MLVA genotyping of Chinese human Brucella melitensis biovar 1, 2 and 3 isolates

<p>Abstract</p> <p>Background</p> <p>Since 1950, <it>Brucella melitensis </it>has been the predominant strain associated with human brucellosis in China. In this study we investigated the genotypic characteristics of <it>B. melitensis </it>isolates from China using a multiple-locus variable-number tandem-repeat analysis (MLVA) and evaluated the utility of MLVA with regards to epidemiological trace-back investigation.</p> <p>Results</p> <p>A total of 105 <it>B. melitensis </it>strains isolated from throughout China were divided into 69 MLVA types using MLVA-16. Nei's genetic diversity indices for the various loci ranged between 0.00 - 0.84. 12 out 16 loci were the low diversity with values < 0.2 and the most discriminatory markers were bruce16 and bruce30 with a diversity index of > 0.75 and containing 8 and 7 alleles, respectively. Many isolates were single-locus or double-locus variants of closely related <it>B. melitensis </it>isolates from different regions, including the north and south of China. Using panel 1, the majority of strains (84/105) were genotype 42 clustering to the 'East Mediterranean' <it>B. melitensis </it>group. Chinese <it>B. melitensis </it>are classified in limited number of closely related genotypes showing variation mainly at the panel 2B loci.</p> <p>Conclusion</p> <p>The MLVA-16 assay can be useful to reveal the predominant genotypes and strain relatedness in endemic or non-endemic regions of brucellosis. However it is not suitable for biovar differentiation of <it>B. melitensis</it>. Genotype 42 is widely distributed throughout China during a long time. Bruce 16 and bruce 30 in panel 2B markers are most useful for typing Chinese isolates.</p

QQS orphan gene regulates carbon and nitrogen partitioning across species via NF-YC interactions

The allocation of carbon and nitrogen resources to the synthesis of plant proteins, carbohydrates, and lipids is complex and under the control of many genes; much remains to be understood about this process. QQS (Qua-Quine Starch; At3g30720), an orphan gene unique to Arabidopsis thaliana, regulates metabolic processes affecting carbon and nitrogen partitioning among proteins and carbohydrates, modulating leaf and seed composition in Arabidopsis and soybean. Here the universality of QQS function in modulating carbon and nitrogen allocation is exemplified by a series of transgenic experiments. We show that ectopic expression of QQS increases soybean protein independent of the genetic background and original protein content of the cultivar. Furthermore, transgenic QQS expression increases the protein content of maize, a C4 species (a species that uses 4-carbon photosynthesis), and rice, a protein-poor agronomic crop, both highly divergent from Arabidopsis. We determine that QQS protein binds to the transcriptional regulator AtNF-YC4 (Arabidopsis nuclear factor Y, subunit C4). Overexpression of AtNF-YC4 in Arabidopsis mimics the QQS-overexpression phenotype, increasing protein and decreasing starch levels. NF-YC, a component of the NF-Y complex, is conserved across eukaryotes. The NF-YC4 homologs of soybean, rice, and maize also bind to QQS, which provides an explanation of how QQS can act in species where it does not occur endogenously. These findings are, to our knowledge, the first insight into the mechanism of action of QQS in modulating carbon and nitrogen allocation across species. They have major implications for the emergence and function of orphan genes, and identify a nontransgenic strategy for modulating protein levels in crop species, a trait of great agronomic significance

Rankitect: Ranking Architecture Search Battling World-class Engineers at Meta Scale

Neural Architecture Search (NAS) has demonstrated its efficacy in computer vision and potential for ranking systems. However, prior work focused on academic problems, which are evaluated at small scale under well-controlled fixed baselines. In industry system, such as ranking system in Meta, it is unclear whether NAS algorithms from the literature can outperform production baselines because of: (1) scale - Meta ranking systems serve billions of users, (2) strong baselines - the baselines are production models optimized by hundreds to thousands of world-class engineers for years since the rise of deep learning, (3) dynamic baselines - engineers may have established new and stronger baselines during NAS search, and (4) efficiency - the search pipeline must yield results quickly in alignment with the productionization life cycle. In this paper, we present Rankitect, a NAS software framework for ranking systems at Meta. Rankitect seeks to build brand new architectures by composing low level building blocks from scratch. Rankitect implements and improves state-of-the-art (SOTA) NAS methods for comprehensive and fair comparison under the same search space, including sampling-based NAS, one-shot NAS, and Differentiable NAS (DNAS). We evaluate Rankitect by comparing to multiple production ranking models at Meta. We find that Rankitect can discover new models from scratch achieving competitive tradeoff between Normalized Entropy loss and FLOPs. When utilizing search space designed by engineers, Rankitect can generate better models than engineers, achieving positive offline evaluation and online A/B test at Meta scale.Comment: Wei Wen and Kuang-Hung Liu contribute equall

The brain is a DJ using neuropeptides as sensory crossfaders

Sensory loss induces cross-modal plasticity, often resulting in altered performance in remaining sensory modalities. Whereas much is known about the macroscopic mechanisms underlying cross-modal plasticity, only scant information exists about its cellular and molecular underpinnings. We found that Caenorhabditis elegans nematodes deprived of a sense of body touch exhibit various changes in behavior, associated with other unimpaired senses. We focused on one such behavioral alteration, enhanced odor sensation, and sought to reveal the neuronal and molecular mechanisms that translate mechanosensory loss into improved olfactory acuity. To this end, we analyzed in mechanosensory mutants food-dependent locomotion patterns that are associated with olfactory responses and found changes that are consistent with enhanced olfaction. The altered locomotion could be reversed in adults by optogenetic stimulation of the touch receptor (mechanosensory) neurons. Furthermore, we revealed that the enhanced odor response is related to a strengthening of inhibitory AWC→AIY synaptic transmission in the olfactory circuit. Consistently, inserting in this circuit an engineered electrical synapse that diminishes AWC inhibition of AIY counteracted the locomotion changes in touch-deficient mutants. We found that this cross-modal signaling between the mechanosensory and olfactory circuits is mediated by neuropeptides, one of which we identified as FLP-20. Our results indicate that under normal function, ongoing touch receptor neuron activation evokes FLP-20 release, suppressing synaptic communication and thus dampening odor sensation. In contrast, in the absence of mechanosensory input, FLP-20 signaling is reduced, synaptic suppression is released, and this enables enhanced olfactory acuity; these changes are long lasting and do not represent ongoing modulation, as revealed by optogenetic experiments. Our work adds to a growing literature on the roles of neuropeptides in cross-modal signaling, by showing how activity-dependent neuropeptide signaling leads to specific cross-modal plastic changes in neural circuit connectivity, enhancing sensory performance.status: publishe

Mapping spatial heterogeneity in gastric cancer microenvironment

Gastric cancer (GC) is difficult to characterize due to its heterogeneity, and the complicated heterogeneity leads to the difficulty of precisely targeted therapy. The spatially heterogeneous composition plays a crucial role in GC onset, progression, treatment efficacy, and drug resistance. In recent years, the technological advancements in spatial omics has shifted our understanding of the tumor microenvironment (TME) from cancer-centered model to a dynamic and variant whole. In this review, we concentrated on the spatial heterogeneity within the primary lesions and between the primary and metastatic lesions of GC through the TME heterogeneity including the tertiary lymphoid structures (TLSs), the uniquely spatial organization. Meanwhile, the immune phenotype based on spatial distribution was also outlined. Furthermore, we recapitulated the clinical treatment in mediating spatial heterogeneity in GC, hoping to provide a systematic view of how spatial information could be integrated into anti-cancer immunity

Impact Response of Aluminium Alloy Foams Under Complex Stress States

Abstract A series of dynamic tests were conducted on a closed-cell aluminum alloy foams in order to determine experimental failure surface under impact loading conditions. Quasi-static tests have also been performed to investigate failure mechanism under different stress paths. Three typical types of deformation modes can be observed, which corresponds to the different failure mechanism. The failure loci of the foam in principal stress plane are explored from quasi-static to dynamic loading conditions. A significant strength enhancement is identified experimentally. The expansion of the failure locus from the quasi-static to the dynamic test is almost isotropic. A modified failure criterion for the metallic foam is proposed to predict failure locus as a function of strain rate. This rate-dependence failure criterion is capable of giving a good description of the biaxial failure stresses over a wide range of the strain rates