Miracle-dz/UniFAR-FTUs huggingface dataset:
Blocking mitophagy does not improve fuel ethanol production in Saccharomyces cerevisiae

Ethanol fermentation is frequently performed under conditions of low nitrogen. In Saccharomyces cerevisiae, nitrogen limitation induces macroautophagy, including the selective removal of mitochondria, also called mitophagy. Shiroma and co-workers (2014) showed that blocking mitophagy by deletion of the mitophagy specific gene ATG32 increased the fermentation performance during the brewing of Ginjo sake. In this study, we tested if a similar strategy could enhance alcoholic fermentation in the context of fuel ethanol production from sugarcane in Brazilian biorefineries. Conditions that mimic the industrial fermentation process indeed induce Atg32-dependent mitophagy in cells of S. cerevisiae PE-2, a strain frequently used in the industry. However, after blocking mitophagy, no differences in CO2 production, final ethanol titres or cell viability were observed after five rounds of ethanol fermentation, cell recycling and acid treatment, as commonly performed in sugarcane biorefineries. To test if S. cerevisiae’s strain background influences this outcome, cultivations were carried out in a synthetic medium with strains PE-2, Ethanol Red (industrial) and BY (laboratory), with and without a functional ATG32 gene, under oxic and oxygen restricted conditions. Despite the clear differences in sugar consumption, cell viability and ethanol titres, among the three strains, we could not observe any improvement in fermentation performance related to the blocking of mitophagy. We conclude with caution that results obtained with Ginjo sake yeast is an exception and cannot be extrapolated to other yeast strains and that more research is needed to ascertain the role of autophagic processes during fermentation. Importance Bioethanol is the largest (per volume) ever biobased bulk chemical produced globally. The fermentation process is very well established, and industries regularly attain nearly 85% of maximum theoretical yields. However, because of the volume of fuel produced, even a small improvement will have huge economic benefits. To this end, besides already implemented process improvements, various free energy conservation strategies have been successfully exploited at least in laboratory strains to increase ethanol yields and decrease by-product formation. Cellular housekeeping processes have been an almost unexplored territory in strain improvement. Shiroma and co-workers previously reported that blocking mitophagy by deletion of the mitophagy receptor gene ATG32 in Saccharomyces cerevisiae led to a 2.12% increase in final ethanol titres during Japanese sake fermentation. We found in two commercially used bioethanol strains (PE-2 and Ethanol Red) that ATG32 deficiency does not lead to an improvement in cell viability or ethanol levels during fermentation with molasses or in a synthetic complete medium. More research is required to ascertain the role of autophagic processes during fermentation conditions.
The three-component reaction of 2-(2-oxopropyl)isoindoline-1,3-dione with alkyl isocyanides and aromatic carboxylic acids under catalyst-free conditions in water

A green and convenient protocol is described for the preparation of 1-(alkylamino)-3-(1,3dioxoisoindolin-2-yl)-2-methyl-1-oxopropan-2-yl benzoates via one-pot three-component reaction between 2-(2-oxopropyl)isoindoline-1,3-dione, an alkyl isocyanide and an aromatic carboxylic acid in water at room temperature. The methods used to follow the reactions are TLC and NMR, which indicated that there is no side product and the products were obtained without any purification. The structures of the products were deduced from their H NMR, C NMR and IR spectra. The present methodology offers several advantages such as a simple procedure, catalyst-free, mild reaction conditions, high yields, and the absence of any volatile and hazardous organic solvents.
Organization of the Catecholaminergic System in the Short-Lived Fish Nothobranchius furzeri

The catecholaminergic system has received much attention based on its regulatory role in a wide range of brain functions and its relevance in aging and neurodegenerative diseases. In the present study, we analyzed the neuroanatomical distribution of catecholaminergic neurons based on tyrosine hydroxylase (TH) immunoreactivity in the brain of adult Nothobranchius furzeri. In the telencephalon, numerous TH+ neurons were observed in the olfactory bulbs and the ventral telencephalic area, arranged as strips extending through the rostrocaudal axis. We found the largest TH+ groups in the diencephalon at the preoptic region level, the ventral thalamus, the pretectal region, the posterior tuberculum, and the caudal hypothalamus. In the dorsal mesencephalic tegmentum, we identified a particular catecholaminergic group. The rostral rhombencephalon housed TH+ cells in the locus coeruleus and the medulla oblongata, distributing in a region dorsal to the inferior reticular formation, the vagal lobe, and the area postrema. Finally, scattered TH+ neurons were present in the ventral spinal cord and the retina. From a comparative perspective, the overall organization of catecholaminergic neurons is consistent with the general pattern reported for other teleosts. However, Nothobranchius furzeri shows some particular features, including the presence of catecholaminergic cells in the midbrain. This work provides a detailed neuroanatomical map of the catecholaminergic system of Nothobranchius furzeri, a powerful aging model, also contributing to the phylogenetic understanding of one of the most ancient neurochemical systems.
BBB damage in aging causes brain iron deposits via astrocyte-neuron crosstalk and Hepc/Fpn1 pathway

During aging, iron accumulates in brain’s regions vulnerable to neurodegeneration: the cerebral cortex and the hippocampus. However, the mechanism of iron regulation in the brain remains scarce. Here, we demonstrated for the first time the involvement of the Hepcidin/Ferroportin1 pathway in brain iron metabolism during aging. We demonstrated the alteration of BBB integrity, that leads to increased iron permeability and deregulation of iron homeostasis during aging. We found that brain iron overload drives Hepcidin upregulation and, consequently, the inhibition of the iron exporter Ferroportin1, neuroinflammation and oxidative stress. Moreover, both in the cerebral cortex and hippocampus Ferroportin1 colocalizes with astrocytes, while the iron storage protein ferritin light-chain with neurons. This differential distribution suggests that astrocytes mediate iron shuttling and neurons are unable to metabolize it. Furthermore, we observed NCOA4-dependent ferritinophagy of ferritin heavy-chain isoforms determining the increase of light-chain enriched ferritin heteropolymers that are more efficient as iron chelators. Altogether, these data highlight the involvement of the Hepcidin/Ferroportin1 axis and NCOA4 during mice aging as a response to a higher iron influx to the brain.
Pain and the Emotional Brain: Affective Rather than Cognitive Processes Drive the Cortical Encoding of Pain

Background The experience of pain has been dissociated into two interwoven aspects: a sensory-discriminative aspect and an affective-motivational aspect. We aimed to explore which of the pain descriptors is more deeply rooted in the human brain. Findings Participants were asked to evaluate applied cold pain. The majority of the trials showed distinct ratings: some were rated higher for unpleasantness and others for intensity. We compared the relationship between functional data recorded from 7 tesla MRI with unpleasantness and intensity ratings and revealed a stronger relationship between cortical data and unpleasantness ratings. Conclusions The present study underlines the importance of the emotional-affective aspects of pain-related cortical processes in the brain. The findings corroborate previous studies showing a higher sensitivity to pain unpleasantness compared to ratings of pain intensity. For the processing of pain in healthy subjects, this effect may reflect the more direct and intuitive evaluation of emotional aspects of the pain system, which is to prevent harm and to preserve the physical integrity of the body.
How dominant alleles influence progress toward speciation by natural selection

Extrinsic post-zygotic isolating barriers occur when hybrids have poor fitness in the parental habitat(s) and ultimately arise as a consequence of interactions between the alleles underlying adaptation. Most models of speciation via natural selection consider only alleles that have additive phenotypic effects, even though many quantitative trait loci exhibit some dominance. We used computer simulations to evaluate how hybrid fitness differs when parent populations adapt from either (i) mutations that are strictly additive or (ii) mutations with a range of dominance coefficients. Compared to the additive case, we find that introducing dominance invariably reduces hybrid fitness when parents adapt to identical optima (i.e., parallel selection) because hybrids express transgressive phenotypes that are maladaptive in the common parental niche. The effect of dominance becomes less negative as selection tends toward completely divergent. When selection is completely divergent, dominance can increase hybrid fitness over the additive case because chance events result in unequal mean dominance among populations and cause hybrids to resemble one of the parents rather than a maladapted intermediate phenotype. However, when the adapting population has many traits (i.e., high ‘dimensionality’) dominance always reduces hybrid fitness over the additive case because hybrids express maladaptive transgressive phenotypes in traits under stabilizing selection. Our results indicate that dominant alleles facilitate progress toward speciation via parallel natural selection, and might either increase or decrease the efficacy of divergent selection for speciation.
An Improved Codon Modeling Approach for Accurate Estimation of the Mutation Bias

Nucleotide composition in protein-coding sequences is the result of the equilibrium between mutation and selection. In particular, the nucleotide composition differs between the three coding positions, with the third position showing more extreme composition than the first and the second positions. Yet, phylogenetic codon models do not correctly capture this phenomenon and instead predict that the nucleotide composition should be the same for all 3 positions of the codons. Alternatively, some models allow for different nucleotide rates at the three positions, a problematic approach since the mutation process should in principle be blind to the coding structure and homogeneous across coding positions. Practically, this misconception could have important consequences in modelling the impact of GC-biased gene conversion (gBGC) on the evolution of protein-coding sequences, a factor which requires mutation and fixation biases to be carefully disentangled. Conceptually, the problem comes from the fact that phylogenetic codon models cannot correctly capture the fixation bias acting against the mutational pressure at the mutation-selection equilibrium. To address this problem, we present an improved codon modeling approach where the fixation rate is not seen as a scalar anymore, but as a tensor unfolding along multiple directions, which gives an accurate representation of how mutation and selection oppose each other at equilibrium. Thanks to this, this modelling approach yields a reliable estimate of the mutational process, while disentangling fixation probabilities in different directions.
Antimicrobial activity of flavonoids glycosides and pyrrolizidine alkaloids from propolis of Scaptotrigona aff. postica

Stingless bees belonging to the Meliponinae subfamily, are known as meliponines. Scaptotrigona affinis postica Latreille, 1807 from northeast of Brazil is popularly known as ‘tubi’ in Maranhão State. Scaptotrigona, which is widely distributed in neotropical regions, includes species that build their hives in pre-existing cavities. Flavones di-C-glycosides, and the pyrrolizidine alkaloid 7-(3-methoxy-2-methylbutyryl)-9-echimidinylretronecine were reported previously in propolis from S. postica. Fractions 40 AEP and 40 MEP from ethanolic extract were analyzed by LC-MS. The chromatographic profile of fractions 40 AEP and 40 MEP revealed the presence of many pyrrolizidine alkaloids, among them, lithosenine (14), lithosenine arabinoside (19), 7-angeloyl-9-(2,3- dihydroxybutyryl) retronecine (1), 7-(2-methylbutyryl) retronecine (3), 9-sarracinoylretronecine (13) and viridinatine (8),besides the flavonoids schaftoside (15), aromadendrin-7-O-methyl ether (12), 7-methoxy-5,6,3’,4’,5’,6’-hexahydroxy-flavone-3-O-glucuronide (11), mangiferin (10) and 3-O-methyl mangiferin (17). Fractions 40 AEP and 40 MEP showed antimicrobial activity against Gram negative bacteria, including Escherichia coli D31-streptomycin resistant. Cell viability was expressed in terms of the relative absorbance of treated and untreated cells (control). There was no statistical difference between treated and untreated cells.
FSCMA TYPE BINARIES

FSCMa type stars is a group of ∼70 objects formerly known as unclassified stars with the B[e] phenomenon. Their very strong emission-line spectra in combination with a nearly main-sequence luminosity suggest the binary nature for them. They possess strong IR excesses due to radiation of circumstellar dust that implies a compact distribution probably in a circumbinary disk. Our long-term spectroscopic monitoring revealed neutral metal lines, which always include that of Li i 6708 Å, in the spectra of some FSCMa objects indicating the presence of a cool star. We present a summary of our results with a first overview of FSCMa type binaries and review possible implications for the nature and evolutionary status of the entire group.
ARTICLE TEMPLATE Place Facets: A Systematic Literature Review

Place is a central concept in geography and a topic of interest in the social sciences, urban planning, architecture, and most recently in information science. The notion of place has therefore been studied with different foci of interest. Consequently, heterogeneous terminologies, conceptualizations, models, and ontologies have been proposed to capture this elusive concept. Yet these studies complement each other. Utilizing the concept of place facet as a particular type of information about place, in this review paper we bridge these multidisciplinary studies about place. We collect the different facets of place introduced in the literature and synthesize place characteristics by categorizing the identified facets. Finally, we discuss future directions for place-related research.
Customs and Rituals among settled Gujjars of Jammu District in J&K

This paper is an attempt to study the Customs and Rituals among settled Gujjars of Jammu District in J&K. Customs are nothing but accepted and common ways of acting. They are very much responsible for maintenance of social values and objectives. Tradition, as a result of transference from generation to other gets strengthened by the new generations. These strengthened traditions are called
A Two-Step Framework for Parkinson’s Disease Classiﬁcation: Using Multiple One-Way ANOVA on Speech Features and Decision Trees

We propose a two-step classiﬁcation framework to diagnose Parkinson’s Disease (PD) using speech samples. At the ﬁrst stage, multiple one-way ANalysis Of VAriance (ANOVA) is used on independent subsets of vocal features to extract the best set of features from each speech processing algorithm. These extracted feature subsets are then merged with other baseline vocal features (shimmer, jitter, pitch, harmonicity, vocal fold, and fundamental frequency parameters) to form the training feature set. In the second step, this combined training set is used to train an extreme gradient boosting (XG-Boost) classiﬁcation model, which is a decision tree based algorithm. The overall model performance was scored and evaluated using the Receiver Operating Characteristic Area Under Curve (ROC AUC), F-Measure, Matthews Correlation Coefﬁcient (MCC), and accuracy. It was then compared with benchmarked statistical classiﬁers and other studies that use different combinations of features from this PD dataset. We apply one-way ANOVA on different speech feature sets to extract the best features without losing useful vocal information. Our classiﬁcation performance outperforms state-of-the-art PD classiﬁcation models that use generic feature selection methods or use only one or more of the vocal feature subsets.
A FEW RESULTS REGARDING THRESHOLDS

OF THE DISSERTATION A Few Results Regarding Thresholds By KEITH FRANKSTON Dissertation Director: Jeff Kahn This thesis consists of four parts, each regarding a topic from extremal combinatorics. While only Chapters 3 and 4 are directly related, each in some way concerns the concept of thresholds, whether providing a new sharp threshold result for regular properties (in the case of Chapter 2), proving specific graph theoretic thresholds (in the case of Chapter 5), or showing how different thresholds are related (as in Chapters 3 and 4). In Chapter 2, we answer a question of Cameron, Frankl, and Kantor from 1989, extending a result of Ellis and Narayanan. They verified a conjecture of Frankl, that any 3-wise intersecting family of subsets of {1, 2, . , n} admitting a transitive automorphism group has cardinality o(2n). However, a construction of Frankl demonstrates that the same conclusion need not hold under the weaker constraint of being regular. We show that the restriction of admitting a transitive automorphism group may be relaxed significantly: we prove that any 3-wise intersecting family of subsets of {1, 2, . , n} that is regular and increasing has cardinality o(2n). In Chapter 3, we prove a conjecture of Talagrand, itself a fractional version of the “expectation-threshold” conjecture of Kahn and Kalai. We show that for any increasing family F on a finite set X, we have pc(F) = O(qf (F) ln `(F)), where pc(F) and qf (F) are the threshold and “fractional expectation-threshold” of F , and `(F) is the maximum size of a minimal member of F . This easily implies several heretofore difficult results and
Effects of Earth system feedbacks on the potential mitigation of large-scale tropical forest restoration

Abstract. To achieve the Paris Agreement requires aggressive mitigation strategies alongside negative emission technologies. Recent studies suggest that increasing tree cover can make a substantial contribution to negative emissions, with the tropics being the most suitable region from a biogeophysical perspective. Yet these studies typically do not account for subsequent carbon cycle and climate responses to large-scale land-use change. Here we quantify the maximum potential temperature and CO 2 benefits from pantropical forest restoration, including the Earth system response, using a fully coupled, emission-driven Earth system model (HadGEM2-ES). We perform an idealised experiment where all land use in the tropics is stopped and vegetation is allowed to recover, on top of an aggressive mitigation scenario (RCP2.6). We find that tropical restoration of 1529 Mha increases carbon stored in live biomass by 130 Pg C by 2100 CE. Whilst avoiding deforestation and tropical restoration in the tropics removes 42 Pg C compared to RCP2.6, the subsequent reduction in extratropical and ocean carbon uptake means that carbon in the atmosphere only reduces by 18 Pg C by 2100. The resulting small CO 2 (9 ppm) benefit does not translate to a detectable reduction in global surface air temperature compared to the control experiment. The greatest carbon benefit is achieved 30–50 years after restoration before the Earth system response adjusts to the new land-use regime and declining fossil fuel use. Comparing our results with previous modelling studies, we identify two model-independent key points: (i) in a world where emission reductions follow the Paris Agreement, restoration is best deployed immediately, and (ii) the global carbon cycle response to reduced emissions limits the efficacy of negative emissions technologies by more than half. We conclude that forest restoration can reduce peak CO 2 mid-century, but it can only modestly contribute to negative emissions.
handling abnormalities in early-onset muscle diseases: novel concepts and perspectives

1. Departments of Biomedicine and Anesthesia, Basel University Hospital, 4031 Basel, Switzerland. 2. Department of Life Sciences, general pathology section, University of Ferrara, 44100 Ferrara, Italy. 3. Department of Paediatric Neurology, Neuromuscular Service, Evelina Children’s Hospital, St Thomas’ Hospital, London, United Kingdom. 4. Randall Division for Cell and Molecular Biophysics, Muscle Signalling Section, King’s College, London, United Kingdom. 5. Department of Basic and Clinical Neuroscience , IoPPN, King’s College, London, United Kingdom 6. Department of Neurology, Radboud University Medical Centre, Nijmegen, The Netherlands. 7. Dubowitz Neuromuscular Centre, Institute of Child Health, University College London, United Kingdom
A BRIEF SURVEY OF HIGGS BUNDLES UN ESTUDIO CONCISO DE FIBRADOS DE HIGGS

Considering a compact Riemann surface of genus greater or equal than two, a Higgs bundle is a pair composed of a holomorphic bundle over the Riemann surface, joint with an auxiliar vector field, so-called Higgs field. This theory started around thirty years ago, with Hitchin’s work, when he reduced the self-duality equations from dimension four to dimension two, and so, studied those equations over Riemann surfaces. Hitchin baptized those fields as Higgs fields because in the context of physics and gauge theory, they describe similar particles to those described by the Higgs bosson. Later, Simpson used the name Higgs bundle for a holomorphic bundle together with a Higgs field. Today, Higgs bundles are the subject of research in several areas such as non-abelian Hodge theory, Langlands, mirror symmetry, integrable systems, quantum field theory (QFT), among others. The main purposes here are to introduce these objects, and to present a brief but complete construction of the moduli space of Higgs bundles.
TITLE PAGE TITLE: Proof-of-concept pilot study on comprehensive spatiotemporal intra-patient heterogeneity for colorectal cancer with liver metastasis

1. Centre for Biosystems and Genome Network Medicine, Ioannina University, 45110 Ioannina, Greece. 2. Department of Surgery, Ioannina University Hospital, 45500 Ioannina, Greece. 3. Department of Pathology, Ioannina University Hospital, 45500 Ioannina, Greece. 4. NIPD Genetics, 2409, Nicosia, Cyprus 5. Cancer Biobank Centre, Ioannina University, Ioannina, 45110, Greece 6. University of Nicosia Medical School, 2417 Nicosia, Cyprus 7. Department of Systems Biology, Biomedical Research Foundation of the Academy of Athens, Athens, 11527, Greece