bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seasonal variation of fermentation rate inSaccharomyces spp. (Ascomycota)?
Authors: Tiefenbrunner Dagmar , Gangl Helmut , Lopandic Ksenija , Tiefenbrunner Wolfgang 
Published: March 2018

AbstractYeast species of the genusSaccharomycesshow some reaction to visible light – although they lack photo pigments and the typical clock genes of fungi – that can be explained by damage of the cytochrome electron transport chain of the mitochondria. Evidence for a circadian clock, entrainable by cyclic environmental stimuli, exists for periodic changing temperature and light as zeitgeber. Whether seasonality follows from the existence of a circadian clock – which is a necessary requirement for annual rhythms – remains unknown.Due to an accidental observation, we were able to show that fermentation taking place in complete darkness and at constant temperature is influenced in some yeast strains by the history of the inoculum culture. Using yeast cultures growing on agar plates and exposed to diffuse daylight for three weeks either in March or in May as inoculum, leads to significantly different fermentation rates in the inoculated grape juice in both months: rates are higher in March when day length is shorter than in May. In must inoculated with cultures that grew in darkness or daylight, respectively, higher fermentation rates occur by the former. Other yeast strains react to artificial white light in the same way.We used strains ofS. cerevisiae, S. eubayanus, S. kudriavzevii, S. uvarumand furthermore hybrid strains of two or even three of these species. The most pronounced reaction to daylight was shown by theS. eubayanusxS. uvarumxS. cerevisiaehybrid, followed byS. cerevisiaexS. kudriavzeviihybrids,S. eubayanusandS. cerevisiae. S. uvarumwas sensitive to artificial white light.These observations can hardly be explained by some kind of photo damage because they base on an effect that persists through many cell division cycles after yeasts were exposed to light. If it really represents seasonality epigenetic memory is likely involved, since fermentation lasts for many days and yeast generations. If the existence of a circadian clock and seasonal behaviour inSaccharomycesis confirmed these yeasts could become an important tool in basic research concerning epigenetic memory.
Muscarinic receptors regulate auditory and prefrontal cortical communication during auditory processing
Authors: James Nicholas M. , Gritton Howard J. , Kopell Nancy , Sen Kamal , Han Xue 
Published: March 2018

AbstractMuch of our understanding about how acetylcholine modulates prefrontal cortical (PFC) networks comes from behavioral experiments that examine cortical dynamics during highly attentive states. However, much less is known about how PFC is recruited during passive sensory processing and how acetylcholine may regulate connectivity between cortical areas outside of task performance. To investigate the involvement of PFC and cholinergic neuromodulation in passive auditory processing, we performed simultaneous recordings in the auditory cortex (AC) and PFC in awake head fixed mice presented with a white noise auditory stimulus in the presence or absence of local cholinergic antagonists in AC. We found that a subset of PFC neurons were strongly driven by auditory stimuli even when the stimulus had no associative meaning, suggesting PFC monitors stimuli under passive conditions. We also found that cholinergic signaling in AC shapes the strength of auditory driven response in PFC, by modulating the intra-cortical sensory response through muscarinic interactions in AC. Taken together, these findings provide novel evidence that cholinergic mechanisms have a continuous role in cortical gating through muscarinic receptors during passive processing and expand traditional views of prefrontal cortical function and the contributions of cholinergic modulation in sensory gating.HighlightsPrefrontal cortex actively monitors non-associative stimuli under passive conditionsAcetylcholine facilitates cortical signaling even outside of attentional contextsLocal scopolamine infusion reduced intracortical signaling and impaired cortical gatingmAChR have an ongoing role in sound processing
The draft genome of the invasive walking stick,Medauroidea extradendata, reveals extensive lineage-specific gene family expansions of cell wall degrading enzymes in Phasmatodea
Authors: Brand Philipp , Lin Wei , Johnson Brian R. 
Published: March 2018

AbstractPlant cell wall components are the most abundant macromolecules on Earth. The study of the breakdown of these molecules is thus a central question in biology. Surprisingly, plant cell wall breakdown by herbivores is relatively poorly understood, as nearly all early work focused on the mechanisms used by symbiotic microbes to breakdown plant cell walls in insects such as termites. Recently, however, it has been shown that many organisms make endogenous cellulases. Insects, and other arthropods, in particular have been shown to express a variety of plant cell wall degrading enzymes in many gene families with the ability to break down all the major components of the plant cell wall. Here we report the genome of a walking stick,Medauroidea extradentata, an obligate herbivore that makes uses of endogenously produced plant cell wall degrading enzymes. We present a draft of the 3.3Gbp genome along with an official gene set that contains a diversity of plant cell wall degrading enzymes. We show that at least one of the major families of plant cell wall degrading enzymes, the pectinases, have undergone a striking lineage-specific gene family expansion in the Phasmatodea. This genome will be a useful resource for comparative evolutionary studies with herbivores in many other clades and will help elucidate the mechanisms by which metazoans breakdown plant cell wall components.Data availabilityTheMedauroidea extradentatagenome assembly, Med v1.0, is available for download via NCBI (Bioproject: PRJNA369247). The genome, annotation files, and official gene set Mext_OGS_v1.0 are also available at the i5k NAL workspace (https://i5k.nal.usda.gov/medauroidea-extradentata) and at github (https://github.com/pbrec/medauroidea_genome_resources). The genomic raw reads are available via NCBI SRA: SRR6383867 and the raw transcriptomic reads are available at NCBI SRA: SRR6383868, SRR6383869.
Retinal Ganglion Cell Axon Sorting at the Optic Chiasm Requires Dystroglycan
Authors: Clements Reena , Wright Kevin M. 
Published: March 2018

AbstractIn the developing visual system, retinal ganglion cell (RGC) axons project from the retina to several distal retinorecipient regions in the brain. Several molecules have been implicated in guiding RGC axons in vivo, but the role of extracellular matrix molecules in this process remains poorly understood. Dystroglycan is a laminin-binding transmembrane protein important for formation and maintenance of the extracellular matrix and basement membranes and has previously been implicated in axon guidance in the developing spinal cord. Using two genetic models of functional dystroglycan loss, we show that dystroglycan is necessary for correct sorting of contralateral and ipsilateral RGC axons at the optic chiasm. Missorted axons still target retinorecipient brain regions and persist in adult mice, even after axon pruning is complete. Our results highlight the importance of the extracellular matrix for axon sorting at an intermediate choice point in the developing visual circuit.Summary StatementAbnormal retinal ganglion cell axon sorting in the optic chiasm in the absence of functional dystroglycan results in profound defects in retinorecipient innervation.
A statistical framework for cross-tissue transcriptome-wide association analysis
Authors: Hu Yiming , Li Mo , Lu Qiongshi , Weng Haoyi , Wang Jiawei , Zekavat Seyedeh M. , Yu Zhaolong , Li Boyang , Muchnik Sydney , Shi Yu , Kunkle Brian W. , Mukherjee Shubhabrata , Natarajan Pradeep , Naj Adam , Kuzma Amanda , Zhao Yi , Crane Paul K. ,   Alzheimer’s Disease Genetics Consortium, Zhao Hongyu 
Published: March 2018

AbstractTranscriptome-wide association analysis is a powerful approach to studying the genetic architecture of complex traits. A key component of this approach is to build a model to predict (impute) gene expression levels from genotypes from samples with matched genotypes and expression levels in a specific tissue. However, it is challenging to develop robust and accurate imputation models with limited sample sizes for any single tissue. Here, we first introduce a multi-task learning approach to jointly impute gene expression in 44 human tissues. Compared with single-tissue methods, our approach achieved an average 39% improvement in imputation accuracy and generated effective imputation models for an average 120% (range 13%-339%) more genes in each tissue. We then describe a summary statistic-based testing framework that combines multiple single-tissue associations into a single powerful metric to quantify overall gene-trait association at the organism level. When our method, called UTMOST, was applied to analyze genome wide association results for 50 complex traits (Ntotal=4.5 million), we were able to identify considerably more genes in tissues enriched for trait heritability, and cross-tissue analysis significantly outperformed single-tissue strategies (p=1.7e-8). Finally, we performed a cross-tissue genome-wide association study for late-onset Alzheimer’s disease (LOAD) and replicated our findings in two independent datasets (Ntotal=175,776). In total, we identified 69 significant genes, many of which are novel, leading to novel insights on LOAD etiologies.
Microdeletions excludingYWHAEandPAFAH1B1cause a unique leukoencephalopathy and hypermobility syndrome: Further delineation of the 17p13.3 microdeletion spectrum
Authors: Emrick Lisa T. , Rosenfeld Jill A. , Lalani Seema R. , Jain Mahim , Hunter Jill V. , Nagakura Honey , Immken LaDonna L. , Burrage Lindsay C. , Bacino Carlos A. , Belmont John W. , Lee Brendan 
Published: March 2018

ABSTRACTPurposeBrain malformations are caused by 17p13.3 deletions: lissencephaly with deletions of the larger Miller-Dieker syndrome region or smaller deletions of onlyPAFAH1B1, as well as various abnormalities, including white matter changes, in the distinct syndrome due to deletions includingYWHAEandCRKbut sparingPAFAH1B1.We sought to understand the significance of 17p13.3 deletions between theYWHAE/CRKandPAFAH1B1loci.MethodsWe analyzed the clinical features of five individuals from four families with 17p13.3 deletions between and not includingYWHAE/CRKandPAFAH1B1identified among individuals undergoing clinical chromosomal microarray testing.ResultsFour individuals from three families have multi-focal white matter lesions and hypermobile joints, while a fifth had a normal MRI. A combination of our patients and a review of those in the literature with white matter changes and deletions in this chromosomal region narrows the overlapping region for this brain phenotype to ∼345 kb, including 11 RefSeq genes, withRTN4RL1haploinsufficiency as the best candidate for causing this.ConclusionWhile previous literature has hypothesized dysmorphic features and white matter changes related toYWHAE, our cohort contributes evidence to the presence of additional genes within 17p13.3 required for proper brain development.
Linear motor driven-rotary motion of a membrane-permeabilized ghost in Mycoplasma mobile
Authors: Kinosita Yoshiaki , Miyata Makoto , Nishizaka Takayuki 
Published: March 2018

AbstractMycoplasma mobile exhibits a smooth gliding movement as does its membrane-permeabilized ghost model. This exceptionally prominent experimental system has allowed us to conclude that the energy source for M. mobile motility is adenosine triphosphate (ATP), and the gliding is largely comprised of repetitions of unitary steps of about 70 nm. In the present study, we show a new motility mode, in which the ghost model prepared with a high concentration of detergent exhibits directed rotational motions with a constant speed. With a rotational speed and viscous friction of a single ghost, the torque was estimated to be ∼30 pN nm at saturated [ATP]s. Although the origin of the rotation has not been conclusively settled, we found that rotary ghosts treated with sialyllactose, the binding target for leg proteins, were stopped. This result suggested that biomolecules embedded on the cell membrane nonspecifically attaches to the glass and works as a flexible pivot point, and the linear motion of the leg is a driving force for a rotary motion. This simple geometry exemplifies the new mechanism, by which the movement of a linear motor is efficiently converted to a constant rotation of the object on a micrometer scale.
Dynamics of human protein kinases linked to drug selectivity
Authors: Pitsawong Warintra , Buosi Vanessa , Otten Renee , Agafonov Roman V. , Zorba Adelajda , Kern Nadja , Kutter Steffen , Kern Gunther , Pádua Ricardo A. P. , Meniche Xavier , Kern Dorothee 
Published: March 2018

AbstractProtein kinases are major drug targets, but the development of highly-selective inhibitors has been challenging due to the similarity of their active sites. The observation of distinct structural states of the fully-conserved Asp-Phe-Gly (DFG) loop has put the concept of conformational selection for the DFG-state at the center of kinase drug discovery. Recently, it was shown that Gleevec selectivity for the Tyr-kinases Abl was instead rooted in conformational changes after drug binding. Here, we investigate whether protein dynamics after binding is a more general paradigm for drug selectivity by characterizing the binding of several approved drugs to the Ser/Thr-kinase Aurora A. Using a combination of biophysical techniques, we propose a universal drug-binding mechanism, that rationalizes selectivity, affinity and long on-target residence time for kinase inhibitors. These new concepts, where protein dynamics in the drug-bound state plays the crucial role, can be applied to inhibitor design of targets outside the kinome.eLife digestThe Ser/Thr kinase Aurora A is an important target for the development of new anticancer therapies. A longstanding question is how to specifically and effectively inhibit only this kinase in a background of over 550 protein kinases with very similar structures. To this end, understanding the inhibition mechanism of Aurora A by different drugs is essential. Here, we characterize the kinetic mechanism of three distinct kinase drugs, Gleevec (Imatinib), Danusertib (PHA739358) and AT9283 (Pyrazol-4-yl Urea) for Aurora A. We show that inhibitor affinities do not rely exclusively on the recognition of a specific conformation of the Asp-Phe-Gly loop of the kinase. Our quantitative kinetics data put forward an opposing mechanism in which a slow conformational change after drug binding (i.e., induced-fit step) dictates drug affinity.
MUTE Directly Orchestrates Cell State Switch and the Single Symmetric Division to Create Stomata
Authors: Han Soon-Ki , Qi Xingyun , Sugihara Kei , Dang Jonathan H. , Endo Takaho A. , Miller Kristen L. , Kim Eun-deok , Miura Takashi , Torii Keiko U. 
Published: March 2018

SUMMARYPrecise cell division control is critical for developmental patterning. For the differentiation of a functional stoma, a cellular valve for efficient gas exchange, the single symmetric division of an immediate precursor is absolutely essential. Yet, the mechanism governing the single division event remains unclear. Here we report the complete inventories of gene expression by the Arabidopsis bHLH protein MUTE, a potent inducer of stomatal differentiation. MUTE switches the gene expression program initiated by its sister bHLH, SPEECHLESS. MUTE directly induces a suite of cell-cycle genes, including CYCD5;1, and their transcriptional repressors, FAMA and FOUR LIPS. The architecture of the regulatory network initiated by MUTE represents an Incoherent Type 1 Feed-Forward Loop. Our mathematical modeling and experimental perturbations support a notion that MUTE orchestrates a transcriptional cascade leading to the tightly-restricted, robust pulse of cell-cycle gene expression, thereby ensuring the single cell division to create functional stomata.HighlightsComplete inventories of gene expression in stomatal differentiation state are elucidatedMUTE switches stomatal patterning program initiated by its sister bHLH, SPEECHLESSMUTE directly induces cell-cycle genes and their direct transcriptional repressorsIncoherent feed-forward loop by MUTE ensures the single division of a stomatal precursor
Open Force Field Consortium: Escaping atom types using direct chemical perception with SMIRNOFF v0.1
Authors: Mobley David L. , Bannan Caitlin C. , Rizzi Andrea , Bayly Christopher I. , Chodera John D. , Lim Victoria T. , Lim Nathan M. , Beauchamp Kyle. A. , Shirts Michael R. , Gilson Michael K. , Eastman Peter K. 
Published: March 2018

AbstractHere, we focus on testing and improving force fields for molecular modeling, which see widespread use in diverse areas of computational chemistry and biomolecular simulation. A key issue affecting the accuracy and transferrability of these force fields is the use of atom typing. Traditional approaches to defining molecular mechanics force fields must encode, within a discrete set of atom types, all information which will ever be needed about the chemical environment; parameters are then assigned by looking up combinations of these atom types in tables. This atom typing approach leads to a wide variety of problems such as inextensible atom-typing machinery, enormous difficulty in expanding parameters encoded by atom types, and unnecessarily proliferation of encoded parameters. Here, we describe a new approach to assigning parameters for molecular mechanics force fields based on the industry standard SMARTS chemical perception language (with extensions to identify specific atoms available in SMIRKS). In this approach, each force field term (bonds, angles, and torsions, and nonbonded interactions) features separate definitions assigned in a hierarchical manner without using atom types. We accomplish this using direct chemical perception, where parameters are assigned directly based on substructure queries operating on the molecule(s) being parameterized, thereby avoiding the intermediate step of assigning atom types — a step which can be considered indirect chemical perception. Direct chemical perception allows for substantial simplification of force fields, as well as additional generality in the substructure queries. This approach is applicable to a wide variety of (bio)molecular systems, and can greatly reduce the number of parameters needed to create a complete force field. Further flexibility can also be gained by allowing force field terms to be interpolated based on the assignment of fractional bond orders via the same procedure used to assign partial charges. As an example of the utility of this approach, we provide a minimalist small molecule force field derived from Merck’s parm@Frosst (an Amber parm99 descendant), in which a parameter definition file only ≈ 300 lines long can parameterize a large and diverse spectrum of pharmaceutically relevant small molecule chemical space. We benchmark this minimalist force field on the FreeSolv small molecule hydration free energy set and calculations of densities and dielectric constants from the ThermoML Archive, demonstrating that it achieves comparable accuracy to the Generalized Amber Force Field (GAFF) that consists of many thousands of parameters.
Developing high performance working through case study evidence
Authors: Grant Kirsteen , Maxwell Gillian A. 
Published: March 2018

Purpose
This paper aims to theoretically proffer and empirically evidence five inter-related high performance working (HPW) groupings of value to practitioners interested in developing HPW in their organizations.

Design/methodology/approach
The empirical research is based on three UK-based qualitative case studies. Data are drawn from nine in-depth interviews with managers (three from each case) and three subsequent focus groups (one in each case). Focus groups comprised six, eight, and four employee (non-manager) interviewees.

Findings
The empirical findings validate the theoretical importance of the five identified HPW groupings. More, they imply a number of relationships within and between the five groupings, confirming the need to view the groupings collectively and dynamically.

Originality/value
The five HPW groupings provide a foundation for further research to closely evaluate the dynamism within and across the groupings. They also offer practical types of human resource interventions and actions for practitioners to evaluate the strengths and weaknesses of HPW in their organizations.
Municipal reaction to functional rescaling in Italy
Authors: Bolgherini Silvia , Casula Mattia , Marotta Mariano 
Published: March 2018

PurposeThe purpose of this paper is to discuss the municipal reaction to a recent rescaling policy in Italy that, since 2010, require to small municipalities to jointly manage their basic tasks (compulsory joint management – CJM) through intermunicipal forms of cooperation. The paper will investigate: how many small municipalities did effectively join their basic tasks; which forms of cooperation did they choose to perform these tasks; and which kind of reaction municipalities enacted toward the national provision.Design/methodology/approachQuantitative data rely on an original database collecting information on all Italian municipalities up to 2015. A qualitative research has also been conducted by submitting a semi-structured questionnaire and interviews to the civil servants in charge of the CJM in each of the 20 Italian regions and to other privileged interlocutors.FindingsItalian municipalities poorly complied with the CJM norm and when they did, they choose the easiest way to do it (using the simplest available intermunicipal cooperation form). Among the explanations for this reaction: the lack of consistency and clear political will of the national policy maker in respect to this norm and the lack of a mind set at the local level oriented to cooperation and networking.Originality/valueThis paper highlights the main patterns of conflict in functional rescaling of small-sized municipalities in Italy, thus providing both fresh new data on this phenomena and useful elements for shaping future policy making on this topic.
Can land value uplift deliver affordable housing? Experiences from England
Authors: Wyatt Peter 
Published: March 2018

Purpose
The theoretical case for land value capture is well-known, but the effectiveness of affordable housing delivery as a capture mechanism is not so well-documented. Building on the earlier theoretical and empirical work of Whitehead (1991, 2007) and Crook and Whitehead (2002), the purpose of this paper is to consider the provision of affordable housing from a land value capture viewpoint, focusing on the process by which the amount of affordable housing is determined between landowners/developers on the one hand and local planning authorities on the other.

Design/methodology/approach
The paper adopts a mixed-mode approach for the data collection. Two surveys of local planning authorities were undertaken, together with a series of case study interviews.

Findings
The paper evaluates whether land value capture has been an effective mechanism for delivering affordable housing by focusing on three principal areas: first, the political agenda in relation to land value capture and the supply of affordable housing; second, the nature and motivation of the stakeholders involved in affordable housing decision-making; and third, the use of economic models as decision tools for determining the amount and type of affordable housing are negotiated.

Originality/value
The research provides some insight into the effectiveness of local authority affordable housing targets as a means of capturing the uplift in land value that results from the grant of planning permission.