587 research outputs found

    The oligopeptide ABC transporter OppA4 negatively regulates the virulence factor OspC production of the Lyme disease pathogen

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    Borrelia burgdorferi sensu lato, the agent of Lyme disease, exists in nature through a complex enzootic life cycle that involves both ticks and mammals. The B. burgdorferi genome encodes five Oligopeptide ABC transporters (Opp) that are predicted to be involve in transport of various nutrients. Previously, it was reported that OppA5 is important for the optimal production of OspC, a major virulence factor of B. burgdorferi. In this study, possible role of another Oligopeptide ABC transporter, OppA4 in ospC expression was investigated by construction of an oppA4 deletion mutant and the complemented strain. Inactivation of oppA4 resulted an increased production of OspC, suggesting that OppA4 has a negative impact on ospC expression. Expression of ospC is controlled by Rrp2-RpoN-RpoS, the central pathway essential for mammal infection. We showed that increased ospC expression in the oppA4 mutant was due to an increased rpoS expression. We then further investigated how OppA4 negatively regulates this pathway. Two regulators, BosR and BadR, are known to positively and negatively, respectively, regulate the Rrp2-RpoN-RpoS pathway. We found that deletion of oppA4 resulted in an increased level of BosR. Previous reports showed that bosR is mainly regulated at the post-transcriptional level by other factors. However, OppA4 appears to negatively regulate bosR expression at the transcriptional level. The finding of OppA4 involved in regulation of the Rrp2-RpoN-RpoS pathway further reinforces the importance of nutritional virulence to the enzootic cycle of B. burgdorferi

    Low-bit Shift Network for End-to-End Spoken Language Understanding

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    Deep neural networks (DNN) have achieved impressive success in multiple domains. Over the years, the accuracy of these models has increased with the proliferation of deeper and more complex architectures. Thus, state-of-the-art solutions are often computationally expensive, which makes them unfit to be deployed on edge computing platforms. In order to mitigate the high computation, memory, and power requirements of inferring convolutional neural networks (CNNs), we propose the use of power-of-two quantization, which quantizes continuous parameters into low-bit power-of-two values. This reduces computational complexity by removing expensive multiplication operations and with the use of low-bit weights. ResNet is adopted as the building block of our solution and the proposed model is evaluated on a spoken language understanding (SLU) task. Experimental results show improved performance for shift neural network architectures, with our low-bit quantization achieving 98.76 \% on the test set which is comparable performance to its full-precision counterpart and state-of-the-art solutions.Comment: Accepted at INTERSPEECH 202

    Integral inequalities of Hermite-Hadamard type via qh q-h integrals

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    The well-known Hermite-Hadamard inequality for convex functions is extensively studied for different kinds of integrals and derivatives. This paper investigates some of its variants for qh q-h -integrals using properties of convex functions. Inequalities for q q -integrals that have been published in recent years can be extracted from the main results of this paper

    LtpA, a CdnL-type CarD regulator, is important for the enzootic cycle of the Lyme disease pathogen

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    Little is known about how Borrelia burgdorferi, the Lyme disease pathogen, adapts and survives in the tick vector. We previously identified a bacterial CarD N-terminal-like (CdnL) protein, LtpA (BB0355), in B. burgdorferi that is preferably expressed at lower temperatures, which is a surrogate condition mimicking the tick portion of the enzootic cycle of B. burgdorferi. CdnL-family proteins, an emerging class of bacterial RNAP-interacting transcription factors, are essential for the viability of Mycobacterium tuberculosis and Myxococcus xanthus. Previous attempts to inactivate ltpA in B. burgdorferi have not been successful. In this study, we report the construction of a ltpA mutant in the infectious strain of B. burgdorferi, strain B31-5A4NP1. Unlike CdnL in M. tuberculosis and M. xanthus, LtpA is dispensable for the viability of B. burgdorferi. However, the ltpA mutant exhibits a reduced growth rate and a cold-sensitive phenotype. We demonstrate that LtpA positively regulates 16S rRNA expression, which contributes to the growth defects in the ltpA mutant. The ltpA mutant remains capable of infecting mice, albeit with delayed infection. Additionally, the ltpA mutant produces markedly reduced spirochetal loads in ticks and was not able to infect mice via tick infection. Overall, LtpA represents a novel regulator in the CdnL family that has an important role in the enzootic cycle of B. burgdorferi

    Simulation and analysis of piezoresistive microcantilever

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    Currently, most piezoresistive microcantilever sensors are configured with a dual-layer design that includes a piezoresistor integrated onto the upper surface of a microcantilever. The dual-layer design effectively enhances sensitivity and the piezoresistance effect. However, integrating the piezoresistor onto the microcantilever in the fabrication process necessitates additional steps, leading to extended manufacturing times and increased production costs. In this paper, the mechanical behavior of a single-layer piezoresistive microcantilever, namely displacement, stress, and strain, is investigated and analyzed using ANSYS Multiphysics. The contributing factors expected to affect the device's performance are its geometrical dimensions, and the materials used. Regarding the device dimensions, the length, thickness, and width of the cantilever were varied. It was found that the performance of the piezoresistive microcantilever can be improved by increasing the length and decreasing the thickness. The displacement of the microcantilevers increased by about 230%, from 75.76µm to 250.12µm, when the length was increased from 225µm to 350µm. The applied force ranged from 2uN to 12uN. Similarly, the stress and strain produced on the microcantilevers also increased by about 60.83% and 57.22%, respectively. From the material point of view, the microcantilever made with silicon always had the highest displacement value compared to silicon nitride, silicon dioxide, and polysilicon. This is due to the Young's modulus value, where materials with lower Young's modulus will have higher displacement and stress

    Diversity and Paleodemography of the Addax (<i>Addax nasomaculatus</i>), a Saharan Antelope on the Verge of Extinction.

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    Since the 19th century, the addax (Addax nasomaculatus) has lost approximately 99% of its former range. Along with its close relatives, the blue antelope (Hippotragus leucophaeus) and the scimitar-horned oryx (Oryx dammah), the addax may be the third large African mammal species to go extinct in the wild in recent times. Despite this, the evolutionary history of this critically endangered species remains virtually unknown. To gain insight into the population history of the addax, we used hybridization capture to generate ten complete mitochondrial genomes from historical samples and assembled a nuclear genome. We found that both mitochondrial and nuclear diversity are low compared to other African bovids. Analysis of mitochondrial genomes revealed a most recent common ancestor ~32 kya (95% CI 11-58 kya) and weak phylogeographic structure, indicating that the addax likely existed as a highly mobile, panmictic population across its Sahelo-Saharan range in the past. PSMC analysis revealed a continuous decline in effective population size since ~2 Ma, with short intermediate increases at ~500 and ~44 kya. Our results suggest that the addax went through a major bottleneck in the Late Pleistocene, remaining at low population size prior to the human disturbances of the last few centuries

    An ER surface retrieval pathway safeguards the import of mitochondrial membrane proteins in yeast

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    The majority of organellar proteins are translated on cytosolic ribosomes and must be sorted correctly to function.Targeting routes have been identified for organelles such as peroxisomes and the endoplasmic reticulum (ER). However, little is known about the initial steps of targeting of mitochondrial proteins. In this study, we used a genome-wide screen in yeast and identified factors critical for the intracellular sorting of themitochondrial innermembrane protein Oxa1.The screen uncovered an unexpected path, termed ER-SURF, for targeting ofmitochondrialmembrane proteins.This pathway retrieves mitochondrial proteins from the ER surface and reroutes them to mitochondria with the aid of the ER-localized chaperone Djp1. Hence, cells use the expanse of the ERsurfaces as a fail-safe tomaximize productive mitochondrial protein targeting

    Childhood body mass index and wheezing disorders: a systematic review and meta-analysis

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    BACKGROUND: It has been claimed that overweight/obesity are associated with childhood asthma and wheezing disorders, although the results of observational studies have remained inconsistent. We conducted a systematic review and meta-analysis to investigate this. METHODS: An online search of published papers linking childhood asthma and wheezing with overweight/obesity up to May 2014 using EMBASE and Medline medical research databases was carried out. Summary odds ratios (OR) were estimated using random-effects models. Sub-group meta-analyses were performed to assess the robustness of risk associations and between-study heterogeneity. RESULTS: A total of 38 studies comprising 1,411,335 participants were included in our meta-analysis. The summary ORs of underweight (85th to <95th percentile), and obesity (≥95th percentile) were 0.85 (95% CI: 0.75 to 0.97; P=0.02), 1.23 (95% CI: 1.17 to 1.29; p<0.001), and 1.46, (95% CI: 1.36 to 1.57, P<0.001) respectively. Heterogeneity was significant and substantial in all three weight categories, and not accounted for by predefined study characteristics. CONCLUSION: Our results suggest that underweight is associated with a reduced risk of childhood asthma, and overweight and obesity are associated with an increased risk of childhood asthma. Although our findings assert that overweight/obesity and childhood asthma are associated, the causal pathway and temporal aspects of this relationship remain unanswered and deserve further epidemiological investigation
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