Miracle-dz/UniFAR-FTUs huggingface dataset:
The Tomato Genome Encodes SPCH, MUTE, and FAMA Candidates That Can Replace the Endogenous Functions of Their Arabidopsis Orthologs

Stomatal abundance determines the maximum potential for gas exchange between the plant and the atmosphere. In Arabidopsis, it is set during organ development through complex genetic networks linking epidermal differentiation programs with environmental response circuits. Three related bHLH transcription factors, SPCH, MUTE, and FAMA, act as positive drivers of stomata differentiation. Mutant alleles of some of these genes sustain different stomatal numbers in the mature organs and have potential to modify plant performance under different environmental conditions. However, knowledge about stomatal genes in dicotyledoneous crops is scarce. In this work, we identified the Solanum lycopersicum putative orthologs of these three master regulators and assessed their functional orthology by their ability to complement Arabidopsis loss-of-function mutants, the epidermal phenotypes elicited by their conditional overexpression, and the expression patterns of their promoter regions in Arabidopsis. Our results indicate that the tomato proteins are functionally equivalent to their Arabidopsis counterparts and that the tomato putative promoter regions display temporal and spatial expression domains similar to those reported for the Arabidopsis genes. In vivo tracking of tomato stomatal lineages in developing cotyledons revealed cell division and differentiation histories similar to those of Arabidopsis. Interestingly, the S. lycopersicum genome harbors a FAMA-like gene, expressed in leaves but functionally distinct from the true FAMA orthologue. Thus, the basic program for stomatal development in S. lycopersicum uses key conserved genetic determinants. This opens the possibility of modifying stomatal abundance in tomato through previously tested Arabidopsis alleles conferring altered stomata abundance phenotypes that correlate with physiological traits related to water status, leaf cooling, or photosynthesis.
Deciphering HER2 Breast Cancer Disease: Biological and Clinical Implications

The main obstacle for designing effective treatment approaches in breast cancer is the extensive and the characteristic heterogeneity of this tumor. The vast majority of critical genomic changes occurs during breast cancer progression, creating a significant variability within primary tumors as well as between the primary breast cancer and their metastases, a hypothesis have already demonstrated in retrospective studies (1). A clear example of this is the HER2-positive breast cancer. In these tumors, we can find all of the transcriptional subtypes of breast cancer, even the basal like or luminal A subtypes. Although the HER2-enriched is the most representative transcriptional subtype in the HER2-positive breast cancer, we can find it too in breast cancers with HER2-negative status. This intrinsic subtype shows a high expression of the HER2 and is associated with proliferation-related genes clusters, among other features. Therefore, two hypotheses can be suggested. First, the HER2 amplification can be a well-defined driver event present in all of the intrinsic subtypes, and not a subtype marker isolated. Secondly, HER2-enriched subtype can have a distinctive transcriptional landscape independent of HER2 amplification. In this review, we present an extensive revision about the last highlights and advances in clinical and genomic settings of the HER2-positive breast cancer and the HER2-enriched subtype, in an attempt to improving the knowledge of the underlying biology of both entities and to explaining the intrinsic heterogeneity of HER2-positive breast cancers.
Fast Screening of Inhibitor Binding/Unbinding Using Novel Software Tool CaverDock

Protein tunnels and channels are attractive targets for drug design. Drug molecules that block the access of substrates or release of products can be efficient modulators of biological activity. Here, we demonstrate the applicability of a newly developed software tool CaverDock for screening databases of drugs against pharmacologically relevant targets. First, we evaluated the effect of rigid and flexible side chains on sets of substrates and inhibitors of seven different proteins. In order to assess the accuracy of our software, we compared the results obtained from CaverDock calculation with experimental data previously collected with heat shock protein 90α. Finally, we tested the virtual screening capabilities of CaverDock with a set of oncological and anti-inflammatory FDA-approved drugs with two molecular targets—cytochrome P450 17A1 and leukotriene A4 hydrolase/aminopeptidase. Calculation of rigid trajectories using four processors took on average 53 min per molecule with 90% successfully calculated cases. The screening identified functional tunnels based on the profile of potential energies of binding and unbinding trajectories. We concluded that CaverDock is a sufficiently fast, robust, and accurate tool for screening binding/unbinding processes of pharmacologically important targets with buried functional sites. The standalone version of CaverDock is available freely at https://loschmidt.chemi. muni.cz/caverdock/ and the web version at https://loschmidt.chemi. muni.cz/caverweb/.
The Delta-Subunit Selective GABAA Receptor Modulator, DS2, Improves Stroke Recovery via an Anti-inflammatory Mechanism

Inflammatory processes are known to contribute to tissue damage in the central nervous system (CNS) across a broad range of neurological conditions, including stroke. Gamma amino butyric acid (GABA), the main inhibitory neurotransmitter in the CNS, has been implicated in modulating peripheral immune responses by acting on GABAA receptors on antigen-presenting cells and lymphocytes. Here, we investigated the effects and mechanism of action of the delta-selective compound, DS2, to improve stroke recovery and modulate inflammation. We report a decrease in nuclear factor (NF)-κB activation in innate immune cells over a concentration range in vitro. Following a photochemically induced motor cortex stroke, treatment with DS2 at 0.1 mg/kg from 1 h post-stroke significantly decreased circulating tumor necrosis factor (TNF)-α, interleukin (IL)-17, and IL-6 levels, reduced infarct size and improved motor function in mice. Free brain concentrations of DS2 were found to be lower than needed for robust modulation of central GABAA receptors and were not affected by the presence and absence of elacridar, an inhibitor of both P-glycoprotein and breast cancer resistance protein (BCRP). Finally, as DS2 appears to dampen peripheral immune activation and only shows limited brain exposure, we assessed the role of DS2 to promote functional recovery after stroke when administered from 3-days after the stroke. Treatment with DS2 from 3-days post-stroke improved motor function on the grid-walking, but not on the cylinder task. These data highlight the need to further develop subunit-selective compounds to better understand change in GABA receptor signaling pathways both centrally and peripherally. Importantly, we show that GABA compounds such as DS2 that only shows limited brain exposure can still afford significant protection and promote functional recovery most likely via modulation of peripheral immune cells and could be given as an adjunct treatment.
The Timeout in Sports: A Study of Its Effect on Volleyball

The purpose of this study was to analyse the variables (lost rallies and score difference) that determine the timeout effect (positive or no effect) in volleyball, in balanced and unbalanced sets. 232 timeouts, requested by the coaches of 66 male and female teams participating in the Spanish Championship in the Under-14 and Under-16 categories, were analysed. The variables considered in this study were timeout effects, lost rallies and score differences. To analyse the timeout effect, a binary logistic regression model was applied. The results of this model show that, in balanced sets, the variables that predict the timeout effect are the number of rallies (≤2 lost rallies) and the score difference (2–3 points), whilst in unbalanced sets, and the variable that predicts the timeout effect is the number of lost rallies (3 lost rallies). These results show the importance of bearing these variables in mind when timeouts are managed and requested by coaches, in order to optimise the team’s performance.
El Tor Biotype Vibrio cholerae Activates the Caspase-11-Independent Canonical Nlrp3 and Pyrin Inflammasomes

Vibrio cholerae is a Gram-negative enteropathogen causing potentially life-threatening cholera disease outbreaks, for which the World Health Organization currently registers 2–4 million cases and ~100.000 cholera-associated deaths annually worldwide. Genomic Vibrio cholerae research revealed that the strains causing this ongoing cholera pandemic are members of the El Tor biotype, which fully replaced the Classical biotype that caused former cholera pandemics. While both of these biotypes express the characteristic Cholera Toxin (CT), the El Tor biotype additionally expresses the accessory toxins hemolysin (hlyA) and multifunctional auto-processing repeat-in-toxin (MARTX). Previous studies demonstrated that the Classical biotype of Vibrio cholerae triggers caspase-11-dependent non-canonical inflammasome activation in macrophages following CT-mediated cytosolic delivery of LPS. In contrast to the Classical biotype, we here show that El Tor Vibrio cholerae induces IL-1β maturation and secretion in a caspase-11- and CT-independent manner. Instead, we show that El Tor Vibrio cholerae engages the canonical Nlrp3 inflammasome for IL-1β secretion through its accessory hlyA toxin. We further reveal the capacity of this enteropathogen to engage the canonical Pyrin inflammasome as an accessory mechanism for IL-1β secretion in conditions when the pro-inflammatory hlyA-Nlrp3 axis is blocked. Thus, we show that the V. cholerae El Tor biotype does not trigger caspase-11 activation, but instead triggers parallel Nlrp3- and Pyrin-dependent pathways toward canonical inflammasome activation to induce IL-1β-mediated inflammatory responses. These findings further unravel the complex inflammasome activating mechanisms that can be triggered when macrophages face the full arsenal of El Tor Vibrio cholerae toxins, and as such increase our understanding of host-pathogen interactions in the context of the Vibrio cholerae biotype associated with the ongoing cholera pandemic.
Resveratrol Reverses Retinoic Acid Resistance of Anaplastic Thyroid Cancer Cells via Demethylating CRABP2 Gene

Background: Cellular retinoic acid binding protein 2 (CRABP2) mediates retinoic acid/RA anti-cancer pathways. Resveratrol effectively reverses RA tolerance and upregulates CRABP2 expression of anaplastic thyroid cancer cell line THJ-11T. As DNA methylation is responsible for CRABP2 silencing, the CRABP2 methylation status of THJ-11T cells and the demethylating effect of resveratrol on this gene are elucidated. Materials and methods: The statuses of CRABP2 expression and methylation and the levels of DNA methyltransferases (DNMTs) DNMT1, DNMT3A, and DNMT3B of THJ-11T cells were examined before and after resveratrol treatment via multiple experimental methods. The human medulloblastoma UW228-2 cell line was cited as the control of CRABP2 methylation and gemcitabine as the demethylator control. Results: RT-PCR, immunocytochemical staining and Western blotting showed that resveratrol significantly increased the CRABP2 expression and RA sensitivity of THJ-11T and UW228-2 cells. Bisulfite sequencing showed five CpG methylation sites at the CRABP2 promoter region of both cell lines, which were partially (3/5) demethylated by resveratrol and totally (5/5) by gemcitabine. DNMT1, DNMT3A, and DNMT3B were reduced in UW228-2 cells and DNMT1 and DNMT3A were reduced in THJ-11T cells after resveratrol treatment in a time-related fashion. Conclusion: Resveratrol is able to erase CRABP2 methylation and can thereby increase the RA sensitivity of THJ-11T and UW228-2 cells. This study demonstrates the additional value of the natural polyphenolic compound resveratrol as a demethylator in cancer treatments.
Surveillance During REM Sleep for the First-Night Effect

We experience disturbed sleep in a new place, and this effect is known as the first-night effect (FNE) in sleep research. We previously demonstrated that the FNE is associated with a surveillance system in one brain hemisphere during NREM sleep, which manifests as interhemispheric asymmetry in sleep depth in the default-mode network (DMN) and increased vigilance toward monitoring external stimuli. This surveillance system may be useful for protecting vulnerable sleepers from abnormal events in unfamiliar environments. The present study investigated whether a similar surveillance system is exhibited during rapid eye movement (REM) sleep. The impacts of the FNE could be different between the phasic period, in which eyes move rapidly, and the tonic period, in which eye movement ceases, of REM sleep; without the FNE, vigilance to external stimuli is generally reduced during the phasic period but not the tonic period. Thus, REM sleep was split into phasic and tonic periods. First, we replicated previous findings showing interhemispheric asymmetry in delta activity in the DMN associated with the FNE during NREM sleep. However, during REM sleep, interhemispheric asymmetry in delta activity or theta activities, two oscillatory activities during REM sleep, was not found during the phasic or tonic periods. Next, we tested whether vigilance, as measured by evoked brain responses (P2) to deviant tones, associated with the FNE was increased in one hemisphere during REM sleep. The P2 amplitudes during the phasic period were augmented by the FNE on day 1 and were significantly larger than those on day 2 when the FNE was not present. In contrast, the P2 amplitudes during the tonic period were not different across days. The P2 amplitudes showed no interhemispheric asymmetry during the phasic or tonic periods. These results suggest that while the surveillance system exhibits interhemispheric asymmetry in sleep depth and vigilance during NREM sleep, this system shows no interhemispheric asymmetry in oscillatory activities and exhibits increased vigilance in both hemispheres only during the phasic period of REM sleep. Therefore, the surveillance system associated with the FNE may involve different mechanisms during NREM and REM sleep.
Ju l 2 01 4 Search for CP violation in D 0 → π 0 π 0 decays

N. K. Nisar, K. Trabelsi, G. B. Mohanty, T. Aziz, A. Abdesselam, I. Adachi, H. Aihara, K. Arinstein, D. M. Asner, V. Aulchenko, T. Aushev, R. Ayad, S. Bahinipati, A. M. Bakich, A. Bala, V. Bansal, P. Behera, K. Belous, V. Bhardwaj, A. Bobrov, G. Bonvicini, A. Bozek, M. Bračko, T. E. Browder, D. Červenkov, B. G. Cheon, K. Chilikin, K. Cho, V. Chobanova, Y. Choi, D. Cinabro, J. Dalseno, 53 M. Danilov, 32 Z. Doležal, Z. Drásal, A. Drutskoy, 32 D. Dutta, K. Dutta, S. Eidelman, D. Epifanov, H. Farhat, J. E. Fast, T. Ferber, V. Gaur, N. Gabyshev, S. Ganguly, A. Garmash, Y. M. Goh, B. Golob, 20 T. Hara, H. Hayashii, X. H. He, Y. Hoshi, W. -S. Hou, T. Iijima, 34 A. Ishikawa, R. Itoh, Y. Iwasaki, T. Iwashita, J. H. Kang, T. Kawasaki, C. Kiesling, D. Y. Kim, J. B. Kim, J. H. Kim, M. J. Kim, Y. J. Kim, K. Kinoshita, B. R. Ko, P. Kodyš, S. Korpar, 20 P. Križan, 20 P. Krokovny, T. Kuhr, R. Kumar, A. Kuzmin, Y. -J. Kwon, J. S. Lange, S. -H. Lee, L. Li Gioi, J. Libby, D. Liventsev, P. Lukin, B. Macek, D. Matvienko, K. Miyabayashi, H. Miyata, R. Mizuk, 32 A. Moll, 53 R. Mussa, E. Nakano, M. Nakao, M. Nayak, E. Nedelkovska, O. Nitoh, S. Ogawa, S. Okuno, P. Pakhlov, 32 G. Pakhlova, H. Park, H. K. Park, T. K. Pedlar, T. Peng, R. Pestotnik, M. Petrič, L. E. Piilonen, E. Ribežl, M. Ritter, M. Röhrken, A. Rostomyan, Y. Sakai, S. Sandilya, L. Santelj, T. Sanuki, Y. Sato, O. Schneider, G. Schnell, 11 C. Schwanda, A. J. Schwartz, D. Semmler, K. Senyo, O. Seon, M. E. Sevior, M. Shapkin, V. Shebalin, T. -A. Shibata, J.-G. Shiu, B. Shwartz, F. Simon, 53 Y. -S. Sohn, A. Sokolov, E. Solovieva, S. Stanič, M. Starič, M. Steder, J. Stypula, T. Sumiyoshi, G. Tatishvili, Y. Teramoto, M. Uchida, T. Uglov, 33 S. Uno, P. Urquijo, Y. Usov, S. E. Vahsen, C. Van Hulse, P. Vanhoefer, G. Varner, K. E. Varvell, M. N. Wagner, C. H. Wang, M. -Z. Wang, P. Wang, Y. Watanabe, K. M. Williams, E. Won, J. Yamaoka, Y. Yamashita, S. Yashchenko, Y. Yook, Z. P. Zhang, V. Zhilich, V. Zhulanov, and A. Zupanc
FNR-Dependent RmpA and RmpA2 Regulation of Capsule Polysaccharide Biosynthesis in Klebsiella pneumoniae

Fumarate nitrate reduction regulator (FNR) is a direct oxygen-responsive transcriptional regulator containing an iron-sulfur (Fe–S) cluster. During anaerobic growth, the [4Fe–4S] cluster in FNR (holo-FNR) binds specifically to DNA, whereas exposure to oxygen results in the loss of its DNA-binding activity via oxidation of the [4Fe–4S] cluster. In this study, we aimed to investigate the role of FNR in regulation of capsular polysaccharide (CPS) biosynthesis, serum resistance, and anti-phagocytosis of K. pneumoniae. We found that the CPS amount in K. pneumoniae increased in anaerobic conditions, compared to that in aerobic conditions. An fnr deletion mutant and a site-directed mutant (fnr3CA), with the three cysteines (C20, C23, and C29) replaced with alanines to mimic an FNR lacking the [4Fe-4S] cluster, showed marked increase in CPS amount under anaerobic conditions. A promoter-reporter assay and qRT-PCR confirmed that the transcription of the cps genes was repressed by holo-FNR. In addition, we found that holo-FNR could repress the transcription of rmpA and rmpA2, encoding cps transcriptional activators. Deletion of rmpA or rmpA2 in the Δfnr strain reduced CPS biosynthesis, suggesting that RmpA and RmpA2 participated in the holo-FNR–mediated repression of cps transcription, thereby regulating the CPS amount, serum resistance, and anti-phagocytosis. Taken together, our results provided evidence that RmpA and RmpA2 participated in the holo-FNR–mediated repression of CPS biosynthesis, and resistance to the host defense in response to oxygen availability.
Effects of Chronic and Experimental Acute Masseter Pain on Precision Biting Behavior in Humans

Chronic pain in the orofacial region is common worldwide. Pain seems to affect the jaw motor control. Hence, temporomandibular disorders (TMD) are often accompanied by pain upon chewing, restricted mouth opening and impaired maximal bite forces. However, little is known on the effects of pain, in particular the effects of chronic jaw muscle pain on precision biting. The aim of the study was to investigate the effect of chronic and acute jaw muscle pain on oral motor control during precision biting in humans. Eighteen patients with chronic masseter muscle pain and 18 healthy participants completed the experiment. All participants were examined according to the Diagnostic Criteria for TMD. Experimental acute pain was induced by bilateral, simultaneous sterile hypertonic saline infusions into the healthy masseter muscles. A standardized hold and split biting task was used to assess the precision biting. The data was analyzed with non-parametric statistical tests. The results showed no significant differences in the hold forces, split forces, durations of split or peak split rates within or between the pain and pain-free conditions. The mean split rate increased significantly compared to baseline values both in the chronic patients and the pain-free condition. However, this increase was not evident in the experimental acute pain condition. Further, there were no significant differences in the mean split rates between the conditions. The data suggest that jaw muscle pain does not seem to alter precision biting in humans, however, the possibility that a nociceptive modulation of spindle afferent activity might have occurred but compensated for cannot be ruled out.
Alteration of Cholesterol Sulfate/Seminolipid Ratio in Semen Lipid Profile of Men With Oligoasthenozoospermia

The reduction of sperm motility and count, or oligoasthenozoospermia, is one of the major causes of reduced fertility or infertility in men. Lipid composition of spermatozoa is important in determining their functional characteristics, in particular on motility, acrosomal exocytosis or fusogenic properties of the sperm. Here we investigated the levels of semen lipids in 11 infertile patients with severe oligoasthenozoospermia and 9 normozoospermic subjects with normal motility values. Sperm polar and neutral lipids were analyzed by thin-layer chromatography (TLC) and matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Semen of patients with oligoasthenozoospermia showed a reduction of the degree of fatty acid unsaturation in the phospholipids chains that might affect the membrane fluidity. Furthermore, a significant higher cholesterol sulfate/seminolipid ratio was found in semen of oligoasthenozoospermic patients than in subjects with normal motility values, suggesting a critical role of sulfolipids in semen quality. The results may facilitate the understanding of the role of lipids on male fertility and offer interesting perspectives to find innovative treatments for oligoasthenozoospermia.
Phytohormone Mediation of Interactions Between Plants and Non-Symbiotic Growth Promoting Bacteria Under Edaphic Stresses

The capacity of rhizoshere bacteria to influence plant hormonal status, by bacterial production or metabolism of hormones, is considered an important mechanism by which they promote plant growth, and productivity. Nevertheless, inoculating these bacteria into the plant rhizosphere may produce beneficial or detrimental results depending on bacterial effects on hormone composition and quantity in planta, and the environmental conditions under which the plants are growing. This review considers some effects of bacterial hormone production or metabolism on root growth and development and shoot physiological processes. We analyze how these changes in root and shoot growth and function help plants adapt to their growth conditions, especially as these change from optimal to stressful. Consistent effects are addressed, along with plant responses to specific environmental stresses: drought, salinity, and soil contamination (with petroleum in particular).
Improving Short- and Long-Term Genetic Gain by Accounting for Within-Family Variance in Optimal Cross-Selection

The implementation of genomic selection in recurrent breeding programs raised several concerns, especially that a higher inbreeding rate could compromise the long term genetic gain. An optimized mating strategy that maximizes the performance in progeny and maintains diversity for long term genetic gain on current and yet unknown future targets is essential. The optimal cross selection approach aims at identifying the optimal set of crosses maximizing the expected genetic value in the progeny under a constraint on diversity in the progeny. Usually, optimal cross selection does not account for within family selection, i.e. the fact that only a selected fraction of each family serves as candidate parents of the next generation. In this study, we consider within family variance accounting for linkage disequilibrium between quantitative trait loci to predict the expected mean performance and the expected genetic diversity in the selected progeny of a set of crosses. These predictions rely on the method called usefulness criterion parental contribution (UCPC). We compared UCPC based optimal cross selection and optimal cross selection in a long term simulated recurrent genomic selection breeding program considering overlapping generations. UCPC based optimal cross selection proved to be more efficient to convert the genetic diversity into short and long term genetic gains than optimal cross selection. We also showed that using the UCPC based optimal cross selection, the long term genetic gain can be increased with only limited reduction of the short term commercial genetic gain.