The forkhead transcription factor Foxj1 controls vertebrate olfactory cilia biogenesis and sensory neuron differentiation

In vertebrates, olfactory receptors localize on multiple cilia elaborated on dendritic knobs of olfactory sensory neurons (OSNs). Although olfactory cilia dysfunction can cause anosmia, how their differentiation is programmed at the transcriptional level has remained largely unexplored. We discovered in zebrafish and mice that Foxj1, a forkhead domain-containing transcription factor traditionally linked with motile cilia biogenesis, is expressed in OSNs and required for olfactory epithelium (OE) formation. In keeping with the immotile nature of olfactory cilia, we observed that ciliary motility genes are repressed in zebrafish, mouse, and human OSNs. Strikingly, we also found that besides ciliogenesis, Foxj1 controls the differentiation of the OSNs themselves by regulating their cell type-specific gene expression, such as that of olfactory marker protein (omp) involved in odor-evoked signal transduction. In line with this, response to bile acids, odors detected by OMP-positive OSNs, was significantly diminished in foxj1 mutant zebrafish. Taken together, our findings establish how the canonical Foxj1-mediated motile ciliogenic transcriptional program has been repurposed for the biogenesis of immotile olfactory cilia, as well as for the development of the OSNs

Big data, ethics, and regulations: Implications for consent in the learning health system

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146311/1/mp12707_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146311/2/mp12707.pd

Prediction of Transcriptional Terminators in Bacillus subtilis and Related Species

In prokaryotes, genes belonging to the same operon are transcribed in a single mRNA molecule. Transcription starts as the RNA polymerase binds to the promoter and continues until it reaches a transcriptional terminator. Some terminators rely on the presence of the Rho protein, whereas others function independently of Rho. Such Rho-independent terminators consist of an inverted repeat followed by a stretch of thymine residues, allowing us to predict their presence directly from the DNA sequence. Unlike in Escherichia coli, the Rho protein is dispensable in Bacillus subtilis, suggesting a limited role for Rho-dependent termination in this organism and possibly in other Firmicutes. We analyzed 463 experimentally known terminating sequences in B. subtilis and found a decision rule to distinguish Rho-independent transcriptional terminators from non-terminating sequences. The decision rule allowed us to find the boundaries of operons in B. subtilis with a sensitivity and specificity of about 94%. Using the same decision rule, we found an average sensitivity of 94% for 57 bacteria belonging to the Firmicutes phylum, and a considerably lower sensitivity for other bacteria. Our analysis shows that Rho-independent termination is dominant for Firmicutes in general, and that the properties of the transcriptional terminators are conserved. Terminator prediction can be used to reliably predict the operon structure in these organisms, even in the absence of experimentally known operons. Genome-wide predictions of Rho-independent terminators for the 57 Firmicutes are available in the Supporting Information section

A review of tennis racket performance parameters

The application of advanced engineering to tennis racket design has influenced the nature of the sport. As a result, the International Tennis Federation has established rules to limit performance, with the aim of protecting the nature of the game. This paper illustrates how changes to the racket affect the player-racket system. The review integrates engineering and biomechanical issues related to tennis racket performance, covering the biomechanical characteristics of tennis strokes, tennis racket performance, the effect of racket parameters on ball rebound and biomechanical interactions. Racket properties influence the rebound of the ball. Ball rebound speed increases with frame stiffness and as string tension decreases. Reducing inter-string contacting forces increases rebound topspin. Historical trends and predictive modelling indicate swingweights of around 0.030–0.035 kg/m2 are best for high ball speed and accuracy. To fully understand the effect of their design changes, engineers should use impact conditions in their experiments, or models, which reflect those of actual tennis strokes. Sports engineers, therefore, benefit from working closely with biomechanists to ensure realistic impact conditions

Is gender encoded in the smile? A computational framework for the analysis of the smile driven dynamic face for gender recognition

YesAutomatic gender classification has become a topic of great interest to the visual computing research community in recent times. This is due to the fact that computer-based automatic gender recognition has multiple applications including, but not limited to, face perception, age, ethnicity, identity analysis, video surveillance and smart human computer interaction. In this paper, we discuss a machine learning approach for efficient identification of gender purely from the dynamics of a person’s smile. Thus, we show that the complex dynamics of a smile on someone’s face bear much relation to the person’s gender. To do this, we first formulate a computational framework that captures the dynamic characteristics of a smile. Our dynamic framework measures changes in the face during a smile using a set of spatial features on the overall face, the area of the mouth, the geometric flow around prominent parts of the face and a set of intrinsic features based on the dynamic geometry of the face. This enables us to extract 210 distinct dynamic smile parameters which form as the contributing features for machine learning. For machine classification, we have utilised both the Support Vector Machine and the k-Nearest Neighbour algorithms. To verify the accuracy of our approach, we have tested our algorithms on two databases, namely the CK+ and the MUG, consisting of a total of 109 subjects. As a result, using the k-NN algorithm, along with tenfold cross validation, for example, we achieve an accurate gender classification rate of over 85%. Hence, through the methodology we present here, we establish proof of the existence of strong indicators of gender dimorphism, purely in the dynamics of a person’s smile

Evaluation of Quantitative EEG by Classification and Regression Trees to Characterize Responders to Antidepressant and Placebo Treatment

The study objective was to evaluate the usefulness of Classification and Regression Trees (CART), to classify clinical responders to antidepressant and placebo treatment, utilizing symptom severity and quantitative EEG (QEEG) data. Patients included 51 adults with unipolar depression who completed treatment trials using either fluoxetine, venlafaxine or placebo. Hamilton Depression Rating Scale (HAM-D) and single electrodes data were recorded at baseline, 2, 7, 14, 28 and 56 days. Patients were classified as medication and placebo responders or non-responders. CART analysis of HAM-D scores showed that patients with HAM-D scores lower than 13 by day 7 were more likely to be treatment responders to fluoxetine or venlafaxine compared to non-responders (p=0.001). Youden’s index γ revealed that CART models using QEEG measures were more accurate than HAM-D-based models. For patients given fluoxetine, patients with a decrease at day 2 in θ cordance at AF2 were classified by CART as treatment responders (p=0.02). For those receiving venlafaxine, CART identified a decrease in δ absolute power at day 7 at the PO2 region as characterizing treatment responders (p=0.01). Using all patients receiving medication, CART identified a decrease in δ absolute power at day 2 in the FP1 region as characteristic of nonresponse to medication (p=0.003). Optimal trees from the QEEG CART analysis primarily utilized cordance values, but also incorporated some δ absolute power values. The results of our study suggest that CART may be a useful method for identifying potential outcome predictors in the treatment of major depression

JIB-04 has broad-spectrum antiviral activity and inhibits SARS-CoV-2 replication and coronavirus pathogenesis

Pathogenic coronaviruses are a major threat to global public health. Here, using a recombinant reporter virus-based compound screening approach, we identified small-molecule inhibitors that potently block the replication of severe acute respiratory syndrome virus 2 (SARS-CoV-2). Among them, JIB-04 inhibited SARS-CoV-2 replication in Vero E6 cells with a 50% effective concentration of 695 nM, with a specificity index of greater than 1,000. JIB-04 showe