bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrospun cellulose acetate/gelatin nanofibrous wound dressing containing berberine for diabetic foot ulcer healing: in vitro and in vivo studies
Authors: Samadian Hadi , Ehterami Arian , Farzamfar Saeed , Vaez Ahmad , Khastar Hossein , Alam Mostafa , Ai Armin , Allahyari Zahra , Salehi Majid 
Published: October 2019

AbstractFunctional dressing with tailored physicochemical and biological properties is vital for diabetic foot ulcer (DFU) treatment. Our main objective in the current study was to fabricate Cellulose Acetate/Gelatin (CA/Gel) electrospun nanofibrous mat loaded with berberine (Beri) as the DFU dressing. The results demonstrated that the diameter of the nanofibers was around 502 nm, the tensile strength, contact angle, porosity, water vapor permeability, and water uptake ratio of CA/Gel nanofibers were around 2.83 MPa, 58.07, 78.17 %, 11.23 mg/cm2 hr, and 12.78 respectively, while these values for CA/Gel/Beri nanofibers were 2.69 ± 0.05 MPa, 56.93 ± 1, 76.17 ± 0.76 %, 10.17 ± 0.21 mg/cm2 hr, 14.37 ± 0.42 respectively. The bacterial evaluations demonstrated that the dressings are an excellent barrier against bacterial penetration with potent antibacterial activity. The animal studies depicted that the collagen density and angiogenesis score in the CA/Gel/Beri treated group were 88.8±6.7 % and 19.8±3.8, respectively. These findings implied that the incorporation of berberine did not compromise the physical properties of dressing, while improving the biological activates. In conclusion, our findings implied that the prepared mat is a proper wound dressing for DFU management and treatment.
PseudomonasmRNA 2.0: Boosting Gene Expression Through Enhanced mRNA Stability and Translational Efficiency
Authors: Neves Dário , Vos Stefan , Blank Lars M. , Ebert Birgitta E. 
Published: October 2019

AbstractHigh gene expression of enzymes partaking in recombinant production pathways is a desirable trait among cell factories belonging to all different kingdoms of life. High enzyme abundance is generally aimed for by utilizing strong promoters, which ramp up gene transcription and mRNA levels. Increased protein abundance can alternatively be achieved by optimizing the expression on the post-transcriptional level. Here, we evaluated protein synthesis with a previously proposed optimized gene expression architecture, in which mRNA stability and translation initiation are modulated by genetic parts such as self-cleaving ribozymes and a bicistronic design, which have initially been described to support the standardization of gene expression. The optimized gene expression architecture was tested inPseudomonas taiwanensisVLB120, a promising, novel microbial cell factory. The expression cassette was employed on a plasmid basis and after single genomic integration. We used three constitutive and two inducible promoters to drive the expression of two fluorescent reporter proteins and a short acetoin biosynthesis pathway. The performance was confronted with that of a traditional expression cassette harboring the same promoter and gene of interest but lacking the genetic parts for increased expression efficiency. The optimized expression cassette granted higher protein abundance independently of the expression basis or promoter used proving its value for applications requiring high protein abundance.
Tissue-autonomous immune response regulates stress signalling during hypertrophy
Authors: Krautz Robert , Khalili Dilan , Theopold Ulrich 
Published: October 2019

AbstractPostmitotic tissues are incapable of replacing damaged cells through proliferation, but need to rely on buffering mechanisms to prevent tissue disintegration. By constitutively activating the Ras/MAPK-pathway viaRasV12-overexpression in the postmitotic salivary glands ofDrosophilalarvae, we overrode the glands adaptability to growth signals, induced hypertrophy and stress accumulation. This allowed us to decipher a novel, spatio-temporally regulated interaction between the JNK-stress response and a genuine tissue-autonomous immune response. Central to this interaction is the direct inhibition of JNK-signalling by the antimicrobial peptide Drosomycin, which blocks programmed cell death and prevents recognition of the stressed tissue by the systemic immune response. While this mechanism might allow growing salivary glands to cope with temporary stress, continuous expression of Drosomycin favors survival of unrestricted, hypertrophicRasV12-glands. Our findings indicate the necessity for refined therapeutic approaches that fundamentally acknowledge detrimental effects that stimulated immune responses have on tissues coping with damage and stress.
The involvement of neuroimmune cells in adipose innervation
Authors: Blaszkiewicz Magdalena , Wood Elizabeth , Koizar Sigi , Willows Jake , Anderson Ryan , Tseng Yu-Hua , Godwin James , Townsend Kristy L. 
Published: October 2019

AbstractBackgroundInnervation of adipose tissue is essential for the proper function of this critical metabolic organ. Numerous surgical and chemical denervation studies have demonstrated how maintenance of brain-adipose communication through both sympathetic efferent and sensory afferent nerves helps regulate adipocyte size, cell number, lipolysis, and ‘browning’ of white adipose tissue. Neurotrophic factors are growth factors that promote neuron survival, regeneration and plasticity, including neurite outgrowth and synapse formation. Peripheral blood immune cells have been shown to be a source of neurotrophic factors in humans and mice. Although a number of immune cells reside in the adipose stromal vascular fraction (SVF), it has remained unclear what roles they play in adipose innervation. We previously demonstrated that adipose immune cells secrete brain derived neurotrophic factor (BDNF).MethodsWe now show that deletion of this neurotrophic factor from the myeloid lineage led to a ‘genetic denervation’ of inguinal subcutaneous white adipose tissue (scWAT), thereby causing decreased energy expenditure, increased adipose mass, and a blunted UCP1 response to cold stimulation.ResultsWe and others have previously shown that noradrenergic stimulation via cold exposure increases adipose innervation in the inguinal depot. Here we have identified a subset of myeloid cells that home to scWAT upon cold exposure and are Ly6C + CCR2 + Cx3CR1 + monocytes/macrophages that express noradrenergic receptors and BDNF.ConclusionsWe propose that these cold induced neuroimmune cells (CINCs) are key players in maintaining adipose innervation as well as promoting adipose nerve remodeling under noradrenergic stimulation, such as cold exposure.
A Normative Bayesian Model of Classification for Agents with Bounded Memory
Authors: Lee Heeseung , Lee Hyang-Jung , Choe Kyoung Whan , Lee Sang-Hun 
Published: October 2019

AbstractClassification, one of the key ingredients for human cognition, entails establishing a criterion that splits a given feature space into mutually exclusive subspaces. In classification tasks performed in daily life, however, a criterion is often not provided explicitly but instead needs to be guessed from past samples of a feature space. For example, we judge today’s temperature to be “cold” or “warm” by implicitly comparing it against a “typical” seasonal temperature. In such situations, establishing an optimal criterion is challenging for cognitive agents with bounded memory because it requires retrieving an entire set of past episodes with precision. As a computational account for how humans carry out this challenging operation, we developed a normative Bayesian model of classification (NBMC), in which Bayesian agents, whose working-memory precision decays as episodes elapse, continuously update their criterion as they perform a binary perceptual classification task on sequentially presented stimuli. We drew a set of specific implications regarding key properties of classification from the NBMC, and demonstrated the correspondence between the NBMC and human observers in classification behavior for each of those implications. Furthermore, in the functional magnetic resonance imaging responses acquired concurrently with behavioral data, we identified an ensemble of brain activities that coherently represent the latent variables, including the inferred criterion, of the NBMC. Given these results, we believe that the NBMC is worth being considered as a useful computational model that guides behavioral and neural studies on perceptual classification, especially for agents with bounded memory representation of past sensory events.Significant StatementAlthough classification—assigning events into mutually exclusive classes—requires a criterion, people often have to perform various classification tasks without explicit criteria. In such situations, forming a criterion based on past experience is quite challenging because people’s memory of past events deteriorates quickly over time. Here, we provided a computational model for how a memory-bounded yet normative agent infers the criterion from past episodes to maximally perform a binary perceptual classification task. This model successfully captured several key properties of human classification behavior, and the neural signals representing its latent variables were identified in the classifying human brains. By offering a rational account for memory-bonded agents’ classification, our model can guide future behavioral and neural studies on perceptual classification.
Stable behavioral and neural responses to thermal stimulation despite large changes in theHydra vulgarisnervous system
Authors: Tzouanas Constantine N. , Kim Soonyoung , Badhiwala Krishna N. , Avants Benjamin W. , Robinson Jacob T. 
Published: October 2019

AbstractMany animals that lose neural tissue due to injury or disease have the ability to maintain their behavioral abilities by regenerating new neurons or reorganizing existing neural circuits. However, most small model organisms used for neuroscience like nematodes and flies lack this high degree of neural plasticity. These animals often show significant behavioral deficits if they lose even a single neuron. Here we show that the small freshwater cnidarianHydra vulgariscan maintain stable sensory motor behaviors even after losing half of the neurons in its body. Specifically, we find that both the behavioral and neural response to a rapid change in temperature is maintained if we make their nervous system roughly 50% smaller by caloric restriction or surgery. These observations suggest thatHydraprovides a rich model for studying how animals maintain stable sensory-motor responses within dynamic neural circuit architectures, and may lead to general principles for neural circuit plasticity and stability.Significance StatementThe ability of the nervous system to restore its function following injury is key to survival for many animals. Understanding this neural plasticity in animals across the phylogenetic tree would help reveal fundamental principles of this important ability. To our knowledge, the discovery of a set of neurons in the jellyfish polypHydra vulgaristhat stably support a response to thermal stimulation is the first demonstration of large-scale neural plasticity in a genetically tractable invertebrate model organism. The small size and transparency ofHydrasuggests that it will be possible to study large-scale neural circuit plasticity in an animal where one can simultaneously image the activity of every neuron.
Hey, look over there: Distraction effects on rapid sequence recall
Authors: Miner Daniel , Tetzlaff Christian 
Published: October 2019

AbstractIn the course of everyday life, the brain must store and recall a huge variety of representations of stimuli which are presented in an ordered or sequential way. The processes by which the ordering of these various things is stored and recalled are moderately well understood. We use here a computational model of a cortex-like recurrent neural network adapted by a multitude of plasticity mechanisms. We first demonstrate the learning of a sequence. Then, we examine the influence of different types of distractors on the network dynamics during the recall of the encoded ordered information being ordered in a sequence. We are able to broadly arrive at two distinct effect-categories for distractors, arrive at a basic understanding of why this is so, and predict what distractors will fall into each category.
Weak Acid Resistance A (WarA), a novel transcription factor required for regulation of weak-acid resistance and spore-spore heterogeneity inAspergillus niger
Authors: Geoghegan Ivey A. , Stratford Malcolm , Bromley Mike , Archer David B. , Avery Simon V. 
Published: October 2019

ABSTRACTPropionic, sorbic and benzoic acids are organic weak acids that are widely used as food preservatives, where they play a critical role in preventing microbial growth. In this study, we uncovered new mechanisms of weak acid resistance in moulds. By screening a library of 401 transcription-factor deletion strains inAspergillus fumigatusfor sorbic acid hypersensitivity, a previously uncharacterised transcription factor was identified, and named as WarA (Weak Acid Resistance A). The orthologous gene in the spoilage mouldAspergillus nigerwas identified and deleted. WarA was required for resistance to a range of weak acids, including sorbic, propionic and benzoic acids. A transcriptomic analysis was performed to characterise genes regulated by WarA during sorbic acid treatment inA. niger. Several genes were significantly upregulated in the wild type compared with a ΔwarAmutant, including genes encoding putative weak acid detoxification enzymes and transporter proteins. Among these was An14g03570, a putative ABC-type transporter which we found to be required for weak acid resistance inA. niger. We also show that An14g03570 is a functional homologue of theSaccharomyces cerevisiaeprotein Pdr12p, and therefore named as PdrA. Lastly, resistance to sorbic acid was found to be highly heterogeneous within genetically-uniform populations of ungerminatedA. nigerconidia, and we demonstrate thatpdrAis a determinant of this heteroresistance. This study has identified novel mechanisms of weak acid resistance inA. nigerwhich could help to inform and improve future food spoilage prevention strategies.IMPORTANCEWeak acids are widely used as food preservatives, as they are very effective at preventing growth of most species of bacteria and fungi. However, some species of moulds can survive and grow in the concentrations of weak acid employed in food and drink products, thereby causing spoilage with resultant risks for food security and health. Current knowledge of weak acid resistance mechanisms in these fungi is limited, especially in comparison to that in yeasts. We characterised gene functions in the spoilage mould speciesAspergillus nigerwhich are important for survival and growth in the presence of weak acid preservatives. Such identification of weak acid resistance mechanisms in spoilage moulds will help to design new strategies to reduce food spoilage in the future.
High-resolution proteomics identifies potential new markers of Zika and dengue infections
Authors: Allgoewer Kristina , Zhao Alice , Maity Shuvadeep , Lashua Lauren , Ramgopal Moti , Balkaran Beni N. , Liu Liyun , Arévalo Maria T. , Ross Ted M. , Choi Hyungwon , Ghedin Elodie , Vogel Christine 
Published: October 2019

AbstractDistinguishing between Zika and dengue virus infections is critical for treatment and anticipation of complications. However, existing biomarkers have high error rates. To identify new potential diagnostic signatures, we used next-generation proteomics to profile 122 serum samples from 62 Zika or dengue patients. We quantified >500 proteins and identified 26 proteins that were significantly differentially expressed. These proteins typically function in infection and wound healing, with several also linked to pregnancy and brain. Integrating machine learning approaches, we used 7 proteins to predict ZIKV infection correctly in 72% of the cases, outperforming other tools. The three most predictive proteins were Platelet Factor 4 Variant 1, Fibrinogen Alpha, and Gelsolin. Finally, we showed that temporal changes in protein signatures from the same patient can disambiguate some diagnoses and serve as indicators for past infections. Taken together, we demonstrate that serum proteomics can be highly valuable to diagnose even challenging samples.
No evidence for a relationship between social closeness and similarity in resting-state functional brain connectivity in schoolchildren
Authors: McNabb Carolyn Beth , Burgess Laura Grace , Fancourt Amy , Mulligan Nancy , FitzGibbon Lily , Riddell Patricia , Murayama Kou 
Published: October 2019

AbstractPrevious research suggests that the proximity of individuals in a social network predicts how similarly their brains respond to naturalistic stimuli. However, the relationship between social connectedness and brain connectivity in the absence of external stimuli has not been examined. To investigate whether neural homophily between friends exists at rest we collected resting-state functional magnetic resonance imaging (fMRI) data from 68 school-aged girls, along with social network information from all pupils in their year groups (total 5,066 social dyads). Participants were asked to rate the amount of time they voluntarily spent with each person in their year group, and directed social network matrices and community structure were then determined from these data. No statistically significant relationships between social distance, community homogeneity and similarity of global-level resting-state connectivity were observed. Nor were we able to predict social distance using a machine learning technique (i.e. elastic net regression based on the local-level similarities in resting-state whole-brain connectivity between participants). Although neural homophily between friends exists when viewing naturalistic stimuli, this finding did not extend to functional connectivity at rest in our population. Instead, resting-state connectivity may be less susceptible to the influences of a person’s social environment.
SPARC: a method to genetically manipulate precise proportions of cells
Authors: Isaacman-Beck Jesse , Paik Kristine C. , Wienecke Carl F. R. , Yang Helen H. , Fisher Yvette E. , Wang Irving E. , Ishida Itzel G. , Maimon Gaby , Wilson Rachel I. , Clandinin Thomas R. 
Published: October 2019

AbstractMany experimental approaches rely on controlling gene expression in select subsets of cells within an individual animal. However, reproducibly targeting transgene expression to specific fractions of a genetically-defined cell-type is challenging. We developedSparsePredictiveActivity throughRecombinaseCompetition (SPARC), a generalizable toolkit that can express any effector in precise proportions of post-mitotic cells inDrosophila. Using this approach, we demonstrate targeted expression of many effectors and apply these tools to calcium imaging of individual neurons and optogenetic manipulation of sparse cell populationsin vivo.
Mechanisms of activation and desensitization of full-length glycine receptor in membranes
Authors: Kumar Arvind , Basak Sandip , Rao Shanlin , Gicheru Yvonne , Mayer Megan L. , Sansom Mark S.P , Chakrapani Sudha 
Published: October 2019

AbstractGlycinergic synapses play a central role in motor control and pain processing in the central nervous system. Glycine receptors (GlyR) are key players in mediating fast inhibitory neurotransmission at these synapses. While previous high-resolution structural studies have provided insights into the molecular architecture of GlyR, several mechanistic questions pertaining to channel function are still unknown. Here, we present Cryo-EM structures of the full-length GlyR protein reconstituted into lipid nanodiscs that are captured in the unliganded (closed) and glycine-bound (open and desensitized) conformations. A comparison of the three states reveals global conformational changes underlying GlyR channel gating. The functional state assignments were validated by molecular dynamics simulations of the structures incorporated in a lipid bilayer. Observed permeation events are in agreement with the anion selectivity of the channel and the reported single-channel conductance of GlyR. These studies establish the structural basis for gating, selectivity, and single-channel conductance of GlyR in a physiological environment.
CAP2 is a novel regulator of Cofilin in synaptic plasticity and Alzheimer’s disease
Authors: Pelucchi Silvia , Vandermeulen Lina , Pizzamiglio Lara , Aksan Bahar , Yan Jing , Konietzny Anja , Bonomi Elisa , Borroni Barbara , Rust Marco , Marino Daniele Di , Mikhaylova Marina , Mauceri Daniela , Antonucci Flavia , Gardoni Fabrizio , Luca Monica Di , Marcello Elena 
Published: October 2019

AbstractCofilin is one of the major regulators of actin dynamics in spines where it is required for structural synaptic plasticity. However, our knowledge of the mechanisms controlling Cofilin activity in spines remains still fragmented. Here, we describe the cyclase-associated protein 2 (CAP2) as a novel master regulator of Cofilin localization in spines. The formation of CAP2 dimers through its Cys32 is important for CAP2 binding to Cofilin and for normal spine actin turnover. The Cys32-dependent CAP2 homodimerization and association to Cofilin are triggered by long-term potentiation (LTP) and are required for LTP-induced Cofilin translocation into spines, spine remodeling and the potentiation of synaptic transmission. This mechanism is specifically affected in the hippocampus, but not in the superior frontal gyrus, of both Alzheimer’s Disease (AD) patients and APP/PS1 mice, where CAP2 is down-regulated and CAP2 dimer synaptic levels are reduced. In AD hippocampi, Cofilin preferentially associates with CAP2 monomer and is aberrantly localized in spines. Taken together, these results provide novel insights into structural plasticity mechanisms that are defective in AD.
Risky drinking and dual diagnosis in older people under a UK community old age psychiatry service
Authors: Rao Rahul 
Published: October 2019

Purpose
The assessment of patterns in risky drinking and its association with dual diagnosis in community services for older people remains under-explored. The paper aims to discuss this issue.

Design/methodology/approach
Drinking risk using the Alcohol Use Disorders Identification Test (AUDIT) and the presence of co-existing mental disorders was examined in 190 people aged 65 and over.

Findings
In total, 24 per cent of drinkers drank above lower risk levels and 22 per cent reported binge drinking over the past 12 months. Those scoring 1 or more on the AUDIT were more likely to be male and to have greater cognitive impairment than non-drinkers and those reporting no past problems with alcohol.

Research limitations/implications
Given the limitations of the Mini Mental State Examination in the detection of alcohol related cognitive impairment (ARCI), the use of other cognitive screening instruments in larger study populations is also warranted.

Practical implications
Greater attention needs to be paid to the assessment of risky drinking in older male drinkers and those with cognitive impairment.

Originality/value
There is considerable scope for the routine detection of cognitive impairment and dementia in older people with alcohol use within mainstream mental health services, particularly in those with binge drinking. As ARCI is associated with loss of function and independence, early detection and intervention can improve health and social outcomes.