Miracle-dz/UniFAR-FTUs huggingface dataset:
Mucus Coat, a Dress Code for Tolerance

Mucus is a determinant of gut immune specification and immune tolerance. [Also see Research Article by Shan et al.] The gastrointestinal tract is home to the highest density of commensal bacteria in the human body and is a primary site of pathogen exposure. Understanding how the immune system recognizes and responds to friend or foe in the gut is central to developing treatments for allergic and inflammatory diseases. Both specialized cells and structural compartmentalization of the gut are key controllers of immune responses. In particular, a mucus layer covers the entire gastrointestinal tract, physically separating the microbiota from host tissue and preventing pathogen invasion (1). On page 447 of this issue, Shan et al. (2) reveal that mucus does more than act as a shield—it also influences the function of intestinal antigen-presenting cells and epithelial cells to sustain the ability of the host to maintain tolerance toward food and commensal antigens.
Mice carrying a humanized Foxp2 knock-in allele show region-specific shifts of striatal Foxp2 expression levels

Genetic and clinical studies of speech and language disorders are providing starting points to unravel underlying neurobiological mechanisms. The gene encoding the transcription factor FOXP2 has been the first example of a gene involved in the development and evolution of this human-specific trait. A number of autosomal-dominant FOXP2 mutations are associated with developmental speech and language deficits indicating that gene dosage plays an important role in the disorder. Comparative genomics studies suggest that two human-specific amino acid substitutions in FOXP2 might have been positively selected during human evolution. A knock-in mouse model carrying these two amino acid changes in the endogenous mouse Foxp2 gene (Foxp2hum/hum) shows profound changes in striatum-dependent behaviour and neurophysiology, supporting a functional role for these changes. However, how this affects Foxp2 expression patterns in different striatal regions and compartments has not been assessed. Here, we characterized Foxp2 protein expression patterns in adult striatal tissue in Foxp2hum/hum mice. Consistent with prior reports in wildtype mice, we find that striatal neurons in Foxp2hum/hum mice and wildtype littermates express Foxp2 in a range from low to high levels. However, we observe a shift towards more cells with higher Foxp2 expression levels in Foxp2hum/hum mice, significantly depending on the striatal region and the compartment. As potential behavioural readout of these shifts in Foxp2 levels across striatal neurons, we employed a morphine sensitization assay. While we did not detect differences in morphine-induced hyperlocomotion during acute treatment, there was an attenuated hyperlocomotion plateau during sensitization in Foxp2hum/hum mice. Taken together, these results suggest that the humanized Foxp2 allele in a mouse background is associated with a shift in striatal Foxp2 protein expression pattern.
Roles of tRNA in cell wall biosynthesis

Recent research into various aspects of bacterial metabolism such as cell wall and antibiotic synthesis, degradation pathways, cellular stress, and amino acid biosynthesis has elucidated roles of aminoacyl‐transfer ribonucleic acid (aa‐tRNA) outside of translation. Although the two enzyme families responsible for cell wall modifications, aminoacyl‐phosphatidylglycerol synthases (aaPGSs) and Fem, were discovered some time ago, they have recently become of intense interest for their roles in the antimicrobial resistance of pathogenic microorganisms. The addition of positively charged amino acids to phosphatidylglycerol (PG) by aaPGSs neutralizes the lipid bilayer making the bacteria less susceptible to positively charged antimicrobial agents. Fem transferases utilize aa‐tRNA to form peptide bridges that link strands of peptidoglycan. These bridges vary among the bacterial species in which they are present and play a role in resistance to antibiotics that target the cell wall. Additionally, the formation of truncated peptides results in shorter peptide bridges and loss of branched linkages which makes bacteria more susceptible to antimicrobials. A greater understanding of the structure and substrate specificity of this diverse enzymatic family is necessary to aid current efforts in designing potential bactericidal agents. These two enzyme families are linked only by the substrate with which they modify the cell wall, aa‐tRNA; their structure, cell wall modification processes and the physiological changes they impart on the bacterium differ greatly. WIREs RNA 2012, 3:247–264. doi: 10.1002/wrna.1108
Genomes from Metagenomics

Metagenomic approaches are rapidly expanding our knowledge of microbial metabolic potential. Evaluation of the functional capacities of microorganisms long relied on laboratory cultivation of individual species. About a decade ago, recovery of draft genomes for a few uncultivated bacteria and archaea from natural communities opened the way for physiological prediction of their environmental roles. Further development of the metagenomics methods used in those early studies now allows the rapid delivery of accurately reconstructed microbial genomes from diverse environmental samples. The resulting knowledge has the potential to revolutionize our understanding of the topology of the tree of life and the metabolic capacities distributed across it. Advances in bioinformatics promise a new era in which comprehensive genetic characterization is sufficiently rapid to find application in diagnostics for medicine, agriculture, forensic science, and biotechnology.
A modified brain storm optimization

Brain storm optimization (BSO) is a new kind of swarm intelligence algorithm inspired by human creative problem solving process. Human being is the most intelligent organism in the world and the brainstorming process popularly used by them has been demonstrated to be a significant and promising way to create great ideas for problem solving. BSO transplants the brainstorming process in human being into optimization algorithm design and gains successes. BSO generally uses the grouping, replacing, and creating operators to produce ideas as many as possible to approach the problem global optimum generation by generation. In this paper, we propose two novel designs to enhance the conventional BSO performance. The first design of the modified BSO (MBSO) is that it uses a simple grouping method (SGM) in the grouping operator instead of the clustering method to reduce the algorithm computational burden. The second design is that MBSO uses a novel idea difference strategy (IDS) in the creating operator instead of the Gaussian random strategy. The IDS not only contains open minded element to avoid the ideas being trapped by local optima, but also can match the search environment to create better new ideas for problem solving. Experiments have been conducted to illustrate the effectiveness and efficiency of the MBSO algorithm. Moreover, the contributions of SGM and IDS are investigated to show how and why MBSO can perform better than BSO.
Preventive Assignment of Regenerator in Translucent Optical Networks

In this paper we propose the APR algorithm to assignment regenerator (RA) in translucent optical networks. The aim of our propose to reduce the blocking probability cause by the degradation made by the establishment of a new light path in the others already established in the network. The APR is compared to other strategy that searches assign the minimal number of regenerator per light path (AMR). For the considered scenarios in this paper, the APR achieved a superior performance than AMR blocking probability terms.
Massively Parallel Single-Cell RNA-Seq for Marker-Free Decomposition of Tissues into Cell Types

Sequencing of RNA from thousands of individual immune cells allows unbiased identification of cellular subtypes. In multicellular organisms, biological function emerges when heterogeneous cell types form complex organs. Nevertheless, dissection of tissues into mixtures of cellular subpopulations is currently challenging. We introduce an automated massively parallel single-cell RNA sequencing (RNA-seq) approach for analyzing in vivo transcriptional states in thousands of single cells. Combined with unsupervised classification algorithms, this facilitates ab initio cell-type characterization of splenic tissues. Modeling single-cell transcriptional states in dendritic cells and additional hematopoietic cell types uncovers rich cell-type heterogeneity and gene-modules activity in steady state and after pathogen activation. Cellular diversity is thereby approached through inference of variable and dynamic pathway activity rather than a fixed preprogrammed cell-type hierarchy. These data demonstrate single-cell RNA-seq as an effective tool for comprehensive cellular decomposition of complex tissues. Introducing MARS-Seq Immune cells are typically differentiated by surface markers; however, this designation is somewhat crude and does not allow for fine distinctions that might be characterized by their RNA transcripts. Jaitin et al. (p. 776) used massively parallel single-cell RNA-sequencing (MARS-Seq) analysis to explore cellular heterogeneity within the immune system by assembling an automated experimental platform that enables RNA profiling of cells sorted from tissues using flow cytometry. More than 1000 cells could be sequenced, and unsupervised clustering analysis of the RNA profiles revealed distinct cellular groupings that corresponded to B cells, macrophages, and dendritic cells. This approach provides the ability to perform a bottom-up characterization of in vivo cell-type landscapes independent of cell markers or prior knowledge.
Rrp6: Integrated roles in nuclear RNA metabolism and transcription termination

The yeast RNA exosome is a eukaryotic ribonuclease complex essential for RNA processing, surveillance, and turnover. It is comprised of a barrel‐shaped core and cap as well as a 3′–5′ ribonuclease known as Dis3 that contains both endo‐ and exonuclease domains. A second exonuclease, Rrp6, is added in the nucleus. Dis3 and Rrp6 have both shared and distinct roles in RNA metabolism, and this review will focus primarily on Rrp6 and the roles of the RNA exosome in the nucleus. The functions of the nuclear exosome are modulated by cofactors and interacting partners specific to each type of substrate. Generally, the cofactor TRAMP (Trf4/5–Air2/1–Mtr4 polyadenylation) complex helps unwind unstable RNAs, RNAs requiring processing such as rRNAs, tRNAs, or snRNAs or improperly processed RNAs and direct it toward the exosome. In yeast, Rrp6 interacts with Nrd1, the cap‐binding complex, and RNA polymerase II to aid in nascent RNA processing, termination, and polyA tail length regulation. Recent studies have shown that proper termination and processing of short, noncoding RNAs by Rrp6 is particularly important for transcription regulation across the genome and has important implications for regulation of diverse processes at the cellular level. Loss of proper Rrp6 and exosome activity may contribute to various pathologies such as autoimmune disease, neurological disorders, and cancer. WIREs RNA 2016, 7:91–104. doi: 10.1002/wrna.1317
SAXS studies of RNA: structures, dynamics, and interactions with partners

Small‐angle X‐ray scattering, SAXS, is a powerful and easily employed experimental technique that provides solution structures of macromolecules. The size and shape parameters derived from SAXS provide global structural information about these molecules in solution and essentially complement data acquired by other biophysical methods. As applied to protein systems, SAXS is a relatively mature technology: sophisticated tools exist to acquire and analyze data, and to create structural models that include dynamically flexible ensembles. Given the expanding appreciation of RNA’s biological roles, there is a need to develop comparable tools to characterize solution structures of RNA, including its interactions with important biological partners. We review the progress toward achieving this goal, focusing on experimental and computational innovations. The use of multiphase modeling, absolute calibration and contrast variation methods, among others, provides new and often unique ways of visualizing this important biological molecule and its essential partners: ions, other RNAs, or proteins. WIREs RNA 2016, 7:512–526. doi: 10.1002/wrna.1349
Extracellular RNA in aging

Since the discovery of extracellular RNA (exRNA) in circulation and other bodily fluids, there has been considerable effort to catalog and assess whether exRNAs can be used as markers for health and disease. A variety of exRNA species have been identified including messenger RNA and noncoding RNA such as microRNA (miRNA), small nucleolar RNA, transfer RNA, and long noncoding RNA. Age‐related changes in exRNA abundance have been observed, and it is likely that some of these transcripts play a role in aging. In this review, we summarize the current state of exRNA profiling in various body fluids and discuss age‐related changes in exRNA abundance that have been identified in humans and other model organisms. miRNAs, in particular, are a major focus of current research and we will highlight and discuss the potential role that specific miRNAs might play in age‐related phenotypes and disease. We will also review challenges facing this emerging field and various strategies that can be used for the validation and future use of exRNAs as markers of aging and age‐related disease. WIREs RNA 2017, 8:e1385. doi: 10.1002/wrna.1385
Origin and Spread of de Novo Genes in Drosophila melanogaster Populations

Novel genes derived from ancestral noncoding sequences are polymorphic among fruit fly strains. Comparative genomic analyses have revealed that genes may arise from ancestrally nongenic sequence. However, the origin and spread of these de novo genes within populations remain obscure. We identified 142 segregating and 106 fixed testis-expressed de novo genes in a population sample of Drosophila melanogaster. These genes appear to derive primarily from ancestral intergenic, unexpressed open reading frames, with natural selection playing a significant role in their spread. These results reveal a heretofore unappreciated dynamism of gene content. Losses and Gains In order to better understand the process by which de novo genes originate, Zhao et al. (p. 769, published online 23 January) examined testis-based gene expression among Drosophila melanogaster strains and identified both fixed and polymorphic de novo genes. The results suggest that spontaneous activation of previously noncoding DNA may be an important factor in generating genetic novelty.
Strong Increase of Tc of Sr2RuO4 Under Both Tensile and Compressive Strain

Strained Superconductor Distorting a material and observing its response can allow insight into its electronic properties. Thin films can be strained by placing them on a substrate with a different lattice constant; bulk samples present more of a challenge. Hicks et al. (p. 283) designed an apparatus to apply both tensile and compressive strain and used it to study the properties of the superconductor Sr2RuO4, which has long been hypothesized to host the unusual p-wave superconductivity. The response of the superconducting transition temperature Tc to the applied strain depended on the direction in which the strain was applied, and did not exhibit a cusp predicted to occur around zero strain. As the technique leaves a surface of the probe open to external probes, it could be adopted for a wide range of methods. An apparatus that can apply both tensile and compressive strain is used to study an unconventional superconductor. A sensitive probe of unconventional order is its response to a symmetry-breaking field. To probe the proposed px ± ipy topological superconducting state of Sr2RuO4, we have constructed an apparatus capable of applying both compressive and tensile strains of up to 0.23%. Strains applied along 〈 100 〉 crystallographic directions yield a strong, strain-symmetric increase in the superconducting transition temperature Tc. 〈 110 〉 strains give a much weaker, mostly antisymmetric response. As well as advancing the understanding of the superconductivity of Sr2RuO4, our technique has potential applicability to a wide range of problems in solid-state physics.
Bioinformatic tools for analysis of CLIP ribonucleoprotein data

Investigating the interactions of RNA‐binding proteins (RBPs) with RNAs is a complex task for molecular and computational biologists. The molecular biology techniques and the computational approaches to understand RBP–RNA (or ribonucleoprotein, RNP) interactions have advanced considerably over the past few years and numerous and diverse software tools have been developed to analyze these data. Accordingly, laboratories interested in RNP biology face the challenge of choosing adequately among the available software tools those that best address the biological problem they are studying. Here, we focus on state‐of‐the‐art molecular biology techniques that employ crosslinking and immunoprecipitation (CLIP) of an RBP to study and map RNP interactions. We review the different software tools and databases available to analyze the most widely used CLIP methods, HITS‐CLIP, PAR‐CLIP, and iCLIP. WIREs RNA 2017, 8:e1404. doi: 10.1002/wrna.1404
A solution to the Arf-Kervaire invariant problem

We gave a series of four lectures, the first by the second author and the rest by the first author. The latter was followed by a 2 hour question and answer session. The problem in question is nearly 50 years old and began with Kervaire’s paper [Ker60] of 1960 in which he defined a Z/2-valued invariant φ(M) on certain manifolds M of dimension 4m + 2. He showed that for m = 2 and M aclosed smooth manifolds, it must vanish. He also constructed a topological 10-manifold M on which it is nontrivial. This was one of the earliest examples of a nonsmoothable manifold. Milnor’s paper on exotic 7-spheres [Mil56] had appeared four years earlier. In their subsequent joint work [KM63] they gave a complete classification of exotic spheres in dimensions ≥ 5 in terms of the stable homotopy groups of spheres, modulo a question about manifolds which they left unanswered: For whichm is there a smooth framed manifold of dimension 4m+2 with nontrivial Kervaire invariant? Such manifolds were known to exist for m = 0, 1 and 3, and Kervaire had shown there are none for m = 2. A pivotal step in answering the question was the following result of Browder [Bro69] published in 1969.
A self organizing map based method for understanding features associated with high aesthetic value evolved abstract images

We show a method that allows the pixel data of a set of images to be analyzed independently of any set of computed features. If the high and low aesthetic value images can be separated in the high dimensional space of pixel intensities then for any given set of features computed from the images, those features relevant to high aesthetic value can be determined and the range of feature values that correlate with high aesthetic appeal can be quantified. The method uses the Self Organizing Map to project raw pixel data of images onto a feature map. The aesthetic class of these images is overlayed on the feature map, yielding a semantic map. Average feature values are visualized in gray-scale heat maps and features relevant to aesthetic value are identified. We call this the Pixel Array Self Organizing Map (PASOM) method. For the set of images analyzed, brightness and texture features were identified as being discriminatory between images of high and low aesthetic value. High aesthetic value images tend to have higher brightness and richer textures. These findings were corroborated by a professional artist/photographer as being consistent with the principles for attaining aesthetic value in visual media. The PASOM method yields a semantic map and a visualization of feature value variation that together make possible a detailed analysis of features associated with the aesthetic value of images.
IMAGING DISK DISTORTION OF BE BINARY SYSTEM δ SCORPII NEAR PERIASTRON

The highly eccentric Be binary system δ Sco reached periastron during early 2011 July, when the distance between the primary and secondary was a few times the size of the primary disk in the H band. This opened a window of opportunity to study how the gaseous disks around Be stars respond to gravitational disturbance. We first refine the binary parameters with the best orbital phase coverage data from the Navy Precision Optical Interferometer. Then we present the first imaging results of the disk after the periastron, based on seven nights of five telescope observations with the MIRC combiner at the CHARA array. We found that the disk was inclined 27. °6 ± 6. °0 from the plane of the sky, had a half-light radius of 0.49 mas (2.2 stellar radii), and consistently contributed 71.4% ± 2.7% of the total flux in the H band from night to night, suggesting no ongoing transfer of material into the disk during the periastron. The new estimation of the periastron passage is UT 2011 July 3 07:00 ± 4:30. Re-analysis of archival VLTI-AMBER interferometry data allowed us to determine the rotation direction of the primary disk, constraining it to be inclined either ∼119° or ∼171° relative to the orbital plane of the binary system. We also detect inner disk asymmetries that could be explained by spot-like emission with a few percent of the disk total flux moving in Keplerian orbits, although we lack sufficient angular resolution to be sure of this interpretation and cannot yet rule out spiral density waves or other more complicated geometries.
Femtosecond Crystallography with Ultrabright Electrons and X-rays: Capturing Chemistry in Action

With the recent advances in ultrabright electron and x-ray sources, it is now possible to extend crystallography to the femtosecond time domain to literally light up atomic motions involved in the primary processes governing structural transitions. This review chronicles the development of brighter and brighter electron and x-ray sources that have enabled atomic resolution to structural dynamics for increasingly complex systems. The primary focus is on achieving sufficient brightness using pump-probe protocols to resolve the far-from-equilibrium motions directing chemical processes that in general lead to irreversible changes in samples. Given the central importance of structural transitions to conceptualizing chemistry, this emerging field has the potential to significantly improve our understanding of chemistry and its connection to driving biological processes.
Delivery of therapeutics to the inner ear: The challenge of the blood-labyrinth barrier

This Review discusses invasive and noninvasive therapeutic delivery methods to the inner ear and challenges presented by the blood-labyrinth barrier. Permanent hearing loss affects more than 5% of the world’s population, yet there are no nondevice therapies that can protect or restore hearing. Delivery of therapeutics to the cochlea and vestibular system of the inner ear is complicated by their inaccessible location. Drug delivery to the inner ear via the vasculature is an attractive noninvasive strategy, yet the blood-labyrinth barrier at the luminal surface of inner ear capillaries restricts entry of most blood-borne compounds into inner ear tissues. Here, we compare the blood-labyrinth barrier to the blood-brain barrier, discuss invasive intratympanic and intracochlear drug delivery methods, and evaluate noninvasive strategies for drug delivery to the inner ear.