de Man), Metapenaeus affinis (Milne Edwards) and Parapenaeopsis stylifera (Milne Edwards). During maturation, shrimp ovaries pass through a series of colour changes. The various colours observed in the ovaries of the four species of penaeid shrimps were translucent, white, cream, yellow, green‐yellow, green‐white, light green and dark green. The different type of oocytes observed in histological sections of the penaeid ovaries are as follows: chromatin nucleolar oocytes, perinucleolar oocytes, yolkless oocytes, yolky oocytes and oocytes with cortical bodies. The ovarian developmental stages recognized in these shrimps are: undeveloped, developing, nearly ripe, fully ripe, resorbing and resorbing/ developing. The ovarian developmental stages were similar in all the four species with the exception of the fully ripe stage. In the fully ripe stage of P. penicillatus and P. merguiensis, the cortical bodies were present at the periphery in two shapes; spherical as well as rod‐like. On the other hand, in the fully ripe stage of M. affinis and P. stylifera, the cortical bodies were present only at the periphery and were only spherical. A relationship between colour of ovaries and histological stages of ovarian development was established. A female shrimp with a dark‐green ovary is an indication of the ready‐ to‐spawn condition. In P. merguiensis and Penaeus penicillatus, respectively, 100% and 88.1% females with dark‐green ovaries had oocytes with cortical bodies, whereas in M. affinis and P. stylifera, respectively, 50% and 28.6% females with dark‐green ovaries had oocytes with cortical bodies.  相似文献   
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We aimed to describe the management and productivity of this group of smallholder dairy farmers in Kenya at the beginning of an intervention program and to document relevant observed changes in the 3rd year of the intervention. A 3-year intervention program, focused on management of animal health and nutrition, and milk quality, was implemented by one Kenyan and two Canadian non-governmental organizations (one university based) to help improve the milk production and livelihoods of Kenyan smallholder dairy farmers (primarily women). Thirty farmers were enrolled and completed questionnaires at the start and end of the project. Focus groups were also conducted to obtain qualitative information on livelihood effects from the program. In 2004, 70% of the eligible youngstock (more than 15 months of age) were pregnant, and cows had a long average days-in-milk of 240 days. External parasites, poor hygiene, and long claws were not uncommon among cows, and 37% and 20% of the farms reported clinical intestinal parasitism and diarrhea in youngstock. In 2006, there were significant improvements in the proportion of farms planting high-protein forages, farms using better milking procedures, and on-farm milk storage methods. The reported mastitis incidence rate fell from 0.55 to 0.20 cases/cow-year (p < 0.01), and the average number of cows and youngstock significantly increased from 1.5 and 0.9 to 2.9 and 2.6, respectively. There were reported improvements in the livelihoods among the member families. The partnership-based intervention program significantly improved management and productivity of this group of smallholder dairy farmers in rural Kenya, leading to reported livelihood benefits.  相似文献   
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Septic arthritis is considered a medical emergency. Disease following bacterial colonization can lead to significant morbidity and mortality and requires costly treatment. Antimicrobial properties of regenerative therapies, including mesenchymal stromal cells and platelet products, have been researched extensively in human medicine. Although fewer studies have been conducted in veterinary species, they have shown promising results. The purpose of this study was to evaluate bacterial suppression by equine platelet lysate (EPL) and adipose-derived mesenchymal stromal cells (ASCs) in vitro. We hypothesized that both products would significantly inhibit the growth of Staphylococcus aureus and Escherichia coli. Pooled blood from 10 horses was used for production of EPL. Mesenchymal stromal cells were isolated from adipose tissue harvested from the gluteal region of 3 horses. The study evaluated 3 treatment groups: 10 × EPL, 1.6 million ASCs, and a control, using an incomplete unbalanced block design with repeated measurements. Optical density readings and colony-forming units/mL were calculated at 0, 3, 6, 9, 12, 18, and 24 hours. Decreased bacterial growth was seen at multiple time points for the S. aureus-ASC and S. aureus-EPL treatments, supporting our hypothesis. Increased bacterial growth was noticed in the E. coli-EPL group, with no difference in the E. coli-ASC treatment, which opposed our hypothesis. A clear conclusion of antimicrobial effects of EPL and ASCs cannot be made from this in vitro study. Although it appears that ASCs have a significant effect on decreasing the growth of S. aureus, further studies are needed to explore these effects, particularly in Gram-positive bacteria.  相似文献   
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Some outbreaks involving highly pathogenic avian influenza viruses (HPAIV) of subtypes H5 and H7 were caused by avian-to-human transmissions. In nature, different influenza A viruses can reassort leading to new viruses with new characteristics. We decided to investigate the impact that the NS-segment of H5 HPAIV would have on viral pathogenicity of a classical avian H7 HPAIV in poultry, a natural host. We focussed this study based on our previous work that demonstrated that single reassortment of the NS-segment from an H5 HPAIV into an H7 HPAIV changes the ability of the virus to replicate in mammalian hosts. Our present data show that two different H7-viruses containing an NS-segment from H5–types (FPV NS GD or FPV NS VN) show an overall highly pathogenic phenotype compared with the wild type H7–virus (FPV), as characterized by higher viral shedding and earlier manifestation of clinical signs. Correlating with the latter, higher amounts of IFN-β mRNA were detected in the blood of NS-reassortant infected birds, 48 h post-infection (pi). Although lymphopenia was detected in chickens from all AIV-infected groups, also 48 h pi those animals challenged with NS-reassortant viruses showed an increase of peripheral monocyte/macrophage-like cells expressing high levels of IL-1β, as determined by flow cytometry. Taken together, these findings highlight the importance of the NS-segment in viral pathogenicity which is directly involved in triggering antiviral and pro-inflammatory cytokines found during HPAIV pathogenesis in chickens.  相似文献   
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ABSTRACT: An experimental infection with highly pathogenic avian influenza virus (HPAIV) and low pathogenic avian influenza virus (LPAIV) was carried out in red-legged partridges (Alectoris rufa) in order to study clinical signs, gross and microscopic lesions, and viral distribution in tissues and viral shedding. Birds were infected with a HPAIV subtype H7N1 (A/Chicken/Italy/5093/1999) and a LPAIV subtype H7N9 (A/Anas crecca/Spain/1460/2008). Uninoculated birds were included as contacts in both groups. In HPAIV infected birds, the first clinical signs were observed at 3 dpi, and mortality started at 4 dpi, reaching 100% at 8 dpi. The presence of viral antigen in tissues and viral shedding were confirmed by immunohistochemistry and quantitative real time RT-PCR (qRRT-PCR), respectively, in all birds infected with HPAIV. However, neither clinical signs nor histopathological findings were observed in LPAIV infected partridges. In addition, only short-term viral shedding together with seroconversion was detected in some LPAIV inoculated animals. The present study demonstrates that the red-legged partridge is highly susceptible to the H7N1 HPAIV strain, causing severe disease, mortality and abundant viral shedding and thus contributing to the spread of a potential local outbreak of this virus. In contrast, our results concerning H7N9 LPAIV suggest that the red-legged partridge is not a reservoir species for this virus.  相似文献   
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