Three new Alpha1-Antitrypsin deficiency variants help to define a C-Terminal region regulating conformational change and polymerization

Alpha1-antitrypsin (AAT) deficiency is a hereditary disorder associated with reduced AAT plasma levels, predisposing adults to pulmonary emphysema. The most common genetic AAT variants found in patients are the mildly deficient S and the severely deficient Z alleles, but several other pathogenic rare alleles have been reported. While the plasma AAT deficiency is a common trait of the disease, only a few AAT variants, including the prototypic Z AAT and some rare variants, form cytotoxic polymers in the endoplasmic reticulum of hepatocytes and predispose to liver disease. Here we report the identification of three new rare AAT variants associated to reduced plasma levels and characterize their molecular behaviour in cellular models. The variants, called Mpisa (Lys259Ile), Etaurisano (Lys368Glu) and Yorzinuovi (Pro391His), showed reduced secretion compared to control M AAT, and accumulated to different extents in the cells as ordered polymeric structures resembling those formed by the Z variant. Structural analysis of the mutations showed that they may facilitate polymerization both by loosening ‘latch’ interactions constraining the AAT reactive loop and through effects on core packing. In conclusion, the new AAT deficiency variants, besides increasing the risk of lung disease, may predispose to liver disease, particularly if associated with the common Z variant. The new mutations cluster structurally, thus defining a region of the AAT molecule critical for regulating its conformational state

Asynchronous Execution of Python Code on Task Based Runtime Systems

Despite advancements in the areas of parallel and distributed computing, the complexity of programming on High Performance Computing (HPC) resources has deterred many domain experts, especially in the areas of machine learning and artificial intelligence (AI), from utilizing performance benefits of such systems. Researchers and scientists favor high-productivity languages to avoid the inconvenience of programming in low-level languages and costs of acquiring the necessary skills required for programming at this level. In recent years, Python, with the support of linear algebra libraries like NumPy, has gained popularity despite facing limitations which prevent this code from distributed runs. Here we present a solution which maintains both high level programming abstractions as well as parallel and distributed efficiency. Phylanx, is an asynchronous array processing toolkit which transforms Python and NumPy operations into code which can be executed in parallel on HPC resources by mapping Python and NumPy functions and variables into a dependency tree executed by HPX, a general purpose, parallel, task-based runtime system written in C++. Phylanx additionally provides introspection and visualization capabilities for debugging and performance analysis. We have tested the foundations of our approach by comparing our implementation of widely used machine learning algorithms to accepted NumPy standards

Response of Wheat Genotypes to Different Levels of Nitrogen

A field experiment was conducted using six genotypes of wheat (Triticum aestivum L.) for response to different levels of nitrogen (N) use. The experiment was laid out in split plot design with four levels (0, 50, 100 and 150 kg N ha-1) as main plots and six wheat genotypes (BL 3623, BL 3629, BL 3872, NL 1008, NL 1055 and Vijay, a check variety) as sub-plots. Grain yield and other yield components increased linearly in response to N concentrations in both seasons. Only two parameters: days to heading (DOH) and days to maturity (DTM) varied significantly (p ≤ 0.05) among wheat genotypes in both the years. None of the parameters showed interaction effects in both seasons. Vijay showed highest grain yield of 3.12 t ha-1 in 2013 with the application of 100 kg N ha-1, and 3.23 t ha-1 in 2014 with 150 kg N ha-1. Spike length, productive tillers m-2, number of spikes m-2 and test weight were greater with higher N rates. The straw yield of wheat fertilized with 150 kg N ha-1 was the highest in Vijay (4.35 t ha-1) and BL 3872 (4.33 t ha-1), respectively. Vijay with 100 kg N ha-1 produced the highest number of productive tillers m-2 (276.33) in 2013 and 296.00 with the application of 150 kg N ha-1 in 2014

Prevalence of extended spectrum β-lactamase, AmpC β-lactamase and metallo β-lactamase mediated resistance in Escherichia coli from diagnostic and tertiary healthcare centers in south Bangalore, India

Background: The increasing reports on multidrug resistant Escherichia coli has become a potential threat to global health. Here, we present a cross-sectional study to characterize extended spectrum β-lactamase, AmpC β-lactamase and metallo β-lactamase producing E. coli isolated from different human clinical samples.Methods: A total of 300 clinical Gram negative bacterial isolates were collected and re-characterized for the identification of E. coli following standard microbiological techniques. The antimicrobial susceptibility of E. coli isolates was initially screened by Kirby-Bauer disk diffusion and MIC methods. The resistant isolates were confirmed to be ESBL, AmpC and MBL producers by their respective phenotypic confirmatory tests of combined disc method.Results: We identified 203 (68%) E. coli and 97 (32%) Non-E. coli isolates. The highest recovery of E. coli was from urine samples 72 (35%). Combined disc method using ceftazidime/ceftazidime+clavulanic acid and cefotaxime/cefotaxime+clavulanic acid confirmed 156 (79%) and 144 (73%) E. coli as ESBL producers, respectively. Thirty-four (34%) and 16 (27%) resistant E. coli isolates were confirmed to be AmpC and MBL producers, likewise.Conclusions: Increased prevalence of ESBL, AmpC and MBL producing E. coli were observed. Beta-lactamase mediated resistance appears to be prime mechanism in the multidrug resistant E. coli. Thus, early detection of beta lactamase producing E. coli is necessary to avoid treatment failure and prevent the spread of MDR

Understanding Antibiotic Usage on Small-Scale Dairy Farms in the Indian States of Assam and Haryana Using a Mixed-Methods Approach-Outcomes and Challenges

The use and misuse of antibiotics in both humans and animals contributes to the global emergence of antimicrobial resistant (AMR) bacteria, a threat to public health and infection control. Currently, India is the world's leading milk producer but antibiotic usage within the dairy sector is poorly regulated. Little data exists reflecting how antibiotics are used on dairy farms, especially on small-scale dairy farms in India. To address this lack of data, a study was carried out on 491 small-scale dairy farms in two Indian states, Assam and Haryana, using a mixed method approach where farmers were interviewed, farms inspected for the presence of antibiotics and milk samples taken to determine antibiotic usage. Usage of antibiotics on farms appeared low only 10% (95% CI 8-13%) of farmers surveyed confirmed using antibiotics in their dairy herds during the last 12 months. Of the farms surveyed, only 8% (6-11%) had milk samples positive for antibiotic residues, namely from the novobiocin, macrolides, and sulphonamide classes of antibiotics. Of the farmers surveyed, only 2% (0.8-3%) had heard of the term "withdrawal period" and 53% (40-65%) failed to describe the term "antibiotic". While this study clearly highlights a lack of understanding of antibiotics among small-scale dairy farmers, a potential factor in the emergence of AMR bacteria, it also shows that antibiotic usage on these farms is low and that the possible role these farmers play in AMR emergence may be overestimated

Antibiotic use, knowledge, and practices of milk vendors in India's informal dairy value chain

BackgroundMilk vendors play an important role in India's dairy value chain; however, their food safety practices are poorly understood. From a milk safety perspective, vendor behavior is significant because it has the potential to affect both consumer and producer behavior. This study describes the types of milk vendors in two Indian states, in an attempt to investigate vendors' hygienic knowledge and practices toward safety and antimicrobial resistance (AMR). MethodsA cross-sectional study was conducted in the states of Assam and Haryana, India. In selected villages, all the milk vendors identified at the time of visit were interviewed. A questionnaire was used to assess the knowledge and practices on antibiotics, milk safety and hygiene. The milk samples were tested for presence of antibiotic resistant bacteria using antibiotic susceptibility testing. ResultsIn total, 244 milk vendors were interviewed during the survey. Out of these, 146 (59.8%) of the vendors traded raw milk, while 40.2% traded pasteurized milk. Vendors were categorized depending on whom they supplied milk to. Five categories were identified: (a) those who sold at grocery shops; (b) those who sold on roadside (roadside vendors); (c) those who sold from door to door; (d) those who sold to sweet makers/tea stalls, and (e) those who sold from own home/other entity. The level of training among vendors on milk hygiene was non-existent and the knowledge related to antibiotics was low. Most of them [210/244 (86.07%)] agreed that boiled milk is always safer than raw milk but almost half [119 (48.77%)] of them admitted that sometimes they drink milk without boiling it. Most vendors believed that they could identify whether milk is safe or not for consumption just by its appearance and smell. Out of 124 milk samples collected from surveyed milk vendors and tested for the presence of antibiotic-resistant bacteria, 80 (64.52%) were tested positive. ConclusionThis study highlights the low levels of knowledge regarding food safety among milk vendors. It shows the predominance of informal milk vendors in the surveyed states and prevalence of AMR bacteria in milk traded by them. Training may be a beneficial strategy for addressing the issue

Ancient Himalayan wolf (Canis lupus chanco) lineage in Upper Mustang of the Annapurna Conservation Area, Nepal

The taxonomic status of the wolf (Canis lupus) in Nepal’s Trans-Himalaya is poorly understood. Recent genetic studies have revealed the existence of three lineages of wolves in the Indian sub-continent. Of these, the Himalayan wolf, Canis lupus chanco, has been reported to be the most ancient lineage historically distributed within the Nepal Himalaya. These wolves residing in the Trans-Himalayan region have been suggested to be smaller and very different from the European wolf. During October 2011, six fecal samples suspected to have originated from wolves were collected from Upper Mustang in the Annapurna Conservation Area of Nepal. DNA extraction and amplification of the mitochondrial (mt) control region (CR) locus yielded sequences from five out of six samples. One sample matched domestic dog sequences in GenBank, while the remaining four samples were aligned within the monophyletic and ancient Himalayan wolf clade. These four sequences which matched each other, were new and represented a novel Himalayan wolf haplotype. This result confirms that the endangered ancient Himalayan wolf is extant in Nepal. Detailed genomic study covering Nepal’s entire Himalayan landscape is recommended in order to understand their distribution, taxonomy and, genetic relatedness with other wolves potentially sharing the same landscape