Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Key Tissue-Specific, Biological Processes by Integrating Enhancer Information in Maize Gene Regulatory Networks

Enhancers are important regulators of gene expression during numerous crucial processes including tissue differentiation across development. In plants, their recent molecular characterization revealed their capacity to activate the expression of several target genes through the binding of transcription factors. Nevertheless, identifying these target genes at a genome-wide level remains a challenge, in particular in species with large genomes, where enhancers and target genes can be hundreds of kilobases away. Therefore, the contribution of enhancers to regulatory network is still poorly understood in plants. In this study, we investigate the enhancer-driven regulatory network of two maize tissues at different stages: leaves at seedling stage and husks (bracts) at flowering. Using a systems biology approach, we integrate genomic, epigenomic and transcriptomic data to model the regulatory relationship between transcription factors and their potential target genes. We identify regulatory modules specific to husk and V2-IST, and show that they are involved in distinct functions related to the biology of each tissue. We evidence enhancers exhibiting binding sites for two distinct transcription factor families (DOF and AP2/ERF) that drive the tissue-specificity of gene expression in seedling immature leaf and husk. Analysis of the corresponding enhancer sequences reveals that two different transposable element families (TIR transposon Mutator and MITE Pif/Harbinger) have shaped the regulatory network in each tissue, and that MITEs have provided new transcription factor binding sites that are involved in husk tissue-specificity. Significance Enhancers play a major role in regulating tissue-specific gene expression in higher eukaryotes, including angiosperms. While molecular characterization of enhancers has improved over the past years, identifying their target genes at the genome-wide scale remains challenging. Here, we integrate genomic, epigenomic and transcriptomic data to decipher the tissue-specific gene regulatory network controlled by enhancers at two different stages of maize leaf development. Using a systems biology approach, we identify transcription factor families regulating gene tissue-specific expression in husk and seedling leaves, and characterize the enhancers likely to be involved. We show that a large part of maize enhancers is derived from transposable elements, which can provide novel transcription factor binding sites crucial to the regulation of tissue-specific biological functions.
Cryo-EM structure of the SARS-CoV-2 3a ion channel in lipid nanodiscs

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes the coronavirus disease 2019 (COVID-19). SARS-CoV-2 encodes three putative ion channels: E, 8a, and 3a1,2. 3a is expressed in SARS patient tissue and anti-3a antibodies are observed in patient plasma3–6. 3a has been implicated in viral release7, inhibition of autophagy8, inflammasome activation9, and cell death10,11 and its deletion reduces viral titer and morbidity in mice1, raising the possibility that 3a could be an effective vaccine or therapeutic target3,12. Here, we present the first cryo-EM structures of SARS-CoV-2 3a to 2.1 Å resolution and demonstrate 3a forms an ion channel in reconstituted liposomes. The structures in lipid nanodiscs reveal 3a dimers and tetramers adopt a novel fold with a large polar cavity that spans halfway across the membrane and is accessible to the cytosol and the surrounding bilayer through separate water- and lipid-filled openings. Electrophysiology and fluorescent ion imaging experiments show 3a forms Ca2+-permeable non-selective cation channels. We identify point mutations that alter ion permeability and discover polycationic inhibitors of 3a channel activity. We find 3a-like proteins in multiple Alphacoronavirus and Betacoronavirus lineages that infect bats and humans. These data show 3a forms a functional ion channel that may promote COVID-19 pathogenesis and suggest targeting 3a could broadly treat coronavirus diseases.
Cooperation between Mucosal Immunology and Plant Biotechnology: Genetic Modification of Plants

Past Records 1982 Ph.D. (Nogaku-Hakushi), Plant Biochemistry, Nagoya University, Japan 1982 Postdoctoral Fellow of JSPS, School of Agriculture, Nagoya University, Japan 1983 JSPS Postdoctoral Fellow for Research Abroad, Biological Laboratories, Harvard University, USA 1984 Assistant Professor, Radioisotope Research Center, Nagoya University, Japan 1991 Associate Professor, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Japan 1993 Associate Professor (Adjunct), Laboratory of Biological Regulation and Photobiology, National Institute for Basic Biology, Japan (until 1998) 2003 Professor, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Japan
A Survey of medicinal plants in Tabora region, Tanzania

A Survey of medicinal plants was conducted in Tabora Region between December, 1970 and July, 1989. 27 traditional healers from 30 villages in 25 village wards (i.e. about 15% of the Region) were interviewed. Also plants in the field and at the Lushoto herbarium were indentified. A total of 127 plant species belonging to 45 families and 05 genera were identified as medicinal plants used for the treatment of some 66 different human diseases in the region. The family Leguminosae was found to be leading by having 33 different medicinal plant species from 20 genera followed by Euphorbiaceae which had 9 species from 7 genera. Antidotes for snake bites were leading with 32 plant species, followed by stomach-ache and coughs, which had 21 and 14 medicinal plant species, respectively.
Towards a new treatment against polymicrobial infections: high antibacterial activity of lemon IntegroPectin against Pseudomonas aeruginosa and Escherichia coli

Lemon IntegroPectin obtained via hydrodynamic cavitation of waste lemon peel in water only shows high antibacterial activity against two Gram-negative bacteria, Pseudomonas aeruginosa and Escherichia coli. The antibacterial effect against the ubiquitous pathogen P. aeruginosa was evaluated in terms of the minimal bactericidal (MBC) and minimal inhibitory concentration (MIC). Preliminary insight on the antibacterial mechanism of IntegroPectin originates from investigating its inhibitory activity against E. coli. Given the non-cytotoxic nature of citrus IntegroPectin and the ease of its reproducible production in large amounts, the route is open to the industrial development of a new antimicrobial treatment against polymicrobial infections unlikely to develop drug resistance.
Advanced age attenuates the antihyperalgesic effect of morphine and decreases μ-opioid receptor expression and binding in the rat midbrain periaqueductal gray in male and female rats

The present study investigated the impact of advanced age on morphine modulation of persistent inflammatory pain in male and female rats. The impact of age, sex, and pain on μ-opioid receptor (MOR) expression and binding in the ventrolateral PAG (vlPAG) was also examined using immunohistochemistry and receptor autoradiography. Intraplantar administration of Complete Freund’s adjuvant induced comparable levels of edema and hyperalgesia in adult (2-3mos) and aged (16-18mos) male and female rats. Morphine potency was highest in adult males, with a two-fold decrease in morphine EC50 observed in aged versus adult males (10.22mg/kg versus 5.19mg/kg). Adult and aged female rats also exhibited significantly higher EC50 values (10.69 mg/kg and 9.00 mg/kg, respectively) compared to adult males. The upward shift in EC50 from adult to aged males was paralleled by a reduction in vlPAG MOR expression and binding. The observed age-related reductions in morphine potency and vlPAG MOR expression and binding have significant implications in pain management in the aged population.
A hand-off of DNA between archaeal polymerases allows high-fidelity replication to resume at a discrete intermediate three bases past 8-oxoguanine

During DNA replication, the presence of 8-oxoguanine (8-oxoG) lesions in the template strand cause the high-fidelity (HiFi) DNA polymerase (Pol) to stall. An early response to 8-oxoG lesions involves ‘on-the-fly’ translesion synthesis (TLS), in which a specialized TLS Pol is recruited and replaces the stalled HiFi Pol for bypass of the lesion. The length of TLS must be long enough for effective bypass, but it must also be regulated to minimize replication errors by the TLS Pol. The exact position where the TLS Pol ends and the HiFi Pol resumes (i.e. the length of the TLS patch) has not been described. We use steady-state and pre-steady-state kinetic assays to characterize lesion bypass intermediates formed by different archaeal polymerase holoenzyme complexes that include PCNA123 and RFC. After bypass of 8-oxoG by TLS PolY, products accumulate at the template position three base pairs beyond the lesion. PolY is catalytically poor for subsequent extension from this +3 position beyond 8-oxoG, but this inefficiency is overcome by rapid extension of HiFi PolB1. The reciprocation of Pol activities at this intermediate indicates a defined position where TLS Pol extension is limited and where the DNA substrate is handed back to the HiFi Pol after bypass of 8-oxoG.
Genetic, Biochemical, and Functional Characterization of Heme Metabolism in Group A Streptococcus

Heme is vital to a variety of cellular functions in bacteria ranging from energy generation to iron reserve. Group A streptococcus (GAS) is a prevalent bacterial pathogen that is responsible for an array of human diseases ranging from simple, self-limiting, mucosal and skin infections to invasive and systemic manifestations. GAS needs iron for growth and can satisfy this nutritional requirement by scavenging the metal from heme. The pathogen produces powerful hemolysins that facilitate heme release during infection. Heme is captured and relayed through the GAS cell wall and cytoplasmic membrane by dedicated receptors and transporters. To-date, the fate of the acquired heme is unknown in Streptococci. Although heme is nutritionally beneficial for GAS growth, its pro-oxidant and lipophilic nature makes it a liability with damaging effects on cellular components. The conundrum associated with heme use is particularly pertinent to GAS pathophysiology since invasive GAS infections involve massive hemolysis and the generation of unescorted heme in excess. In this dissertation, I aimed to describe the mechanisms that GAS uses for heme catabolism while managing its toxicity. I conducted a biochemical characterization of a new enzyme, HupZ in GAS that degrades heme in vitro. Similar to the heme oxygenase-1 (HO-1), HupZ activity leads to the formation of iron, CO, and a biliverdin-like product. I also investigated the impact of heme on GAS physiology and identified key mediators in the repair and detoxification process. This study demonstrated that heme exposure leads to a general stress response that involves the activation of antioxidant defense pathways to restore redox balance. Further, I studied a 3-gene cluster, pefRCD (porphyrin-regulated efflux RCD), which was activated by environmental heme, and provided support to my hypothesis that the pefRCD gene encodes a heme-sensing regulator (PefR) and heme efflux system (PefCD). I showed that the pef system protects GAS cells from hemeinduced damage to the membrane and DNA by preventing cellular accumulation of heme. In conclusion, this dissertation addresses key knowledge gaps in GAS physiology and provides new insights into heme metabolism of GAS. INDEX WORDS: Heme tolerance, Group A streptococcus, Gram-positive, heme sensing, mutational analysis, heme toxicity, heme tolerance, PefRCD transporter, heme efflux, heme degradation, HupZ protein, UV-vis spectroscopy, iron and CO release. GENETIC, BIOCHEMICAL, AND FUNCTIONAL CHARACTERIZATION OF HEME METABOLISM IN GROUP A STREPTOCOCCUS
Research Note: An Evaluation of Soft and Hard Red Winter Wheat for Nitrogen-Corrected True Metabolizable Energy, Crude Protein, and Amino Acid Content

Abstract One study utilizing 8-wk-old Vantress × Arbor Acres male broilers was conducted to determine the TMEn, crude protein, and amino acid content of five soft and five hard composite red winter wheat cultivars from four farms. Soft cultivars evaluated included Caldwell, Pike, Arthur, Hart, and Delange, and the hard cultivars included Payne, Triumph, Tam 101, Chisholm, and Mustang. Energy availability as judged by TMEn, averaged over cultivar within the soft and hard classification, was similar (P > .10) at 3.30 and 3.32 kcal/g, respectively. Considerable variation existed among cultivars within classification, with Payne exhibiting the highest (3.6 kcal/g) and Delange the lowest (2.9 kcal/g) energy content. Average crude protein concentration was higher (P
Ancient Evolutionary Origin of Intrinsically Disordered Cancer Risk Regions

Cancer is a heterogeneous genetic disease that alters the proper functioning of proteins involved in key regulatory processes such as cell cycle, DNA repair, survival or apoptosis. Mutations often accumulate in hot-spots regions, highlighting critical functional modules within these proteins that need to be altered, amplified or abolished for tumor formation. Recent evidence suggests that these mutational hotspots can not only correspond to globular domains but also to intrinsically disordered regions (IDRs), which play a significant role in a subset of cancer types. IDRs have distinct functional properties that originate from their inherent flexibility. Generally, they correspond to more recent evolutionary inventions and show larger sequence variations across species. In this work we analyzed the evolutionary origin of disordered regions that are specifically targeted in cancer. Surprisingly, the majority of these disordered cancer risk regions showed remarkable conservation with ancient evolutionary origin, stemming from the earliest multicellular animals or even beyond. Nevertheless, we encountered several examples, where the mutated region emerged at a later stage compared to the origin of the gene family. We also showed the cancer risk regions become quickly fixated after their emergence, but evolution continues to tinker with their genes with novel regulatory elements introduced even at the level of humans. Our concise analysis provides a much clearer picture of the emergence of key regulatory elements in proteins and highlights the importance of taking into account the modular organisation of proteins for the analyses of evolutionary origin.
Structure-Function Relationships in Anti-DNA and Anti-Phospholipid Antibodies and their Relevance to the Pathogenesis of Disease

Autoantibodies are pathogenic in systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS). These pathogenic autoantibodies are generally characterized by IgG isotype and high affinity binding to particular antigens. In SLE, antibodies to double-stranded DNA (dsDNA), nucleosomes and alpha-actinin are particularly important. In APS, pathogenic antibodies that cause thrombosis or fetal loss are particularly characterized by binding to anionic phospholipids (PL) and beta-2-glycoprotein I. Sequence analysis of human and murine monoclonal anti-dsDNA and aPL antibodies shows that high affinity for these antigens is associated with the presence of the residues arginine (Arg), asparagine (Asn) and lysine (Lys) in the complementarity determining regions (CDRs) of their heavy and light chains. In vitro expression systems have been used to create variants of the antibodies in which these amino acids have been altered. In general, removal of arginine residues reduces affinity for dsDNA, nucleosomes and anionic PL. Arginines at different positions in the sequence have different effects on binding affinity and effects on binding are not always mirrored by effects on pathogenicity. These studies, together with molecular models of antigen/antibody complexes, help us to understand exactly how pathogenic antibodies interact with antigens. Ultimately, this understanding may aid the design of therapeutic agents to block the pathogenic effects of these antibodies.
Restricted Feeding and Compensatory Growth for Broilers

Abstract Two experiments were undertaken to study the influence of early nutrient restriction on body weight, feed utilization, and abdominal fat for broilers at market age. In the first experiment, males and females restricted in feed intake from 7 to 14 days were significantly lighter at 41 days than the birds fed for ad libitum intake or birds fed the control diet from 7 to 14 days diluted with 15% of alpha floc. No significant difference in abdominal fat was noted between treatments at 41 days of age. In the second experiment, male broilers were either restricted in nutrient intake from 7 to 14 days of age or fed higher levels of dietary protein during the last week on test No significant difference in 42-day body weights was noted between ad libitum- fed birds and birds either restricted in feed intake or fed diluted diets between 7 and 14 days or between ad libitum-fed birds and birds fed higher levels of dietary protein between 36 and 42 days of age. Although absolute abdominal fat weight was significantly lower for birds fed the restricted diet than for birds fed the control diet, this difference only amounted to approximately 5 g per bird. Increasing the level of dietary protein by 2% during the last 7 days of the test significantly reduced abdominal carcass fat. However, on an absolute basis, the reduction in abdominal fat only amounted to 10 g per bird.
Reward-based invigoration of sequential reaching

Seeking reward is a powerful tool for shaping human behaviour. While it has been demonstrated that reward invigorates performance of simple movements, its effect on more complex sequential actions is less clear. In addition, it is unknown why reward-based improvements for discrete actions are transient, i.e. performance gains are lost once reward is removed, but appear long lasting for sequential actions. We show across three experiments that reward invigorates sequential reaching performance. Driven by a reward-based increase in speed, movements also exhibited greater coarticulation, smoothness and a closer alignment to a minimum jerk trajectory. Critically, these performance gains were maintained across multiple days even after the removal of reward. We propose that coarticulation, the blending together of sub-movements into a single continuous action, provides a mechanism by which reward can invigorate sequential performance whilst also increasing efficiency. This change in efficiency appears essential for the retention of reward-based improvements in motor behaviour.
Dissecting Response to Cancer Immunotherapy by Applying Bayesian Network Analysis to Flow Cytometry Data

Cancer immunotherapy, specifically immune checkpoint blockade therapy, has been found to be effective in the treatment of metastatic cancers. However, only a subset of patients with certain cancer types achieve clinical responses. Consequently, elucidating immune system-related pre-treatment biomarkers that are predictive with respect to sustained clinical response is a major research priority. Another research priority is evaluating changes in the immune system before and after treatment in responders and non-responders. Specifically, our group has been studying immune signaling networks as an accurate reflection of the global immune state. Flow cytometry data (FACS, Fluorescence-activated cell sorting) characterizing immune signaling in peripheral blood mononuclear cells (PBMC) from gastroesophageal adenocarcinoma (GEA) patients were used to analyze changes in immune signaling networks in this setting. We developed a novel computational pipeline to perform secondary analyses of FACS data using systems biology / machine learning / information-theoretic techniques and concepts, primarily based on Bayesian network modeling. Application of this novel pipeline resulted in determination of immune markers, combinations / interactions thereof, and corresponding immune cell population types that are associated with clinical responses. Future studies are planned to generalize our analytical approach to different cancer types and corresponding datasets. Author Summary It is difficult to predict whether a cancer patient undergoing immunotherapy treatments will respond. As immunotherapy is expensive and may lead to autoimmune toxicities, patient selection is an important issue. One way to gain deeper insight into the underlying processes is to study changes in immune signaling networks during the treatment course. These networks can be modeled, visualized, and quantified using systems biology / machine learning methods, such as Bayesian networks (BNs). Here, we present a BN-based analytical strategy for devising and comparing immune signaling networks, and apply it to data obtained from patients in a gastrointestinal cancer immunotherapy clinical trial. We identify potentially predictive immune biomarkers, and compare and contrast the resulting network models in different groups of patients, before and after therapy. Our analytical strategy generalizes to different cancers and immunotherapy regimens.
Oviposition-deterring, male-arresting, fruit-marking pheromone in Rhagoletis cerasi [Sweet cherries].

Females of the European cherry fruit fly, Rhagoletis cerasi L. , deposit a pheromone (or a complex of pheromones) immediately after oviposition by dragging their extended ovpositor over the surface of cherries or artificial oviposition devices. The function of this pheromone is the prevention of repeated oviposition in already infested oviposition sites, thus assuring a uniform egg dispersion among available fruits. Apparently it also plays a role in sexual behavior by functioning as a male arrestant. The pheromone is soluble in water and methanol, persisting at least 12 days on the fruit surface under laboratory conditions. Chemotactile but no long-range olfactory mechanisms appear to be involved in its perception by the flies. A simple bioassay and a method to collect pheromone solutions by using artificial oviposition devices is described.
DEGRADATION OF PLANT PATHOGENIC FUNGI BY TRICHODERMA HARZIANUM

Trichoderma harzianum excreted β-1, 3-glucanase and chitinase into the medium when grown on laminarin and chitin, respectively, or on cell walls of the pathogen Sclerotium rolfsii, as sole carbon source. Trichoderma harzianum also showed high activity of both enzymes when grown on homogenized S. rolfsii sclerotia. Glucanase activity increased by 67% when the fungus was grown on a mixture of laminarin and glucose (3:1, v/v). Similarly, high lytic activity was detected in wheat bran culture of the fungus and in soil inoculated with this culture. Protease and lipase activity were detected in the medium when the antagonist attacked mycelium of S. rolfsii.Isolates of T. harzianum were found to differ in the levels of hydrolytic enzymes produced when mycelium of S. rolfsii, Rhizoctonia solani, and Pythium aphanidermatum in soil was attacked. This phenomenon was correlated with the ability of each of the Trichoderma isolates to control the respective soilborne pathogens.
Special Issue: From Natural Polyphenols to Synthetic Bioactive Analogues

In recent years, phenolic compounds from plant sources, commonly referred to as 'plant polyphenols', have been the subject of an impressive number of research studies, to a large extent focused on the healthy properties attributed to diet polyphenols, including antioxidant, anti-inflammatory, antineoplastic, antidiabetic, neuroprotective, and other biological activities [. ].