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As the newly emerged influenza virus starts its journey to infect the world's human population, the genetic secrets of the 2009 outbreak of swine influenza A(H1N1) are being revealed. In extensive phylogenetic analyses, Garten et al. (p. 197 , published online 22 May) confirm that of the eight elements of the virus, the basic components encoded by the hemagglutinin, nucleoprotein, and nonstructural genes originated in birds and transferred to pigs in 1918. Subsequently, these formed a triple reassortant with the RNA polymerase PB1 that transferred from birds in 1968 to humans and then to pigs in 1998, coupled with RNA polymerases PA and PB2 that transferred from birds to pigs in 1998. The neuraminidase and matrix protein genes that complete the virus came from birds and entered pigs in 1979. The analysis offers insights into drug susceptibility and virulence, as well as raising the possibility of hitherto unknown factors determining host specificity. A significant question is, what is the potential for the H1 component of the current seasonal flu vaccine to act as a booster? Apart from the need for ongoing sequencing to monitor for the emergence of new reassortants, future pig populations need to be closely monitored for emerging influenza viruses. Evolutionary analysis suggests a triple reassortant avian-to-pig origin for the 2009 influenza A(H1N1) outbreak. Since its identification in April 2009, an A(H1N1) virus containing a unique combination of gene segments from both North American and Eurasian swine lineages has continued to circulate in humans. The lack of similarity between the 2009 A(H1N1) virus and its nearest relatives indicates that its gene segments have been circulating undetected for an extended period. Its low genetic diversity suggests that the introduction into humans was a single event or multiple events of similar viruses. Molecular markers predictive of adaptation to humans are not currently present in 2009 A(H1N1) viruses, suggesting that previously unrecognized molecular determinants could be responsible for the transmission among humans. Antigenically the viruses are homogeneous and similar to North American swine A(H1N1) viruses but distinct from seasonal human A(H1N1).

Since its identification in April 2009 an A(H1N1) virus containing a unique combination of gene segments from both North American and Eurasian swine lineages has continued to circulate in humans. The 2009 A(H1N1) virus is distantly related to its nearest relatives, indicating that its gene segments have been circulating undetected for an extended period. Low genetic diversity among the viruses suggests the introduction into humans was a single event or multiple events of similar viruses. Molecular markers predicted for adaptation to humans are not currently present in 2009 A(H1N1) viruses, suggesting previously unrecognized molecular determinants could be responsible for the transmission among humans. Antigenically the viruses are homogeneous and similar to North American swine A(H1N1) viruses but distinct from seasonal human A(H1N1).

In patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer progression-free survival than with chemotherapy alone.

Numerous compounds have shown efficacy in limiting development of pulmonary fibrosis using animal models, yet few of these compounds have replicated these beneficial effects in clinical trials. Given the challenges associated with performing clinical trials in patients with idiopathic pulmonary fibrosis (IPF), it is imperative that preclinical data packages be robust in their analyses and interpretations to have the best chance of selecting promising drug candidates to advance to clinical trials. The American Thoracic Society has convened a group of experts in lung fibrosis to discuss and formalize recommendations for preclinical assessment of antifibrotic compounds. The panel considered three major themes (choice of animal, practical considerations of fibrosis modeling, and fibrotic endpoints for evaluation). Recognizing the need for practical considerations, we have taken a pragmatic approach. The consensus view is that use of the murine intratracheal bleomycin model in animals of both genders, using hydroxyproline measurements for collagen accumulation along with histologic assessments, is the best-characterized animal model available for preclinical testing. Testing of antifibrotic compounds in this model is recommended to occur after the acute inflammatory phase has subsided (generally after Day 7). Robust analyses may also include confirmatory studies in human IPF specimens and validation of results in a second system using in vivo or in vitro approaches. The panel also strongly encourages the publication of negative results to inform the lung fibrosis community. These recommendations are for preclinical therapeutic evaluation only and are not intended to dissuade development of emerging technologies to better understand IPF pathogenesis.

Insect farming is expected to increase in coming years, thus generating high quantities of frass (insect excreta). Frass valorization hinges on basic agronomic research prior to industry upscaling. Here, we investigated soil physiochemical properties, SMAF (Soil Management Assessment Framework) soil health, CO 2 efflux, and bermudagrass [ Cynodon dactylon (L.) Pers.] yield and quality as affected by yellow mealworm ( Tenebrio molitor L.) frass [3400 and 6800 kg ha −1 , low (LF) and high (HF) rates], poultry litter (PL; 3400 kg ha −1 ), and ammonium nitrate (AN; 67 kg N ha −1 ). HF increased soil C, N, P, K, and Mg by 10, 12, 44, 58, and 61%, respectively, compared to AN. Even LF increased soil P, K, and Mg by 37, 31, and 32%, respectively, relative to AN. Compared to PL, HF increased soil N, K, and Mg by 12, 30, and 35%, respectively. After two years, HF increased soil C and N stocks 2- and 3-fold, respectively, relative to AN. Forage yield and quality were similar among amendments, while SMAF and CO 2 were unaffected. Frass substantially improved soil fertility and maintained forage yield, underscoring its biofertilizer value and potential to increase circularity in agroecosystems under the global backdrop of reduced availability of non-renewable fertilizers.

Microglia are resident myeloid cells of the central nervous system integral for neuroprotective and neurodegenerative processes. Here the authors describe a unique TGF-β dependent molecular and functional microglia signature that distinguishes these cells from other immune and glial cells in the periphery and brain. Microglia are myeloid cells of the CNS that participate both in normal CNS function and in disease. We investigated the molecular signature of microglia and identified 239 genes and 8 microRNAs that were uniquely or highly expressed in microglia versus myeloid and other immune cells. Of the 239 genes, 106 were enriched in microglia as compared with astrocytes, oligodendrocytes and neurons. This microglia signature was not observed in microglial lines or in monocytes recruited to the CNS, and was also observed in human microglia. We found that TGF-β was required for the in vitro development of microglia that express the microglial molecular signature characteristic of adult microglia and that microglia were absent in the CNS of TGF-β1–deficient mice. Our results identify a unique microglial signature that is dependent on TGF-β signaling and provide insights into microglial biology and the possibility of targeting microglia for the treatment of CNS disease.

The success of genome-wide association (GWA) studies for the detection of sequence variation affecting complex traits in human has spurred interest in the use of large-scale high-density single nucleotide polymorphism (SNP) genotyping for the identification of quantitative trait loci (QTL) and for marker-assisted selection in model and agricultural species. A cost-effective and efficient approach for the development of a custom genotyping assay interrogating 54,001 SNP loci to support GWA applications in cattle is described. A novel algorithm for achieving a compressed inter-marker interval distribution proved remarkably successful, with median interval of 37 kb and maximum predicted gap of <350 kb. The assay was tested on a panel of 576 animals from 21 cattle breeds and six outgroup species and revealed that from 39,765 to 46,492 SNP are polymorphic within individual breeds (average minor allele frequency (MAF) ranging from 0.24 to 0.27). The assay also identified 79 putative copy number variants in cattle. Utility for GWA was demonstrated by localizing known variation for coat color and the presence/absence of horns to their correct genomic locations. The combination of SNP selection and the novel spacing algorithm allows an efficient approach for the development of high-density genotyping platforms in species having full or even moderate quality draft sequence. Aspects of the approach can be exploited in species which lack an available genome sequence. The BovineSNP50 assay described here is commercially available from Illumina and provides a robust platform for mapping disease genes and QTL in cattle.

Nipah virus, a zoonotic pathogen, can cause debilitating disease and death in humans. Currently, countermeasures are limited, with several in various stages of testing but none yet FDA-approved for human use. Evaluation of countermeasure candidates requires safety testing in humans, as well as efficacy testing against lethal challenge in animal models. Herein, we describe the characterization and comparison of the intraperitoneal and intranasal Syrian golden hamster models for Nipah virus strains Malaysia and Bangladesh. Overall, the intraperitoneal route of exposure resulted in a more consistent lethal outcome, regardless of virus strain. Therefore, the IP model was subsequently used to evaluate the use of Favipiravir as a potential positive control for future studies investigating NiV countermeasures. In contrast to prior reported results regarding Favipiravir in Nipah virus-infected hamsters, Favipiravir was only fifty percent effective at preventing death following lethal challenge, regardless of Nipah virus strain. The data suggest that Favipiravir is only partially protective against Nipah virus in hamsters, and, thus, would likely not be an ideal candidate as a positive control in future efficacy studies.

Neutralization of the omicron variant was assessed in serum samples obtained from persons who had received an mRNA-1273 booster. After the standard two-dose vaccine regimen, these titers were approximately 35 times lower than those against the D614G variant. However, boosters increased omicron neutralization by a factor of 20 — to levels that correlate with clinical resistance to infection.

Soil microorganisms are important for maintaining soil health, decomposing organic matter, and recycling nutrients in pasture systems. However, the impact of long-term conservation pasture management on soil microbial communities remains unclear. Therefore, soil microbiome responses to conservation pasture management is an important component of soil health, especially in the largest agricultural land-use in the US. The aim of this study was to identify soil microbiome community differences following 13-years of pasture management (hayed (no cattle), continuously grazed, rotationally grazed with a fenced, un-grazed and unfertilized buffer strip, and a control (no poultry litter or cattle manure inputs)). Since 2004, all pastures (excluding the control) received annual poultry litter at a rate of 5.6 Mg ha −1 . Soil samples were collected at a 0–15 cm depth from 2016–2017 either pre or post poultry litter applications, and bacterial communities were characterized using Illumina 16S rRNA gene amplicon sequencing. Overall, pasture management influenced soil microbial community structure, and effects were different by year ( P  < 0.05). Soils receiving no poultry litter or cattle manure had the lowest richness (Chao). Continuously grazed systems had greater ( P  < 0.05) soil community richness, which corresponded with greater soil pH and nutrients. Consequently, continuously grazed systems may increase soil diversity, owing to continuous nutrient-rich manure deposition; however, this management strategy may adversely affect aboveground plant communities and water quality. These results suggest conservation pasture management (e.g., rotationally grazed systems) may not improve microbial diversity, albeit, buffer strips were reduced nutrients and bacterial movement as evident by low diversity and fertility in these areas compared to areas with manure or poultry litter inputs. Overall, animal inputs (litter or manure) increased soil microbiome diversity and may be a mechanism for improved soil health.