Miracle-dz/UniFAR-FTUs huggingface dataset:
MiR‐205 silences MED1 in hypoxic primary human trophoblasts

Acting through degradation of target mRNA or inhibition of translation, microRNAs (miRNAs) regulate development, differentiation, and cellular response to diverse cues. We analyzed changes in miRNA expression in human placental trophoblasts exposed to hypoxia, which may result from hypoperfusion and placental injury. Using an miRNA microarray screen, confirmed by Northern blot analysis, we defined a set of seven miRNAs (miR‐93, miR‐205, miR‐224, miR‐335, miR‐424, miR‐451, and miR‐491) that are differentially regulated in primary trophoblasts exposed to hypoxia. We combined in silico prediction of miRNA targets with gene expression profiling data to identify a series of potential targets for the miRNAs, which were further analyzed using luciferase reporter assays. Among experimentally confirmed targets, we found that the transcriptional coactivator MED1, which plays an important role in placental development, is a target for miR‐205. Using gain‐ and loss‐of‐function assays, we confirmed that miR‐205 interacts with a specific target in the 3′‐UTR sequence of MED1 and silences MED1 expression in human trophoblasts exposed to hypoxia, suggesting that miR‐205 plays a role in trophoblast injury. —Mouillet, J.‐F. , Chu, T. , Nelson, D. M. , Mishima, T. , Sadovsky, Y. MiR‐205 silences MED1 in hypoxic primary human trophoblasts. FASEB J. 24, 2030–2039 (2010). www.fasebj. org
Submission of Rifaximin to Different Techniques: Characterization, Solubility Study, and Microbiological Evaluation

Rifaximin, an oral antimicrobial drug, is marketed as 200-mg tablets. The daily dose ranges from 600 mg (1 tablet 3 times a day) to 800 mg (2 tablets twice a day). It is used for a wide range of ages, from adults to children, since it is indicated for the treatment of hepatic encephalopathy, travelers’ diarrhea, irritable bowel syndrome, Clostridium difficile, ulcerative colitis, and acute diarrhea. The success of pharmacotherapy will depend on correct fulfillment of drug administration; however, it becomes difficult when the tablets are large and the doses are frequent. Rifaximin belongs to class IV according to the Biopharmaceutic Classification System (BCS), meaning that it is both poorly soluble and poorly permeable. Thus, in this study, solubility of rifaximin was improved by its complexation to β-cyclodextrin by (i) phase solubility diagram, (ii) malaxation, and (iii) decreasing particle size by wet milling. Improved solubility provides lower doses and facilitates compliance with pharmacotherapy. The products formed were analyzed by spectrophotometry in the infrared region (FT-IR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Also, their solubility and microbiological activity were determined. The products obtained in all techniques were more soluble than the free drug; they presented higher thermal stability and antimicrobial potency was approximately 100% with all the formulations. It is important to highlight that the treatment failure not only affects the quality of life of the patients, but also contributes significantly to the economic burden of the health system. Therefore, these findings are extremely interesting, both from a technological and financial point of view.
Vegetation diversity on coal mine spoil heaps – how important is the texture of the soil substrate?

The relationship between the size of the particle fractions of the soil substrate and the diversity of the spontaneously developing vegetation was investigated on coal mine spoil heaps in Upper Silesia (Southern Poland). The analyses were based on 2567 research plots of developed spontaneous vegetation and their associated soil substrate samples collected from 112 coal mine spoil heaps. For each research plot the prevailing particle size fraction was determined (stones, gravel, sand, silt), the species composition and abundance was recorded and the species richness (S), Shannon-Wiener diversity index (H′), Simpson (C) and Evenness (E) indices were used to determine species diversity. From a total of 119 research plots (in all particle size fraction categories), the values of 15 physicochemical properties (pH, electrical conductivity, water holding capacity, moisture, carbon content, total N, available P, Mg and exchange cations Ca, Mg, K, Na, fine particles (%), gravel (%), stone (%)) were obtained to asses their impact on the floristic composition of vegetation patches using Canonical Correspondence Analysis (CCA). Additionally, functional traits of the dominant species of each vegetation patch (life forms, life strategies and socio-ecological groups), were selected to analyse their relation to substrate texture. It was shown that the highest species richness and the highest values for Shannon-Wiener diversity index, as well as Simpson and Evenness indices, were obtained in plots formed on stones. Moreover, the greatest variation in the participation of species representing different habitats, life forms, and life strategies was found on gravelly substrates. Contrary to our expectations, the vegetation diversity (in terms of both species and their functional traits) was not highest in habitats with a high composition of fine size particles.
The mRNA interferases, MazF‐mt3 and MazF‐mt7 from Mycobacterium tuberculosis target unique pentad sequences in single‐stranded RNA

mRNA interferases are sequence‐specific endoribonucleases encoded by toxin‐antitoxin (TA) systems in bacterial genomes. Previously, we demonstrated that Mycobacterium tuberculosis contains at least seven genes encoding MazF homologues (MazF‐mt1 to ‐mt7) and determined cleavage specificities for MazF‐mt1 and MazF‐mt6. Here we have developed a new general method for the determination of recognition sequences longer than three bases for mRNA interferases with the use of phage MS2 RNA as a substrate and CspA, an RNA chaperone, which prevents the formation of secondary structures in the RNA substrate. Using this method, we determined that MazF‐mt3 cleaves RNA at UU˘CCU or CU˘CCU and MazF‐mt7 at U˘CGCU (˘indicates the cleavage site). As pentad sequence recognition is more specific than those of previously characterized mRNA interferases, bioinformatics analysis was carried out to identify M. tuberculosis mRNAs that may be resistant to MazF‐mt3 and MazF‐mt7 cleavage. The pentad sequence was found to be significantly underrepresented in several genes, including members of the PE and PPE families, large families of proteins that play a role in tuberculosis immunity and pathogenesis. These data suggest that MazF‐mt3 and MazF‐mt7 or other mRNA interferases that target longer RNA sequences may alter protein expression through differential mRNA degradation, a regulatory mechanism that may allow adaptation to environmental conditions, including those encountered by pathogens such as M. tuberculosis during infection.
Identification of transcriptional activators for thienamycin and cephamycin C biosynthetic genes within the thienamycin gene cluster from Streptomyces cattleya

Two regulatory genes, thnI and thnU, were identified in the thienamycin (thn) gene cluster from Streptomyces cattleya. ThnI resembles LysR‐type transcriptional activators and ThnU belongs to the SARP family of transcriptional activators. Their functional role was established after independent inactivation by gene replacement together with transcriptional analysis involving reverse transcription polymerase chain reaction (RT‐PCR). Deletion of thnI abolished thienamycin production showing its involvement in thienamycin biosynthesis. Gene expression analysis applied to the thn gene cluster demonstrated that ThnI is a transcriptional activator essential for thienamycin biosynthesis that regulates the expression of nine genes involved in thienamycin assembly and export (thnH, thnJ, thnK, thnL, thnM, thnN, thnO, thnP and thnQ). Unexpectedly, the thnU disrupted mutant was not affected in thienamycin production but turned out to be essential for cephamycin C biosynthesis. Transcript analysis applied to early and late structural genes for cephamycin C biosynthesis (pcbAB and cmcI), revealed that ThnU is the transcriptional activator of these cephamycin C genes although they are not physically linked to the thn cluster. In addition, it was shown that deletion of thnI has an upregulatory effect on pcbAB and cmcI transcription consistent with a significant increase in cephamycin C biosynthesis in this mutant.
Unique and redundant functions of integrins in the epidermis

The skin forms a barrier against the environment and protects us from mechanical trauma, pathogens, radiation, dehydration, and dangerous temperature fluctuations. The epithelium of the skin, the epidermis, is in a continuous equilibrium of growth and differentiation and has the remarkable capacity to self‐renew completely, which relies on reservoirs of stem cells. Epidermal homeostasis is further dependent on proper repair after injury, and on tight adhesion to the underlying basement membrane. Epidermal adhesion is mediated primarily by integrins, cell‐surface receptors that connect the extracellular matrix to the cytoskeleton. In addition, numerous in vitro reports have implicated integrins, integrin‐associated proteins, or downstream integrin effectors in the regulation of a plethora of cellular processes other than adhesion. Over the past decade, a wealth of information on the function of these proteins has been gathered both from (conditional) knockout mice and from human skin disorders, allowing for a reconstruction of integrin signaling pathways in vivo. Here, we address how epidermal integrins and integrin‐associated proteins regulate keratinocyte adhesion, proliferation, and differentiation, as well as signal transduction, re‐epithelialization during wound healing, hair growth, and stem cell maintenance. Furthermore, we discuss human pathologies associated with altered integrin functions in the epidermis. —Margadant, C. , Charafeddine, R. A. , Sonnenberg, A. Unique and redundant functions of integrins in the epidermis. FASEB J. 24, 4133–4152 (2010). www.fasebj. org
Stratified Labeling for Surface Consistent Parallax Correction and Occlusion Completion

The light field faithfully records the spatial and angular configurations of the scene, which facilitates a wide range of imaging possibilities. In this work, we propose an LF synthesis algorithm which renders high quality novel LF views far outside the range of angular baselines of the given references. A stratified synthesis strategy is adopted which parses the scene content based on stratified disparity layers and across a varying range of spatial granularities. Such a stratified methodology proves to help preserve scene structures over large perspective shifts, and it provides informative clues for inferring the textures of occluded regions. A generative-adversarial network model is further adopted for parallax correction and occlusion completion conditioned on the stratified synthesis features. Experiments show that our proposed model can provide more reliable novel view synthesis quality at large baseline extension ratios. Over 3dB quality improvement has been achieved against state-of-the-art LF view synthesis algorithms.
Activation mechanism, functional role and shedding of glycosylphosphatidylinositol‐anchored Yps1p at the Saccharomyces cerevisiae cell surface

Yeast cell wall assembly is a highly regulated and dynamic process. A class of cell surface aspartic peptidases anchored by a glycosylphosphatidylinositol (GPI) group, collectively known as yapsins, was proposed to be involved in cell wall construction. The Saccharomyces cerevisiae Yps1p, the prototypal yapsin, is processed internally within a loop region to produce an α/β two‐subunit enzyme. Here we investigated the activation mechanism of GPI‐anchored Yps1p and identified some of its substrates. We report that all activation steps of GPI‐Yps1p take place at the cell surface and are regulated by the environmental pH. GPI‐Yps1p is active in vivo at pH 6.0 and pH 3.0 and functions as a sheddase for a subset of GPI‐anchored enzymes, including itself and the Gas1 glucanosyltransferase. Importantly, while native GPI‐Yps1p weakly suppresses many phenotypes associated with the yeast kex2Δ mutant, loop mutants that interfere with conversion into the two‐subunit enzyme restore the kex2Δ phenotypes to near wild type level. We propose that cleavage of this internal loop region plays an important regulatory function through stimulating its shedding activity. Collectively, our data provide a direct link between the pH regulation of yeast cell wall assembly and the activity of a yapsin.
A General Construction and Encoder Implementation of Polar Codes

Puncturing and shortening are two general ways to obtain an arbitrary code length and code rate for polar codes. When some of the coded bits are punctured or shortened, it is equivalent to a situation in which the underlying channels of polar codes are different. This fact calls for a general polar code construction, which is not yet available. In this article, a general construction of polar codes is studied in two aspects: 1) the theoretical foundation of the general construction and 2) the hardware implementation of general polar codes encoders. In contrast to the original identical and independent binary-input, memoryless, symmetric (BMS) channels, these underlying BMS channels can be different. The proposed general construction of polar codes is based on the existing Tal–Vardy’s procedure. The symmetric property and the degradation relationship are shown to be preserved under the general setting, rendering the possibility of a modification of Tal–Vardy’s procedure. Simulation results clearly show improved error performance with reordering using the proposed new procedures. Also, a novel encoding hardware architecture is proposed, which supports puncturing and shortening modes. Implementation results show the proposed encoder achieves approximately 30% throughput improvement when one quarter of bits are punctured/shortened.
Complement factor H allotype 402H is associated with increased C3b opsonization and phagocytosis of Streptococcus pyogenes

The main virulence factor of group A streptococcus (GAS), M protein, binds plasma complement regulators factor H (FH) and FH‐like protein 1 (FHL‐1) leading to decreased opsonization. The M protein binding site on FH is within domain 7 in which also the age‐related macular degeneration (AMD)‐associated polymorphism Y402H is located. We studied if FH allotypes 402H and 402Y have different binding affinities to GAS. Plasma‐derived FH allotype 402H and its recombinant fragment FH5‐7(402H) showed decreased binding to several GAS strains. Growth of GAS in human blood taken from FH(402H) homozygous individuals was decreased when compared with blood taken from FH(402Y) homozygous individuals. The effect of the allotype 402H can be explained by combining the previous M protein mutagenesis data and the recently published crystal structure of FH6‐8. In conclusion the data indicate that the AMD‐associated allotype 402H leads to diminished binding of FH to GAS and increased opsonophagocytosis of the bacteria in blood. These results suggest that the homozygous presence of the allele 402H could be associated with decreased risk for severe GAS infections offering an explanation for the high frequency of the allele despite its association with visual impairment.
Arginine induces skeletal muscle fiber type conversion by upregulating Akirin2 and AMPK/PGC-1α in mice

We have previously reported that arginine promotes slow myosin heavy chain expression in cell culture via Akirin2 and the AMP-activated protein kinase (AMPK) signaling pathway. Our goal in the present study was to investigate whether arginine has similar functions and molecular mechanisms in vivo. Kunming mice were fed a diet supplemented with arginine and actively immunized with Akirin2. The study lasted for 40 d. Tibialis anterior (TA) muscle was harvested for analysis. We found that Kunming mice supplemented with arginine significantly increased the oxidative fibers expression and decreased the expression of glycolytic fiber. Expressions of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and AMPK were increased in the TA muscle of arginine-treated Kunming mice. We also find that dietary supplementation of arginine increased the succinate dehydrogenase and malate dehydrogenase activities and decreased the lactate dehydrogenase activity. But active immunization against Akirin2 got opposite results. These results indicated that arginine induced muscle fiber transition from type II to type I, which may be mediated by Akirin2 and AMPK//PGC-1α signaling pathway.
Imposing Label-Relational Inductive Bias for Extremely Fine-Grained Entity Typing

Existing entity typing systems usually exploit the type hierarchy provided by knowledge base (KB) schema to model label correlations and thus improve the overall performance. Such techniques, however, are not directly applicable to more open and practical scenarios where the type set is not restricted by KB schema and includes a vast number of free-form types. To model the underlying label correlations without access to manually annotated label structures, we introduce a novel label-relational inductive bias, represented by a graph propagation layer that effectively encodes both global label co-occurrence statistics and word-level similarities. On a large dataset with over 10,000 free-form types, the graph-enhanced model equipped with an attention-based matching module is able to achieve a much higher recall score while maintaining a high-level precision. Specifically, it achieves a 15.3% relative F1 improvement and also less inconsistency in the outputs. We further show that a simple modification of our proposed graph layer can also improve the performance on a conventional and widely-tested dataset that only includes KB-schema types.
Deep Visual MPC-Policy Learning for Navigation

Humans can routinely follow a trajectory defined by a list of images/landmarks. However, traditional robot navigation methods require accurate mapping of the environment, localization, and planning. Moreover, these methods are sensitive to subtle changes in the environment. In this letter, we propose PoliNet, a deep visual model predictive control-policy learning method that can perform visual navigation while avoiding collisions with unseen objects on the navigation path. PoliNet takes in as input a visual trajectory and 360$^{\circ }$ images from robot's current view and outputs velocity commands for a planning horizon of $N$ steps that optimally balance between trajectory following and obstacle avoidance. PoliNet is trained using a differentiable neural image predictive model and a traversability estimation model in an model predictive control setup, with minimal human supervision. PoliNet can be applied to visual trajectory in new scenes without retraining. We show experimentally that the robot can follow a visual trajectory even if it does not start from the exact same position and in the presence of previously unseen obstacles. We validated our algorithm with tests both in a realistic simulation environment and in the real world outperforming state-of-the-art baselines under similar conditions in success rate, coverage rate of the trajectory, and with lower computational load. We also show that we can generate visual trajectory in simulation and execute the corresponding path in the real environment.
RLOC: Neurobiologically Inspired Hierarchical Reinforcement Learning Algorithm for Continuous Control of Nonlinear Dynamical Systems

Nonlinear optimal control problems are often solved with numerical methods that require knowledge of system's dynamics which may be difficult to infer, and that carry a large computational cost associated with iterative calculations. We present a novel neurobiologically inspired hierarchical learning framework, Reinforcement Learning Optimal Control, which operates on two levels of abstraction and utilises a reduced number of controllers to solve nonlinear systems with unknown dynamics in continuous state and action spaces. Our approach is inspired by research at two levels of abstraction: first, at the level of limb coordination human behaviour is explained by linear optimal feedback control theory. Second, in cognitive tasks involving learning symbolic level action selection, humans learn such problems using model-free and model-based reinforcement learning algorithms. We propose that combining these two levels of abstraction leads to a fast global solution of nonlinear control problems using reduced number of controllers. Our framework learns the local task dynamics from naive experience and forms locally optimal infinite horizon Linear Quadratic Regulators which produce continuous low-level control. A top-level reinforcement learner uses the controllers as actions and learns how to best combine them in state space while maximising a long-term reward. A single optimal control objective function drives high-level symbolic learning by providing training signals on desirability of each selected controller. We show that a small number of locally optimal linear controllers are able to solve global nonlinear control problems with unknown dynamics when combined with a reinforcement learner in this hierarchical framework. Our algorithm competes in terms of computational cost and solution quality with sophisticated control algorithms and we illustrate this with solutions to benchmark problems.
Learning Integral Representations of Gaussian Processes

We propose a representation of Gaussian processes (GPs) based on powers of the integral operator defined by a kernel function, we call these stochastic processes integral Gaussian processes (IGPs). Sample paths from IGPs are functions contained within the reproducing kernel Hilbert space (RKHS) defined by the kernel function, in contrast sample paths from the standard GP are not functions within the RKHS. We develop computationally efficient non-parametric regression models based on IGPs. The main innovation in our regression algorithm is the construction of a low dimensional subspace that captures the information most relevant to explaining variation in the response. We use ideas from supervised dimension reduction to compute this subspace. The result of using the construction we propose involves significant improvements in the computational complexity of estimating kernel hyper-parameters as well as reducing the prediction variance.
A shifty stop for a hairy tail

The tail apparatus of the bacteriophage SPP1 is an extraordinary ∼1600‐Å‐long molecular machine. The tail mediates attachment of the virus to the host surface receptor, as well‐as ejection of the viral genome into the host. The distal tip of the tail binds the extracellular ectodomain of the Bacillus subtilis receptor YueB, while the tail tube provides a conduit to funnel the viral genome into the host. This process, which culminates with the ejection of the ∼44 kb of viral DNA across the thick, cell envelope of the Gram‐positive bacterial cell, takes place in a time scale of seconds to minutes and represents a remarkable example of biotransformation. In this issue of Molecular Microbiology, Auzat et al. provide compelling evidence that the two major structural proteins of the SPP1 tail, gp17.1 (∼19.1 kDa) and gp17.1* (∼28 kDa), share a common N‐terminal sequence, and that gp17.1* is generated by a translational frameshift in the gene 17.1. The extra domain fused to gp17.1* is synthesized by a +1 programmed translational frameshift at the end of gene 17.1, which leads to the synthesis of approximately one gp17.1* for every three equivalents of gp17.1. This finding extends our current knowledge of translational frameshifts and provides a framework to understand how Siphoviridae phages like SPP1 have developed long‐tail machines using only two major structural proteins.