Miracle-dz/UniFAR-FTUs huggingface dataset:
Predicting biomass of rice with intermediate traits: Modeling method combining crop growth models and genomic prediction models

Genomic prediction (GP) is expected to become a powerful technology for accelerating the genetic improvement of complex crop traits. Several GP models have been proposed to enhance their applications in plant breeding, including environmental effects and genotype-by-environment interactions (G×E). In this study, we proposed a two-step model for plant biomass prediction wherein environmental information and growth-related traits were considered. First, the growth-related traits were predicted by GP. Second, the biomass was predicted from the GP-predicted values and environmental data using machine learning or crop growth modeling. We applied the model to a 2-year-old field trial dataset of recombinant inbred lines of japonica rice and evaluated the prediction accuracy with training and testing data by cross-validation performed over two years. Therefore, the proposed model achieved an equivalent or a higher correlation between the observed and predicted values (0.53 and 0.65 for each year, respectively) than the model in which biomass was directly predicted by GP (0.40 and 0.65 for each year, respectively). This result indicated that including growth-related traits enhanced accuracy of biomass prediction. Our findings are expected to contribute to the spread of the use of GP in crop breeding by enabling more precise prediction of environmental effects on crop traits.
The guanine nucleotide exchange factor VAV3 participates in ERBB4-mediated cancer cell migration

ERBB4 is a member of the epidermal growth factor receptor (EGFR)/ERBB subfamily of receptor tyrosine kinases that regulates cellular processes including proliferation, migration, and survival. ERBB4 signaling is involved in embryogenesis and homeostasis of healthy adult tissues, but also in human pathologies such as cancer, neurological disorders, and cardiovascular diseases. Here, an MS-based analysis revealed the Vav guanine nucleotide exchange factor 3 (VAV3), an activator of Rho family GTPases, as a critical ERBB4-interacting protein in breast cancer cells. We confirmed the ERBB4–VAV3 interaction by targeted MS and coimmunoprecipitation experiments and further defined it by demonstrating that kinase activity and Tyr-1022 and Tyr-1162 of ERBB4, as well as the intact phosphotyrosine-interacting SH2 domain of VAV3, are necessary for this interaction. We found that ERBB4 stimulates tyrosine phosphorylation of the VAV3 activation domain, known to be required for guanine nucleotide exchange factor (GEF) activity of VAV proteins. In addition to VAV3, the other members of the VAV family, VAV1 and VAV2, also coprecipitated with ERBB4. Analyses of the effects of overexpression of dominant-negative VAV3 constructs or shRNA-mediated down-regulation of VAV3 expression in breast cancer cells indicated that active VAV3 is involved in ERBB4-stimulated cell migration. These results define the VAV GEFs as effectors of ERBB4 activity in a signaling pathway relevant for cancer cell migration.
Enhancement of Antigen-specific Antibody and $CD8^+$ T Cell Responses by Codelivery of IL-12-encapsulated Microspheres in Protein and Peptide Vaccination

Background: Although IL-12 has been widely accepted to play a central role in the control of pathogen infection, the use of recombinant IL-12 (rIL-12) as a vaccine adjuvant has been known to be ineffective because of its rapid clearance in the body. Methods: To investigate the effect of sustained release of IL-12 in vivo in the peptide and protein vaccination models, rIL-12 was encapsulated into poly (DL-lactic-co-glycolic acid) (PLGA). Results: We found that codelivery of IL-12-encapsulated microspheres (IL-12EM) could dramatically increase not only antibody responses, but also antigen-specific CD4 + and CD8 + T cell responses. Enhanced immune responses were shown to be correlated with protective immunity against influenza and respiratory syncytial virus (RSV) virus challenge. Interestingly, the enhancement of CD8 + T cell response was not detectable when CD4 + T cell knockout mice were subjected to vaccination, indicating that the enhancement of the CD8 + T cell response by IL-12EM is dependent on CD4 + T cell “help”. Conclusion: Thus, IL-12EM could be applied as an adjuvant of protein and peptide vaccines to enhance protective immunity against virus infection. (Immune Network 2007;7(4): 186-196)
Differential regulation of ACC synthase genes in cold‐dependent and ‐independent ripening in pear fruit

Late pear cultivars such as Passe-Crassane (PC) require a long chilling treatment before they are capable of ripening. Early cultivars such as Old-Home (OH) have no cold prerequisite. The regulation of 1-aminocyclopropane-1-carboxylic acid synthase (ACS) genes was studied in OH, PC and in OH x PC hybrids in order to determine the role of this gene family in the cold requirement. Of the seven Pc-ACS cDNAs isolated, four (Pc-ACSla/b and Pc-ACS2a/b) showed differential expression associated with the cold requirement. Pc-ACS1a transcripts accumulated throughout the cold treatment and, with Pc-ACS2a, during ripening of cold-dependent cultivars. Pc-ACS1b and Pc-ACS2b were detected only during ripening of cold-independent genotypes. Furthermore, Pc-ACS2a transcript accumulation was negatively regulated by ethylene, whereas Pc-ACS2b was positively regulated by the hormone. Pc-ACS3, 4 and 5 transcript accumulation was similar in all genotypes. Genetic analyses of OH, PC, and 22 OH x PC progenies demonstrated that late, cold-dependent cultivars were homozygous for Pc-ACS1a and 2a whereas early, cold-independent cultivars were heterozygous for Pc-ACS1(a/b) and homozygous for Pc-ACS2b. A model is presented in which differences in Pc-ACS alleles and gene expression between cold- and non-cold-requiring pears are critical in determining the ripening behaviour of the cultivars.
Tree Species Composition Predicts Epiphytic Lichen Communities in an African Montane Rain Forest

The ecology of many tropical rain forest organisms, not the least in Africa, remains poorly understood. Here, we present a detailed ecological study of epiphytic lichens in the equatorial montane rain forest of Bwindi National Park (331 km2), Uganda. We evaluated all major lichen growth forms, including selected groups of crustose lichens. In 14 transects at elevations of 1290 m to 2500 m, we sampled 276 trees belonging to 60 species. We recorded all lichen species on each tree trunk between ground level and 2 m above the ground, yielding 191 lichen species in 67 genera, with a mean of 4.7 species per tree. We used non‐metric multi‐dimensional scaling to separate epiphytic lichen assemblages according to tree species composition and elevation. Structural equation modeling indicated that elevation influenced tree species composition and that tree species composition largely determined lichen species composition. Thus, elevation acted indirectly on the lichen assemblages. Further studies examining factors such as bark properties and lichen colonization ecology may clarify what determines the association between tree species and lichen assemblages. The link between lichen assemblages and large‐scale elevation patterns, as well as disturbance and regrowth histories, warrants further study. An analysis of lichen species composition on individual tree species that occur over large elevation ranges would distinguish the effect of tree species on lichen assemblages from the effect of elevation and thus climate. Our study highlights the limited extent of our knowledge of tropical epiphytic lichens.
Macromolecular Crowding Enhances the Detection of DNA and Proteins by a Solid-State Nanopore

Nanopore analysis of nucleic acid is now routine, but detection of proteins remains challenging. Here, we report the systematic characterization of the effect of macromolecular crowding on the detection sensitivity of a solid-state nanopore for circular and linearized DNA plasmids, globular proteins (β-galactosidase), and filamentous proteins (α-synuclein amyloid fibrils). We observe a remarkable ca. 1000-fold increase in the molecule count for the globular protein β-galactosidase and a 6-fold increase in peak amplitude for plasmid DNA under crowded conditions. We also demonstrate that macromolecular crowding facilitates the study of the topology of DNA plasmids and the characterization of amyloid fibril preparations with different length distributions. A remarkable feature of this method is its ease of use; it simply requires the addition of a macromolecular crowding agent to the electrolyte. We therefore envision that macromolecular crowding can be applied to many applications in the analysis of biomolecules by solid-state nanopores.
Abnormally short serum half‐lives of IgG in β2‐microglobulin‐deficient mice

The MHC class I‐related receptor, FcRn, mediates the transfer of maternal gamma globulin (IgG) to young rodents, primarily via intestinal transcytosis, and this provides humoral immunity for the first few weeks after birth. In a previous study, the site of mouse IgG1 (mIgG1) with which FcRn interacts has been mapped using recombinant wild‐type and mutated Fc‐hinge fragments. The site encompasses residues at the CH2‐CH3 domain interface of Fc (Ile253, His310, Gln311, His433 and Asn434) and the same amino acids are involved in regulating the pharmacokinetics of the Fc‐hinge fragments. This suggests that in addition to its known function, FcRn might also play a role in IgG homeostasis. Consistent with this hypothesis, in this study, we demonstrate that FcRn α‐chain mRNA is present not only in neonatal brush border but also in other tissues of adult animals (liver, lung, spleen and endothelial cells). In addition, analysis of the pharmacokinetics of mouse Ig/Fc‐hinge fragments in genetically manipulated mice that are deficient in the expression of FcRn demonstrates that the β‐phase half‐lives are abnormally short. These findings suggest that FcRn is involved in IgG homeostasis.
Pomegranate Mesocarp against Colitis-Induced Visceral Pain in Rats: Effects of a Decoction and Its Fractions

The management of chronic visceral pain related to Inflammatory Bowel Diseases or Irritable Bowel Syndrome is still a clinical problem and new therapeutic strategies continue to be investigated. In the present study, the efficacy of a pomegranate decoction and of its polysaccharide and ellagitannin components in preventing the development of colitis-induced abdominal pain in rats was evaluated. After colitis induction by 2,4-dinitrobenzenesulfonic acid (DNBS), the pomegranate decoction (300 mg kg−1), polysaccharides (300 mg kg−1), and ellagitannins (45 mg kg−1) were orally administered for 14 days. Repeated treatment with decoction reduced visceral hypersensitivity in the colitic animals both at 7 and 14 days. Similar efficacy was shown by polysaccharides, but with lower potency. Ellagitannins administered at dose equivalent to decoction content showed higher efficacy in reducing the development of visceral pain. Macroscopic and microscopic evaluations performed on the colon 14 days after the damage showed that all three preparations reduced the overall amount of mast cells, the number of degranulated mast cells, and the density of collagen fibers in the mucosal stroma. Although ellagitannins seem to be responsible for most of the beneficial effects of pomegranate on DNBS-induced colitis, the polysaccharides support and enhance its effect. Therefore, pomegranate mesocarp preparations could represent a complementary approach to conventional therapies for promoting abdominal pain relief.
Zn2+-induced changes in Cav2.3 channel function: An electrophysiological and modeling study

Neumaier et al. reveal that Zn2+ effects on Cav2.3 channels are complex, can be either inhibitory or stimulatory, and may persist for several minutes after cessation of the Zn2+ signal. A Markov model is developed that can account for Cav2.3 channel currents in the absence and presence of physiological Zn2+ concentrations.
The AMP-Activated Protein Kinase Plays a Role in Antioxidant Defense and Regulation of Vascular Inflammation

Cardiovascular diseases represent the leading cause of global deaths and life years spent with a severe disability. Endothelial dysfunction and vascular oxidative stress are early precursors of atherosclerotic processes in the vascular wall, all of which are hallmarks in the development of cardiovascular diseases and predictors of future cardiovascular events. There is growing evidence that inflammatory processes represent a major trigger for endothelial dysfunction, vascular oxidative stress and atherosclerosis and clinical data identified inflammation as a cardiovascular risk factor on its own. AMP-activated protein kinase (AMPK) is a central enzyme of cellular energy balance and metabolism that has been shown to confer cardio-protection and antioxidant defense which thereby contributes to vascular health. Interestingly, AMPK is also redox-regulated itself. We have previously shown that AMPK largely contributes to a healthy endothelium, confers potent antioxidant effects and prevents arterial hypertension. Recently, we provided deep mechanistic insights into the role of AMPK in cardiovascular protection and redox homeostasis by studies on arterial hypertension in endothelial and myelomonocytic cell-specific AMPK knockout (Cadh5CrexAMPKfl/fl and LysMCrexAMPKfl/fl) mice. Using these cell-specific knockout mice, we revealed the potent anti-inflammatory properties of AMPK representing the molecular basis of the antihypertensive effects of AMPK. Here, we discuss our own findings in the context of literature data with respect to the anti-inflammatory and antioxidant effects of AMPK in the specific setting of arterial hypertension as well as cardiovascular diseases in general.
Use of three artificial sea salts to maintain fertile sea urchins (arbacia punctulata) and to conduct fertilization tests with copper and sodium dodecyl sulfate

Fertile sea urchins were maintained over six months in three commercial artificial sea-waters (Forty Fathoms®, HW Marinemix®, and Instant Ocean®). Fertilization tests using the reference toxicants copper (Cu) and sodium dodecyl sulfate (SDS) were conducted with the sea urchins in the artificial sea salt in which the organisms were maintained. The ranges of Cu and SDS no-observed-effect concentrations (NOECs) for the tests in the three artificial seawaters overlapped one another and also the ranges of published results for animals maintained and tested in natural sea-water. The 50% effect concentration (EC50) values of Cu for the tests using the three artificial sea-waters were not significantly different. The EC50 value for SDS using HW Marinemix was significantly lower than values for tests using the other artificial seawaters. The artificial seawaters were judged acceptable for maintaining Arbacia punctulata and conducting fertilization tests, although additional research is required to optimize long-term maintenance of fertile animals.
Cytochrome and alternative pathway activity in roots of thermal and non-thermal Agrostis species in response to high soil temperature

Partitioning of respiration between the cytochrome pathway (CP) and the alternative pathway (AP) may play an important role in plant adaptation to extreme environments. We examined changes in partitioning between CP and AP, and viability of roots associated with plant exposure to high soil temperature for two Agrostis species: Agrostis scabra Willd. , a species adapted to high-temperature soils in geothermal areas in Yellowstone National Park, and Agrostis stolonifera L. (cv. Penncross) a heat-sensitive grass widely used in cool-climate regions. Roots of A. scabra and A. stolonifera were exposed to soil temperature of 37 or 20°C, while shoots were exposed to 20°C for 28 days. Root viability decreased, and total root respiration increased for both species at 37°C. The decline in root viability and the increase in respiration rates were less pronounced for A. scabra than for A. stolonifera. A larger proportion of total root respiration was attributed to the AP in A. scabra compared with that in A. stolonifera when both species were exposed to 37°C. At 7 and 14 days at 3 7°C, the relative proportion of respiration passing through AP increased by 12 and 10%, respectively, in A. scabra, whereas in A. stolonifera, AP increased by 4 and 1%, respectively. Our results suggest that maintaining a higher proportion of AP at a high soil temperature may contribute to root thermo-tolerance in A. scabra in comparison with A. stolonifera, and alternative respiration may play an important role in plant adaptation to high soil temperature.
FORUM Why Are Some Proteins Allergens

The ability of certain proteins to induce an allergic response in susceptible individuals is well established. Symptoms can range from mild erythema or rhinitis, to acute, and possibly fatal, anaphylactic shock. Because such allergic responses require complex interactions between the protein and the immune system, they are notoriously difficult to predict. Nevertheless, it is clear that some proteins are intrinsically more allergenic than others. The challenge for toxicologists is to identify those characteristics that confer on proteins the potential to induce allergic sensitization and allergic disease. Here, we first consider the potential contribution that individual epitopes may make to the allergenicity of a protein. These are the minimal peptide units within proteins that can be recognized by the immune system and are a fundamental requirement for all immune responses, including those resulting in allergic sensitization. It appears that allergens must necessarily contain B-cell epitopes to which immunoglobulin E (IgE) can bind, and T-cell epitopes capable of inducing a type 2 T-lymphocyte response. Nevertheless, it appears doubtful that the presence of appropriate epitopes alone is sufficient to endow a protein with allergenic potential. We therefore consider also the contribution that other features and characteristics of proteins may make to their overall allergenicity. In particular, we consider the effects that resistance to proteolysis, post-translational glycosylation, and enzymatic activity may have. It appears that relative stability in simulated gastric fluid (SGF) sometimes correlates with allergenic activity. However, this is not universally true, and it is known that there are protein allergens, such as some of those associated with oral allergy syndrome, that are unstable. Nevertheless, if stability in SGF is associated with the intrinsic allergenicity of many proteins irrespective of the route of exposure, then this may reflect some more fundamental property of proteins, and possibly their stability in other biologic matrices and/or to intracellular proteases. Post-translational modification appears generally to enhance allergenicity, perhaps by increasing uptake and detection of the protein by the immune system. Some enzymatic activities also enhance allergenicity through what appear to be several different mechanisms, including nonspecific activation of cells participating in the immunologic response. Overall, it appears likely that many factors can contribute to the overall allergenicity of any given protein. Some, such as the presence of epitopes with allergenic potential, may be essential. Others, such as the glycosylation status, resistance to proteolysis, and enzymatic activity, may play a subsidiary but nevertheless critically important role. By better defining the limits within which these factors operate, we can hope to gain a better understanding of the fundamental origins of protein allergenicity, and therefore be in a position to identify and characterize the hazards and risks of allergic disease associated with novel proteins.
Validity and Reliability of Isometric-Bench for Knee Isometric Assessment

There is a strong need for a new, probably cheaper, smaller, and more portable isometric dynamometer. With this aim, we investigated the concurrent validity and reliability of a low-cost portable dynamometer to measure the isometric strength of the lower limb. Seventeen young participants (age 16.47 ± 0.51 years) were randomly assessed on three different days for knee flexion and extension isometric forces with two different devices: a commonly used isokinetic dynamometer (ISOC) and a portable isometric dynamometer prototype (ISOM). No significant differences were observed between the ISOC and the ISOM (all comparisons p > 0.05). Test–retest comparison showed the ISOM to have high reliability (ICC 0.879–0.990). This study showed that measurements with the ISOM could be performed without systematic bias and with high reliability. The ISOM is a device that is able to assess knee isometric strength with excellent concurrent validity and reliability.
1-(1-Arylethylpiperidin-4-yl)thymine Analogs as Antimycobacterial TMPK Inhibitors

A series of Mycobacterium tuberculosis TMPK (MtbTMPK) inhibitors based on a reported compound 3 were synthesized and evaluated for their capacity to inhibit MtbTMPK catalytic activity and the growth of a virulent M. tuberculosis strain (H37Rv). Modifications of the scaffold of 3 failed to afford substantial improvements in MtbTMPK inhibitory activity and antimycobacterial activity. Optimization of the substitution pattern of the D ring of 3 resulted in compound 21j with improved MtbTMPK inhibitory potency (three-fold) and H37Rv growth inhibitory activity (two-fold). Moving the 3-chloro substituent of 21j to the para-position afforded isomer 21h, which, despite a 10-fold increase in IC50-value, displayed promising whole cell activity (minimum inhibitory concentration (MIC) = 12.5 μM).
Recombinant Lactaptin Induces Immunogenic Cell Death and Creates an Antitumor Vaccination Effect in Vivo with Enhancement by an IDO Inhibitor

Natural compounds of various origins are intensively investigated for their antitumor activity. Potential benefits of antitumor therapy can be achieved when cytotoxic agents kill cancer cells and these dying cancer cells drive adoptive immunity to the tumor. This strategy was successfully demonstrated for chemotherapeutic drugs that induce immunogenic type of cell death (ICD) with release of DAMPs (danger associated molecular patterns) and exposure of “eat me” signals. In this study, we demonstrated that recombinant human milk peptide lactaptin (RL2) induces death of cancer cells with ICD hallmarks in vitro with the release of ATP and high-mobility group box 1 protein (HMGB1) and exposure of calreticulin and HSP70 on the external cell membrane. RL2-treated cancer cells were efficiently engulfed by phagocytic cells. Using the syngeneic mouse model, we demonstrated that RL2-treated MX-7 rhabdomyosarcoma cells confer long-term immune-mediated protection against challenge with live MX-7 cells. We also analyzed the combinatorial antitumor effect of vaccination with RL2-treated cells and the inhibition of indoleamine 2,3-dioxygenase (IDO) with ethyl pyruvate. Compared to solo anti-tumor immunization with RL2-treated cells, additional chemical inhibition of IDO demonstrated better long-term antitumor responses than vaccination alone.