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04 (95% CI, 37.20-581.19). Using the SROC curve, the AUC was 0.9730 and Q* was 0.9248 (SE = 0.0261). The publication bias was P=0.517 (P>0.05). Conclusions The Xpert MTB/RIF for detecting MTB in gastric aspirates was highly accurate. In addition, we observed that the publication bias in the present study was low. Hence, the Xpert MTB/RIF technology is highly accurate and has the advantage of rapid testing for MTB in clinical samples.Congenital myasthenic syndromes (CMS) are characterised by fatigable muscle weakness resulting from impaired neuromuscular transmission. β2-adrenergic agonists are an effective treatment for DOK7-CMS. DOK7 is a component within the AGRN-LRP4-MUSK-DOK7 signaling pathway that is key for the formation and maintenance of the synaptic structure of the neuromuscular junction. The precise mechanism of action of β2-adrenergic agonists at the neuromuscular junction is not fully understood. In this study we investigated whether β2-adrenergic agonists improve both neurotransmission and structural integrity of the neuromuscular junction in a mouse model of DOK7-CMS. Ex-vivo electrophysiological techniques and microscopy of the neuromuscular junction were used to study the effect of salbutamol, a β2-adrenergic agonist, on synaptic structure and function. DOK7-CMS model mice displayed a severe phenotype with reduced weight gain and perinatal lethality. Salbutamol treatment improved weight gain and survival in DOK7 myasthenic mice. Model animals had fewer active neuromuscular junctions, detectable by endplate recordings, compared to age-matched wildtype littermates. Salbutamol treatment increased the number of detectable neuromuscular junctions during endplate recording. Correspondingly, model mice had fewer acetylcholine receptor-stained neuromuscular junctions detected by fluorescent labelling, but following salbutamol treatment an increased number were detectable. The data demonstrate that salbutamol can prolong survival and increase neuromuscular junction number in a severe model of DOK7-CMS.Cyclin-dependent kinase 2 (CDK2) is a member of the larger cell cycle regulating CDK family of kinases, activated by binding partner cyclins as its name suggests. Despite its canonical role in mitosis, CDK2 knockout mice are viable but sterile, suggesting compensatory mechanisms for loss of CDK2 in mitosis but not meiosis. Here, we review the literature surrounding the role of CDK2 in meiosis, particularly a cyclin-independent role in complex with another activator, Speedy 1 (SPY1). From this evidence, we suggest that CDK2 could be a viable non-hormonal male contraceptive target. Lastly, we review the literature of pertinent CDK2 inhibitors from the preclinical to clinical stages, mostly developed to treat various cancers. To date, there is no potent yet selective CDK2 inhibitor that could be repurposed as a contraceptive without appreciable off-target toxicity. To achieve selectivity for CDK2 over closely related kinases, developing compounds that bind outside the conserved ATP-binding site may be necessary.Background The domestic pig (Sus scrofa) is important both as a food source and as a biomedical model given its similarity in size, anatomy, physiology, metabolism, pathology, and pharmacology to humans. The draft reference genome (Sscrofa10.2) of a purebred Duroc female pig established using older clone-based sequencing methods was incomplete, and unresolved redundancies, short-range order and orientation errors, and associated misassembled genes limited its utility. Results We present 2 annotated highly contiguous chromosome-level genome assemblies created with more recent long-read technologies and a whole-genome shotgun strategy, 1 for the same Duroc female (Sscrofa11.1) and 1 for an outbred, composite-breed male (USMARCv1.0). Both assemblies are of substantially higher (>90-fold) continuity and accuracy than Sscrofa10.2. Conclusions These highly contiguous assemblies plus annotation of a further 11 short-read assemblies provide an unprecedented view of the genetic make-up of this important agricultural and biomedical model species. We propose that the improved Duroc assembly (Sscrofa11.1) become the reference genome for genomic research in pigs.Background Diseases are complex phenotypes often arising as an emergent property of a non-linear network of genetic and epigenetic interactions. To translate this resulting state into a causal relationship with a subset of regulatory features, many experiments deploy an array of laboratory assays from multiple modalities. Often, each of these resulting datasets is large, heterogeneous, and noisy. Thus, it is non-trivial to unify these complex datasets into an interpretable phenotype. Although recent methods address this problem with varying degrees of success, they are constrained by their scopes or limitations. Therefore, an important gap in the field is the lack of a universal data harmonizer with the capability to arbitrarily integrate multi-modal datasets. Results In this review, we perform a critical analysis of methods with the explicit aim of harmonizing data, as opposed to case-specific integration. This revealed that matrix factorization, latent variable analysis, and deep learning are potent strategies. Finally, we describe the properties of an ideal universal data harmonization framework. Conclusions A sufficiently advanced universal harmonizer has major medical implications, such as (i) identifying dysregulated biological pathways responsible for a disease is a powerful diagnostic tool; (2) investigating these pathways further allows the biological community to better understand a disease’s mechanisms; and (3) precision medicine also benefits from developments in this area, particularly in the context of the growing field of selective epigenome editing, which can suppress or induce a desired phenotype.Rcd4 is a poorly characterized Drosophila centriole component whose mammalian counterpart, PPP1R35, is suggested to function in centriole elongation and conversion to centrosomes. Here, we show that rcd4 mutants exhibit fewer centrioles, aberrant mitoses, and reduced basal bodies in sensory organs. Rcd4 interacts with the C-terminal part of Ana3, which loads onto the procentriole during interphase, ahead of Rcd4 and before mitosis. Accordingly, depletion of Ana3 prevents Rcd4 recruitment but not vice versa. We find that neither Ana3 nor Rcd4 participates directly in the mitotic conversion of centrioles to centrosomes, but both are required to load Ana1, which is essential for such conversion. Whereas ana3 mutants are male sterile, reflecting a requirement for Ana3 for centriole development in the male germ line, rcd4 mutants are fertile and have male germ line centrioles of normal length. Thus, Rcd4 is essential in somatic cells but is not absolutely required in spermatogenesis, indicating tissue-specific roles in centriole and basal body formation.Both exogenous and endogenous covert spatial attention enhance contrast sensitivity, a fundamental measure of visual function that depends substantially on the spatial frequency and eccentricity of a stimulus. Whether and how each type of attention systematically improves contrast sensitivity across spatial frequency and eccentricity are fundamental to our understanding of visual perception. Previous studies have assessed the effects of spatial attention at individual spatial frequencies and, separately, at different eccentricities, but this is the first study to do so parametrically with the same task and observers. Using an orientation discrimination task, we investigated the effect of attention on contrast sensitivity over a wide range of spatial frequencies and eccentricities. Targets were presented alone or among distractors to assess signal enhancement and distractor suppression mechanisms of spatial attention. At each eccentricity, we found that exogenous attention preferentially enhanced spatial frequencies higher than the peak frequency in the baseline condition. In contrast, endogenous attention similarly enhanced a broad range of lower and higher spatial frequencies. The presence or absence of distractors did not alter the pattern of enhancement by each type of attention. Our findings reveal how the two types of covert spatial attention differentially shape how we perceive basic visual dimensions across the visual field.The human fovea lies at the center of the retina and supports high-acuity vision. In normal visual system development, the highest acuity is correlated with both a high density of cone photoreceptors in the fovea and a magnified retinotopic representation of the fovea in the visual cortex. Both cone density and the cortical area dedicated to each degree of visual space-the latter describing cortical magnification (CM)-steadily decrease with increasing eccentricity from the fovea. In albinism, peak cone density at the fovea and visual acuity are decreased, but seem to be within normal limits in the periphery, thus providing a model to explore the correlation between retinal structure, cortical structure, and behavior. Here, we used adaptive optics scanning light ophthalmoscopy to assess retinal cone density and functional magnetic resonance imaging to measure CM in the primary visual cortex of normal controls and individuals with albinism. We find that retinotopic organization is more varied among individuals with albinism than previously appreciated. Additionally, CM outside the fovea is similar to that in controls, but also more variable. CM in albinism and controls exceeds that which might be predicted based on cone density alone, but is more accurately predicted by retinal ganglion cell density. This finding suggests that decreased foveal cone density in albinism may be partially counteracted by nonuniform connectivity between cones and their downstream signaling partners. Together, these results emphasize that central as well as retinal factors must be included to provide a complete picture of aberrant structure and function in albinism.People routinely perform multiple visual judgments in the real world, yet, intermixing tasks or task variants during training can damage or even prevent learning. This paper explores why. We challenged theories of visual perceptual learning focused on plastic retuning of low-level retinotopic cortical representations by placing different task variants in different retinal locations, and tested theories of perceptual learning through reweighting (changes in readout) by varying task similarity. Discriminating different (but equivalent) and similar orientations in separate retinal locations interfered with learning, whereas training either with identical orientations or sufficiently different ones in different locations released rapid learning. This location crosstalk during learning renders it unlikely that the primary substrate of learning is retuning in early retinotopic visual areas; instead, learning likely involves reweighting from location-independent representations to a decision. We developed an Integrated Reweighting Theory (IRT), which has both V1-like location-specific representations and higher level (V4/IT or higher) location-invariant representations, and learns via reweighting the readout to decision, to predict the order of learning rates in different conditions. RNA Synthesis inhibitor This model with suitable parameters successfully fit the behavioral data, as well as some microstructure of learning performance in a new trial-by-trial analysis.