bluuebunny/crossref_metadata_2025_split huggingface dataset:
The drought-responsiveZmFDL1gene regulates cuticle biosynthesis and cuticle-dependent leaf permeability
Authors: Castorina Giulia , Domergue Frédéric , Chiara Matteo , Zilio Massimo , Persico Martina , Ricciardi Valentina , Horner David Stephen , Consonni Gabriella 
Published: March 2020

AbstractIn higher plants, the outer surface of the aerial parts is covered by the cuticle, a complex lipid layer that constitutes a barrier against damages caused by environmental factors and provides protection against non-stomatal water loss. We show in this study that cuticle deposition, during the juvenile phase of in maize (Zea mays) plant development, and cuticle-dependent leaf permeability are controlled by the MYB transcription factorZmMYB94/FUSED LEAVES1(ZmFDL1).Biochemical analysis showed that infdl1-1mutant seedlings at the coleoptile stage both cutin and wax biosynthesis and deposition were altered. Among cutin compounds, ω-hydroxy fatty acids and polyhydroxy-fatty acids were specifically affected, while the reduction of epicuticular waxes, was mainly observed in primary long chain alcohols, and to a minor extent, long-chain wax esters.Transcriptome analysis allowed the identification of novel candidate genes involved in lipid metabolism and the assembly of a proposed pathway for cuticle biosynthesis in maize. Lack of ZmFDL1 affects the expression of genes located in different modules of the pathway and correspondence between gene transcriptional variations and biochemical defects have been highlighted.A decrease in cuticle-dependent leaf permeability was observed in maize seedlings exposed to drought as well as ABA treatment, which implies coordinated changes in the transcript levels ofZmFDL1and associated genes. Overall, our results suggest that the response to water stress implies the activation of wax biosynthesis and the involvement of by both ZmFDL1 and ABA regulatory pathways.One-Sentence SummaryCuticle biosynthesis and cuticle-mediated drought-response during the juvenile phase of maize plant growth, are regulated by the MYB transcription factor fused leaves1 (ZmFDL1) and influenced by ABA.
Overexpression of Mdm36 reveals Num1 foci that mediate dynein-dependent microtubule sliding in budding yeast
Authors: Omer Safia , Brock Katia , Beckford John , Lee Wei-Lih 
Published: March 2020

ABSTRACTCurrent model for spindle positioning requires attachment of the microtubule (MT) motor cytoplasmic dynein to the cell cortex, where it generates pulling force on astral MTs to effect spindle displacement. How dynein is anchored by cortical attachment machinery to generate large spindle-pulling forces remains unclear. Here, we show that cortical clustering of Num1, the yeast dynein attachment molecule, is limited by Mdm36. Overexpression of Mdm36 results in an overall enhancement of Num1 clustering but reveals a population of dim Num1 clusters that mediate dynein-anchoring at the cell cortex. Direct imaging shows that bud-localized, dim Num1 clusters containing only ∼6 copies of Num1 molecules mediate dynein-dependent spindle pulling via lateral MT sliding mechanism. Mutations affecting Num1 clustering interfere with mitochondrial tethering but not dynein-based spindle-pulling function of Num1. We propose that formation of small ensembles of attachment molecules is sufficient for dynein anchorage and cortical generation of large spindle-pulling force.
Loss of mutant TP53 does not impair the sustained proliferation, survival or metastasis of diverse cancer cells
Authors: Wang Zilu , Vaillant François , Chang Catherine , Riffkin Chris , Lieschke Elizabeth , Diepstraten Sarah , Huang David CS , Visvader Jane E , Herold Marco J , Kelly Gemma L , Strasser Andreas 
Published: March 2020

AbstractThe tumour suppressorTP53is the most frequently mutated gene in human cancer and these aberrations confer poor chemotherapeutic responses1-3. Point mutations typically cluster in the DNA binding domain, with certain ‘hot-spot’ residues disproportionally represented1-4These mutations abrogate binding of the TP53 transcription factor to DNA and thereby prevent upregulation of genes critical for tumour suppression (loss-of-function)1-3. Mutant TP53 is reported to additionally contribute to tumour development, sustained growth and metastasis not only through dominant-negative effects on wild-type TP535but also through neomorphic gain-of-function (GOF) activities6. Understanding the contributions of these postulated attributes of mutant TP53 to the development and expansion of tumours will facilitate the design of rational therapeutic strategies. Here we used CRISPR/CAS9 to delete mutantTP53in a panel of diverse human cancer cell lines. The loss of mutantTP53expression had no impact on the survival, proliferative capacity or metabolic state of the tumour cells, nor did it sensitise them to cellular stresses and chemotherapeutic agents. These data suggest that putative GOF effects of mutant TP53 are not universally required for the sustained survival and proliferation of fully malignant cells. Therefore, therapeutic approaches that abrogate expression or function of mutant TP53 would not be expected to have substantial impact.
Improving a probabilistic cytoarchitectonic atlas of auditory cortex using a novel method for inter-individual alignment
Authors: Gulban Omer Faruk , Goebel Rainer , Moerel Michelle , Zachlod Daniel , Mohlberg Hartmut , Amunts Katrin , De Martino Federico 
Published: March 2020

AbstractThe human superior temporal plane, the site of the auditory cortex, displays a high inter-individual macro-anatomical variation. This questions the validity of curvature based alignment (CBA) methods for in vivo imaging data. Here, we have addressed this issue by developing CBA+, which is a cortical surface registration method that uses prior macro-anatomical knowledge. We validate this method by using cyto-architectonic areas on ten individual brains (which we make publicly available). Compared to volumetric and standard surface registration, CBA+ results in a more accurate cyto-architectonic auditory atlas. The improved correspondence of micro-anatomy following the improved alignment of macro-anatomy validates the superiority of CBA+ compared to CBA. In addition, we use CBA+ to align in vivo and post mortem data. This allows projection of functional and anatomical information collected in vivo onto the cyto-architectonic areas, which has potential to contribute to ongoing debate on the parcellation of the human auditory cortex.
Distinct ensembles in the noradrenergic locus coeruleus evoke diverse cortical states
Authors: Noei Shahryar , Zouridis Ioannis S. , Logothetis Nikos K. , Panzeri Stefano , Totah Nelson K. 
Published: March 2020

AbstractThe noradrenergic locus coeruleus (LC) is a crucial controller of brain and behavioral states. Activating LC neurons synchronouslyen masseby electrical or optogenetic stimulation promotes a stereotypical “activated” high-frequency cortical state. However, it has been recently reported that spontaneous LC cell-pairs have sparse yet structured time-averaged cross-correlations, which is unlike the high synchrony ofen masseneuronal stimulation. This suggests the untested possibility that LC population activity may be made of distinct multi-cell ensembles each with unique temporal evolution of activity. We used non-negative matrix factorization (NMF) to analyze large populations of LC single units simultaneously recorded in the rat LC. Synthetic spike train simulations showed that NMF, unlike the traditional time-averaged pairwise correlations, detects both the precise neuronal composition and the activation time courses of each ensemble. NMF identified the existence of robust ensembles of spontaneously co-active LC neurons. Since LC neurons selectively project to specific forebrain regions, we hypothesized that individual LC ensembles produce different cortical states. To test this hypothesis, we triggered local field potentials (LFP) in cortical area 24a on the activation of distinct LC ensembles. We found four cortical states, each with different spectro-temporal LFP characteristics, that were robust across sessions and animals. While some LC ensembles triggered the activated state, others were associated with a beta oscillation-specific state or a reduced high frequency oscillation state. Thus – in contrast to the stereotypical “activated” brain state evoked byen masseLC stimulation – spontaneous activation of distinct LC ensembles can control a multitude of cortical states.
On the accuracy of molecular simulation-based predictions of koffvalues: a Metadynamics study
Authors: Capelli Riccardo , Lyu Wenping , Bolnykh Viacheslav , Meloni Simone , Haugaard Olsen Jógvan Magnus , Rothlisberger Ursula , Parrinello Michele , Carloni Paolo 
Published: March 2020

AbstractMolecular simulations have made great progresses in predictingkoffvalues—the kinetic constant of drug unbinding, a key parameter for modern pharmacology—yet computed values under- or over-estimate experimental data in a system- and/or technique-dependent way. In an effort at gaining insights on this issue, here we used an established method to calculatekoffvalues—frequency-adaptive metadynamics with force field— and a subsequent QM/MM descriptions of the interactions. First, using force field-based metadynamics, we calculatekoffof the Positron Emission Tomography (PET) ligand iperoxo targeting the human muscarinic acetylcholine receptor M2. In line with previously performedin silicostudies, the prediction (3.7 ± 0.7 ⋅ 10−4s−1) turned out to differ significantly from the experimentally measured value (1.0 ± 0.2 ⋅ 10−2s−1). Next, we use DFT-based QM/MM simulations to show that this discrepancy arises from erroneous force field energetics at the transition state. It turns out that this discrepancy is partly caused by lack of electronic polarization and/or charge transfer in commonly employed force field. We expect these issues to arise also in other systems where charged portions of the system play a pivotal role, such as protein- or DNA-protein complexes.Graphical TOC Entry
Illuminating host-mycobacterial interactions with functional genomic screening to inhibit mycobacterial pathogenesis
Authors: Lai Yong , Babunovic Gregory H. , Cui Liang , Dedon Peter C. , Doench John G. , Fortune Sarah M. , Lu Timothy K. 
Published: March 2020

SUMMARYExisting antibiotics are inadequate to defeat tuberculosis (TB), a leading cause of death worldwide. We sought potential targets for host-directed therapies (HDTs) by investigating the host immune response to mycobacterial infection. We used CRISPR/Cas9-mediated high-throughput genetic screens to identify perturbations that improve the survival of human phagocytic cells infected withMycobacterium bovisBCG (Bacillus Calmette-Guérin), as a proxy forMycobacterium tuberculosis(Mtb). Many of these perturbations constrained the growth of intracellular mycobacteria. We identified over 100 genes associated with diverse biological pathways as potential HDT targets. We validated key components of the type I interferon and aryl hydrocarbon receptor signaling pathways that respond to the small-molecule inhibitors cerdulatinib and CH223191, respectively; these inhibitors enhanced human macrophage survival and limited the intracellular growth of Mtb. Thus, high-throughput functional genomic screens can elucidate highly complex host-pathogen interactions and serve to identify HDTs with the potential to improve TB treatment.
Prediction and discrimination of skeletal muscle function by bioelectrical impedance vector analysis using a standing impedance analyzer in healthy Taiwanese adults
Authors: Lee Li-Wen , Lu Hsueh-Kuan , Chen Yu-Yawn , Lai Chung-Liang , Chu Lee-Ping , Hsieh Meng-Che , Hsieh Kuen-Chang 
Published: March 2020

AbstractBackgroundBioelectrical impedance vector analysis (BIVA) has been used for prediction of muscle performance. However, little is known about BIVA in Asian adults, and even less is known about using standing BIVA devices. Standing impedance analyzer allows quicker and more convenient way to gather data than conventional supine analyzer and is more suitable for clinical practice. This study aimed to investigate the relations between muscle function and BIVA parameters measured with a standing impedance analyzer in healthy Taiwanese adults.MethodsA total of 406 healthy subjects (age 34.5 ± 17.3 years, body mass index 24.1 ± 4.1 kg/m2) were recruited for BIVA and handgrip strength (HGS) measurements. Impedance parameters, including resistance (R) and reactance (Xc), were measured and normalized to body size by dividing by height (H). The resulting phase angle (PhA) was calculated. HGS in the dominant, left, and right hands were referred to as HGSDH, HGSLH, and HGSRH, respectively. All subjects were divided into 5 grades according to HGS.ResultsMuscle strength in the dominant, right, and left arms was correlated with variables in the order of sex, weight, age, height, Xc/H, and R/H (all, p < 0.001). Using all 6 variables, the determination coefficients were 0.792, 0.782, and 0.745, respectively, whereas the standard errors of estimates were 56.89, 58.01, and 56.67 N for HGSDH, HGSLH, and HGSRH, respectively. HGS was positively correlated with PhA, and negatively correlated with Xc/H and R/H.ConclusionsBIVA parameters measured with a standing impedance analyzer and anthropometric variables can predict and discriminate muscle function with good performance in healthy Asian adults.
A network model of the barrel cortex combined with a differentiator detector reproduces features of the behavioral response to single-neuron stimulation
Authors: Bernardi Davide , Doron Guy , Brecht Michael , Lindner Benjamin 
Published: March 2020

AbstractThe stimulation of a single neuron in the rat somatosensory cortex can elicit a behavioral response. The probability of a behavioral response does not depend appreciably on the duration or intensity of a constant stimulation, whereas the response probability increases significantly upon injection of an irregular current. Biological mechanisms that can potentially suppress a constant input signal are present in the dynamics of both neurons and synapses and seem ideal candidates to explain these experimental findings. Here, we study a large network of integrate-and-fire neurons with several salient features of neuronal populations in the rat barrel cortex. The model includes cellular spike-frequency adaptation, experimentally constrained numbers and types of chemical synapses endowed with short-term plasticity, and gap junctions. Numerical simulations of this model indicate that cellular and synaptic adaptation mechanisms alone may not be sufficient to account for the experimental results if the local network activity is read out by an integrator. However, a differentiator circuit can detect the single-cell stimulation with a reliability that barely depends on the length or intensity of the stimulus, but that increases when an irregular signal is used. This finding is in accordance with the experimental results obtained for the stimulation of a regularly-spiking excitatory cell.Author summaryIt is widely assumed that only a large group of neurons can encode a stimulus or control behavior. This tenet of neuroscience has been challenged by experiments in which stimulating a single cortical neuron has had a measurable effect on an animal’s behavior. Recently, theoretical studies have explored how a single-neuron stimulation could be detected in a large recurrent network. However, these studies missed essential biological mechanisms of cortical networks and are unable to explain more recent experiments in the barrel cortex. Here, to describe the stimulated brain area, we propose and study a network model endowed with many important biological features of the barrel cortex. Importantly, we also investigate different readout mechanisms, i.e. ways in which the stimulation effects can propagate to other brain areas. We show that a readout network which tracks rapid variations in the local network activity is in agreement with the experiments. Our model demonstrates a possible mechanism for how the stimulation of a single neuron translates into a signal at the population level, which is taken as a proxy of the animal’s response. Our results illustrate the power of spiking neural networks to properly describe the effects of a single neuron’s activity.
UV radiation increases flavonoid protection but decreased reproduction inSilene littorea
Authors: Del Valle J. C. , Buide M. L. , Whittall J. B. , Valladares F. , Narbona E. 
Published: March 2020

AbstractPlants respond to changes in ultraviolet (UV) radiation via morphological and physiological changes. Among the variety of plant UV-responses, the synthesis of UV-absorbing flavonoids constitutes an effective non-enzymatic mechanism to mitigate photoinhibitory and photooxidative damage caused by UV stress, either reducing the penetration of incident UV radiation or acting as quenchers of reactive oxygen species (ROS). In this study, we designed a UV-exclusion experiment to investigate the effects of UV radiation inSilene littorea. We spectrophotometrically quantified concentrations of both anthocyanins and non-anthocyanin flavonoids (flavones) in petals, calyces, leaves and stems. Furthermore, we analyzed the UV effect on the photosynthetic activity in hours of maximum solar radiation and we tested the impact of UV radiation on male and female reproductive performance. We found that anthocyanin concentrations showed a significant decrease of about 20% with UV-exclusion in petals and stems, and 30% in calyces. Flavone concentrations showed a significant reduction of approximately 25% in calyces and stems, and 12% in leaves. Photochemical efficiency of plants grown under UV stress decreased sharply at maximum light stress, but their ability for recovery after light-stress was not affected. In addition, exposure to UV radiation does not seem to affect ovule production or seed set, but decreases the total seed production per plant and pollen production by 69% and 31%, respectively. Our results demonstrate that UV radiation produced opposite effects on flavonoid accumulation and reproduction inS. littorea. UV stress increased flavonoid concentrations, suggesting a photoprotective role of flavonoids against UV radiation, but had negative consequences for reproduction. We propose that this trade-off helps this species to occupy exposed habitats with high UV radiation.
The Regulation of Developmental Diapause is Coordinated with Molting and Olfaction
Authors: Carstensen Heather R. , Villalon Reinard M. , Vertiz Johnny , Banerjee Navonil , Hallem Elissa A. , Hong Ray L. 
Published: March 2020

AbstractDevelopmental and behavioral plasticity allow animals to prioritize alternative genetic programs during fluctuating environments. Behavioral remodeling may be acute in animals that interact with host organisms, since reproductive adults and the developmentally arrested larvae often have different ethological needs for chemical stimuli. To understand the genes that coordinate development and behavior, we used the nematode modelPristionchus pacificusto characterize mutants that inappropriately enter developmental diapause to become dauer larvae (Daf-c). We found several key olfactory differences betweenP. pacificusandC. elegansDaf-c dauers. In addition, the twoP. pacificusDaf-c alleles disrupt steroid synthesis required for proper regulation of the conserved canonical steroid hormone receptor DAF-12, whose dauer-constitutive and cuticle exsheathment phenotypes can be rescued by the feeding of Δ7-dafachronic acid. One allele,csu60, has a deletion in the sole HydroxySteroid Dehydrogenase (HSD) inP. pacificus.Bothhsd-2(csu60)adults and dauers show enhanced attraction to a beetle pheromone, possibly due to the heterochronic activation of dauer-specific neuronal development in the adults. Surprisingly, this enhanced odor attraction acts independently ofdaf-12, revealing unexpected targets of steroid hormones regulating ecdysis and olfaction inP. pacificus.Author SummaryThe remarkable evolutionary success of nematodes can be attributed to their dispersal ability as stress-resistant dauer larvae and the equivalent parasitic infective larvae. The decision to enter dauer development is regulated by a conserved steroid hormone receptor that receives multiple external and internal cues, though the extent in which these cues also coordinate other physiological and behavioral processes is not well understood in divergent species. We used the insect-associated nematodePristionchus pacificusto genetically dissect two mutants that form dauers inappropriately, and found that one mutation in a steroidogenic enzyme,Ppa-hsd-2, is predicted to abolish the biosynthesis of the hormones needed to negatively regulate dauer entry when food is available. Unexpectedly,Ppa-HSD-2 is also required to properly complete the dauer larval molt, known as exsheathment, as well as to confer differences in adult versus dauer larvae chemotaxis behavior towards a host pheromone. Given that dauers are the host-seeking stage of parasitic nematodes, hormonal disruption represents a tenable target for biological control.
Criticality in the conformational phase transition among self-similar groups in intrinsically disordered proteins: probed by salt-bridge dynamics
Authors: Bandyopadhyay Abhirup , Basu Sankar 
Published: March 2020

AbstractIntrinsically disordered proteins (IDP) serve as one of the key components in the global proteome. In contrast to the dominant class of cytosolic globular proteins, they harbor an enormous amount of physical flexibility and structural plasticity enforcing them to be retained in conformational ensembles rather than well defined stable folds. Previous studies in an aligned direction have revealed the importance of transient dynamical phenomena like that of saltbridge formation in IDPs to support their physical flexibility and have further highlighted their functional relevance. For this characteristic flexibility, IDPs remain amenable and accessible to different ordered binding partners, supporting their potential multi-functionality. The current study further addresses this complex structure-functional interplay in IDPs using phase transition dynamics to conceptualize the underlying (avalanche type) mechanism of their being distributed across and hopping around degenerate structural states (conformational ensembles). For this purpose, extensive molecular dynamics simulations have been done and the data analyzed from a statistical physics perspective. Investigation of the plausible scope ‘selforganized criticality’ (SOC) to fit into the complex dynamics of IDPs was found to be assertive, relating the conformational degeneracy of these proteins to their multi-functionality. In accordance with the transient nature of ‘salt-bridge dynamics’, the study further uses it as a probe to explain the structural basis of the proposed criticality in the conformational phase transition among self-similar groups in IDPs. The analysis reveal scale-invariant self-similar fractal geometries in structural conformations of different IDPs. Also, as discussed in the conclusion, the study has the potential to benefit structural tinkering of bio-medically relevant IDPs in the design of biotherapeutics against them.