bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA regulation of CTP synthase and cytoophidium inDrosophila melanogaster
Authors: Dzaki Najat , Kan Woo Wai , Azzam Ghows
Published: August 2018

CTPsyn is a crucial metabolic enzyme which synthesizes CTP molecules through thede novoor salvage pathway. It has the extraordinary ability to compartmentalize into filaments termed cytoophidia. Although this property is retained amongst orthologues, and cytoophidia are therefore found across kingdoms, the mechanisms behind their formation remain unknown. Micro-RNAs (miRNAs) are single-stranded RNA with length of 20 – 22 nucleotides, capable of exerting mRNA silencing and degradation as a form of regulation.D. melanogasteritself has a high total gene count to miRNA gene number ratio, alluding to the possibility thatCTPsynmay too come under the regulatory effects of these small RNAs. A thorough miRNA overexpression involving 123 UAS-miRNA lines, followed by staining of ovarian cytoophidiadme-egg chambers, revealed a small group of candidates which confer either a lengthening or truncating effect on the structure. Prime candidates are identified on the basis of consistency. MiR-975 and miR-1014 are both cytoophidia-elongating, whereas miR-190 and miR-932 are cytoophidia-shortening. Though target prediction shows that miR-975 and miR-932 do indeed have binding sites onCTPsynmRNA,in vitroassays instead revealed that none of the four candidates may actually do so. This suggests that the effects asserted by overexpressed miRNAs indirectly reach CTPsyn and its cytoophidia through the actions of middling elements.In silicotarget prediction and qPCR quantification indicated that, at least for miR-932 and miR-1014, these undetermined elements may be players in fat metabolism. This is the first study to thoroughly investigate miRNAs in connection to CTPsyn expression and activity in any species. The findings presented could serve as a basis for further queries into not only the fundamental aspects of the enzyme’s regulation, but may uncover new facets of closely related pathways as well.
Emergence of Directional Actomyosin Flows from Active Matter Vibrations
Authors: Vogel Sven K. , Wölfer Christian , Ramirez-Diaz Diego A. , Flassig Robert J. , Sundmacher Kai , Schwille Petra
Published: August 2018

Cortical actomyosin flows play pivotal roles in cell motility, cell division and animal morphogenesis. According to many model systems, myosin motor induced local contractions are key for generating cortical flows. However, the original mechanism how large-scale directed flows emerge from local motor activity in an apparently isotropic cortex is unknown. We reconstituted and confined minimal actomyosin cortices to the interfaces of emulsion droplets. The presence of ATP leads to myosin-induced cortical contractions that self-organize into directed flow-like actomyosin motions. By combining our experiments with theory, we found that the large-scale directional motion of actomyosin clusters emerges from individual asymmetric cluster vibrations, caused by intrinsic non-isotropic ATP consumption, in conjunction with spherical confinement. By tracking individual actomyosin clusters, we identified fingerprints of vibrational states as the basis of directed motions. These vibrations may represent a generic key driver of directed actomyosin flows under spatial confinementin vitroand in living systems.
Neuronal constituents and putative interactions within the Drosophila ellipsoid body neuropil
Authors: Omoto Jaison Jiro , Minh Nguyen Bao-Chau , Kandimalla Pratyush , Lovick Jennifer Kelly , Donlea Jeffrey Michael , Hartenstein Volker
Published: August 2018

The central complex (CX) is a midline-situated collection of neuropil compartments in the arthropod central brain, implicated in higher-order processes such as goal-directed navigation. Here, we provide a systematic genetic-neuroanatomical analysis of the ellipsoid body (EB), a compartment which represents a major afferent portal of the Drosophila CX. The neuropil volume of the EB, along with its prominent input compartment, called the bulb, is subdivided into precisely tessellated domains, distinguishable based on intensity of the global marker DN-cadherin. EB tangential elements (so-called ring neurons), most of which are derived from the DALv2 neuroblast lineage, interconnect the bulb and EB domains in a topographically-organized fashion. Using the DN-cadherin domains as a framework, we first characterized the bulb-EB connectivity by Gal4 driver lines expressed in different DALv2 ring neuron (R-neuron) subclasses. We identified 11 subclasses, 6 of which correspond to previously described projection patterns, and 5 novel patterns. These subclasses both spatially (based on EB innervation pattern) and numerically (cell counts) summate to the total EB volume and R-neuron cell number, suggesting that our compilation of R-neuron subclasses approaches completion. EB columnar elements, as well as non-DALv2 derived extrinsic ring neurons (ExR-neurons), were also incorporated into this anatomical framework. Finally, we addressed the connectivity between R-neurons and their targets, using the anterograde trans-synaptic labeling method, trans-Tango. This study demonstrates putative interactions of R-neuron subclasses and reveals general principles of information flow within the EB network. Our work will facilitate the generation and testing of hypotheses regarding circuit interactions within the EB and the rest of the CX.
Protein-Ligand Docking with Protein-based and Ligand-based Structure Activity Relationships
Authors: Fu Darwin Y. , Meiler Jens
Published: August 2018

Protein-small molecule docking programs predict the interaction interface and energy between a given protein target and a small molecule ligand. The accuracy of docking predictions generally improve with the guidance of experimentally derived restraints. One available source of such restraints is structure-activity relationships (SARs). SARs provide information on changes in binding affinity or biological response corresponding to a chemical change in the protein and/or ligand. These chemical changes frequently refer to amino acid mutations on the protein side and functional group modifications on the ligand side. Theoretically, predicted interaction energies should correlate with SARs though in practice, this is challenging due to the difficulties in scoring protein-ligand interactions. We have previously developed RosettaLigandEnsemble (RLE), a protein-ligand docking method that simultaneously docks a congeneric ligand series to a single protein target. RLE is capable of identifying native-like binding modes for a ligand series that match the available ligand SARs. This work in progress reports on the extension of RLE to factor in SARs derived from protein mutagenesis data. The new method, ProteinLigEnsemble (PLE), is also part of the Rosetta Biomolecular Modeling Suite available at https://www.rosettacommons.org/. We have also developed protein ensemble docking features that allow for docking or screening against multiple receptor variants at the same time. We have included a proof of concept study and a tutorial for interested users.
Challenge data set for macromolecular multi-microcrystallography
Authors: Holton James M.
Published: August 2018

A synthetic data set demonstrating a particularly challenging case of indexing ambiguity in the context of radiation damage was generated in order to serve as a standard benchmark and reference point for the ongoing development of new methods and new approaches to solving this problem. Of the 100 short wedges of data only the first 71 are currently necessary to solve the structure by “cheating”, or using the correct reference structure as a guide. The total wall-clock time and number of wedges required to solve the structure without cheating is proposed as a metric for the efficacy and efficiency of a given multi-crystal automation pipeline.

Synopsis

A synthetic dataset demonstrating the challenges of combining multiple data sets with indexing ambiguity in the context of heavy radiation damage in multi-crystal macromolecular crystallography was generated and described, and the problems encountered using contemporary data processing programs were summarized.
Xolotl: An Intuitive and Approachable Neuron and Network Simulator for Research and Teaching
Authors: Gorur-Shandilya Srinivas , Hoyland Alec , Marder Eve
Published: August 2018

Conductance-based models of neurons are used extensively in computational neuroscience. Working with these models can be challenging due to their high dimensionality and large number of parameters. Here, we present a neuron and network simulator built on a novel automatic type system that binds object-oriented code written in C++ to objects in MATLAB. Our approach builds on the tradition of uniting the speed of languages like C++ with the ease-of-use and feature-set of scientific programming languages like MATLAB. Xolotl allows for the creation and manipulation of hierarchical models with components that are named and searchable, permitting intuitive high-level programmatic control over all parts of the model. The simulator’s architecture allows for the interactive manipulation of any parameter in any model, and for visualizing the effects of changing that parameter immediately. Xolotl is fully featured with hundreds of ion channel models from the electrophysiological literature, and can be extended to include arbitrary conductances, synapses, and mechanisms. Several core features like bookmarking of parameters and automatic hashing of source code facilitate reproducible and auditable research. Its ease of use and rich visualization capabilities make it an attractive option in teaching environments. Finally, xolotl is written in a modular fashion, includes detailed tutorials and worked examples, and is freely available at https://github.com/sg-s/xolotl, enabling seamless integration into the workflows of other researchers.
Centromeric CENP-A loading requires accurate mitotic timing, which is linked to checkpoint proteins
Authors: Pauleau Anne Laure , Bergner Andrea , Kajtez Janko , Erhardt Sylvia
Published: August 2018

A defining feature of centromeres is the presence of the histone H3 variant CENP-A that replaces H3 in a subset of centromeric nucleosomes. InDrosophilacultured cells CENP-A deposition at centromeres takes place during the metaphase stage of the cell cycle and strictly depends on the presence of its specific chaperone CAL1. How CENP-A loading is restricted to mitosis is unknown. We found that overexpression of CAL1 is associated with increased CENP-A levels at centromeres and completely uncouples CENP-A loading from mitosis. Moreover, CENP-A levels inversely correlate with mitosis duration. We found that CAL1 interacts with the spindle assembly checkpoint protein and RZZ complex component Zw10 and thus constitutes the anchor for the recruitment of RZZ. Therefore, CAL1 controls CENP-A incorporation at centromeres both quantitatively and temporally, connecting it to the spindle assembly checkpoint to ensure mitotic fidelity.
Triggering visually-guided behavior by holographic activation of pattern completion neurons in cortical ensembles
Authors: Carrillo-Reid Luis , Han Shuting , Yang Weijian , Akrouh Alejandro , Yuste Rafael
Published: August 2018

Neuronal ensembles are building blocks of cortical activity yet it is unclear if they have any causal role in behavior. Here we tested if the precise activation of neuronal ensembles with two-photon holographic optogenetics in mouse primary visual cortex alters behavioral performance in a visual task. Disruption of behaviorally relevant cortical ensembles by activation of non-selective neurons decreased behavioral performance whereas optogenetic targeting of as few as two neurons with pattern completion capability from behaviorally relevant ensembles improved task performance by reliably recalling the whole ensemble. Moreover, in some cases, activation of two pattern completion neurons, in the absence of visual stimulus, triggered correct behavioral responses. Our results demonstrate a causal role of neuronal ensembles in a visually guided behavior and suggest that ensembles could represent perceptual states.
Elevated P2×7r and P2×4r transcripts levels in the Flinders Sensitive Line Rats, a genetic animal model of depression
Authors: Ribeiro Deidiane Elisa , Müller Heidi Kaastrup , Elfving Betina , Joca Samia Regiane Lourenço , Wegener Gregers
Published: August 2018

P2×7 and P2×4 receptors (P2×7R and P2×4R, respectively) are ligand-gated ion channels activated by adenosine triphosphate (ATP), which have been associated to dysfunctional processes in stress responses linked to depression, such as neurotransmitter release, cognition, sleep, energy, appetite, immune and endocrine dysfunction. Clinical studies indicate that polymorphisms in the P2×7r gene results in increased susceptibility for development of depression. Existing studies have investigated the role of P2×7R and P2×4R in animal models based on stress exposure. Therefore, the present work aimed to investigate the transcript and protein levels of these receptors in a genetic animal model of depression, the Flinders Sensitive Line (FSL) and its control group, the Flinders Resistant Line (FRL) rats. We found that FSL rats have increased transcript levels of P2×7R and P2×4R in frontal cortex (FC), ventral and dorsal hippocampus (vHip and dHip, respectively) compared to FRL rats. There were no alterations in the protein levels in the FC and dHip, but the P2×7R was lower in FSL than in FRL rats in the vHip. The results suggest that increased transcripts levels of P2×7r and P2×4r in the FSL rats may contribute to the stress-susceptibility observed in these animals.
Cartilaginous and osteochondral tissue formation by human mesenchymal stem cells on three-dimensionally woven scaffolds
Authors: Larson Benjamin L. , Yu Sarah N. , Park Hyoungshin , Estes Bradley T. , Moutos Franklin T. , Bloomquist Cameron J. , Wu Patrick B. , Welter Jean F. , Langer Robert , Guilak Farshid , Freed Lisa E.
Published: August 2018

The development of mechanically functional cartilage and bone tissue constructs of clinically relevant size, as well as their integration with native tissues, remain important challenges for regenerative medicine. The objective of this study was to assess adult human mesenchymal stem cells (MSC) in large, three dimensionally woven poly(ε-caprolactone) (PCL) scaffolds in proximity to viable bone, both in a nude rat subcutaneous pouch model and under simulated conditions in vitro. In Study I, various scaffold permutations: PCL alone, PCL-bone, “point-of- care” seeded MSC-PCL-bone, and chondrogenically pre-cultured Ch-MSC-PCL-bone constructs were implanted in a dorsal, ectopic pouch in a nude rat. After eight weeks, only cells in the Ch- MSC-PCL constructs exhibited both chondrogenic and osteogenic gene expression profiles. Notably, while both tissue profiles were present, constructs that had been chondrogenically pre- cultured prior to implantation showed a loss of glycosaminoglycan (GAG) as well as the presence of mineralization along with the formation of trabecula-like structures. In Study II of the study, the GAG loss and mineralization observed in Study I in vivo were recapitulated in vitro by the presence of either nearby bone or osteogenic culture medium additives but were prevented by a continued presence of chondrogenic medium additives. These data suggest conditions under which adult human stem cells in combination with polymer scaffolds synthesize functional and phenotypically distinct tissues based on the environmental conditions, and highlight the potential influence that paracrine factors from adjacent bone may have on MSC fate, once implanted in vivo for chondral or osteochondral repair.
Higher-order thalamic circuits channel parallel streams of visual information in mice
Authors: Bennett Corbett , Gale Samuel D. , Garrett Marina E. , Newton Melissa L. , Callaway Edward M. , Murphy Gabe J. , Olsen Shawn R.
Published: August 2018

Higher-order thalamic nuclei, such as the visual pulvinar, play essential roles in cortical function by connecting functionally-related cortical and subcortical brain regions. Yet a coherent framework describing pulvinar function remains elusive due to its anatomical complexity and involvement in diverse cognitive processes. Here we combined large-scale anatomical circuit mapping with high-density electrophysiological recordings to dissect a homolog of pulvinar in mice, the lateral posterior nucleus (LP). We define three broad LP subregions based on correspondence between input/output connectivity and functional properties. These subregions form corticothalamic loops biased towards ventral or dorsal stream cortical areas and contain separate representations of visual space. To reveal which input sources drive LP activity, we silenced visual cortex or superior colliculus and found they drive visual tuning properties in separate LP subregions. Thus, by specifying the driving input sources, functional properties, and downstream targets of LP circuits, our data provide a roadmap for understanding the mechanisms of higher-order thalamic function in vision.
Distinct structure of cortical population activity on fast and infraslow timescales
Authors: Okun Michael , Steinmetz Nicholas A. , Lak Armin , Dervinis Martynas , Harris Kenneth D.
Published: August 2018

Cortical activity is organised across multiple spatial and temporal scales. Most research on the dynamics of neuronal spiking is concerned with timescales of 1 ms − 1 s, and little is known about spiking dynamics on timescales of tens of seconds and minutes. Here, we used frequency domain analyses to study the structure of individual neurons’ spiking activity and its coupling to local population rate and to arousal level across frequencies ranging from 0.01 to 100 Hz. In mouse medial prefrontal cortex (mPFC), the spiking dynamics of individual neurons could be quantitatively captured by a combination of interspike interval and firing rate power spectrum distributions. The relative strength of coherence with local population often differed across timescales: a neuron strongly coupled to population rate on fast timescales could be weakly coupled on slow timescales, and vice versa. On slow but not fast timescales, a substantial proportion of neurons showed firing anti-correlated with the population. Infraslow firing rate changes were largely determined by arousal rather than by local factors, which could explain the timescale dependence of population coupling strength of individual neurons. These observations demonstrate how individual neurons simultaneously partake in fast local dynamics, and slow brain-wide dynamics, extending our understanding of infraslow cortical activity beyond the mesoscale resolution of fMRI studies.
A diencephalic pathway for movement initiation and rescue of Parkinsonian symptoms
Authors: Watson Glenn D.R. , Hughes Ryan N. , Petter Elijah A. , Yin Henry H.
Published: August 2018

The parafascicular nucleus (Pf) of the thalamus projects to the subthalamic nucleus (STN), a major target for deep brain stimulation (DBS) in Parkinson’s disease (PD), but the function of this projection remains unknown. Here, we used optogenetics, 3D motion capture, in vivo electrophysiology and 1-photon calcium imaging, unsupervised behavioral classification, and viral-based neuroanatomical tracing to examine the contribution of Pf efferents to movement generation in mice. We discovered that Pf neurons are highly correlated with movement velocity and excitation of Pf neurons generates turning and orienting movements. Movement initiation was not due to Pf projections to the striatum, but rather its projections to the STN. Optogenetic excitation of the Pf-STN pathway restores movement in a common mouse model of PD with complete akinesia. Collectively, our results reveal a thalamo-subthalamic pathway regulating movement initiation, and demonstrate a circuit mechanism that could potentially explain the clinical efficacy of DBS for relief of PD motor symptoms.
Early arrival at breeding grounds: Causes, costs and a trade‐off with overwintering latitude
Authors: Rotics Shay , Kaatz Michael , Turjeman Sondra , Zurell Damaris , Wikelski Martin , Sapir Nir , Eggers Ute , Fiedler Wolfgang , Jeltsch Florian , Nathan Ran
Published: August 2018

Early arrival at breeding grounds is of prime importance for migrating birds as it is known to enhance breeding success. Adults, males and higher quality individuals typically arrive earlier, and across years, early arrival has been linked to warmer spring temperatures. However, the mechanisms and potential costs of early arrival are not well understood.

To deepen the understanding of arrival date differences between individuals and years, we studied them in light of the preceding spring migration behaviour and atmospheric conditionsen route.

GPSand body acceleration (ACC) data were obtained for 35 adult white storks (Ciconia ciconia) over five years (2012–2016).ACCrecords were translated to energy expenditure estimates (overall dynamic body acceleration;ODBA) and to behavioural modes, andGPSfixes were coupled with environmental parameters.

At the interindividual level (within years), early arrival was attributed primarily to departing earlier for migration and from more northern wintering sites (closer to breeding grounds), rather than to migration speed. In fact, early‐departing birds flew slower, experienced weaker thermal uplifts and expended more energy during flight, but still arrived earlier, emphasizing the cost and the significance of early departure. Individuals that wintered further south arrived later at the breeding grounds but did not produce fewer fledglings, presumably due to positive carry‐over effects of advantageous wintering conditions (increased precipitation, vegetation productivity and daylight time). Therefore, early arrival increased breeding success only after controlling for wintering latitude. Males arrived slightly ahead of females. Between years, late arrival was linked to colder temperaturesen routethrough two different mechanisms: stronger headwinds causing slower migration and lower thermal uplifts resulting in longer stopovers.

This study showed that distinct migratory properties underlie arrival time variation within and between years. It highlighted (a) an overlooked cost of early arrival induced by unfavourable atmospheric conditions during migration, (b) an important fitness trade‐off in storks between arrival date and wintering habitat quality and (c) mechanistic explanations for the negative temperature–arrival date correlation in soaring birds. Such understanding of arrival time can facilitate forecasting migrating species responses to climate changes.
Review article: Common emergency department presenting complaints of prisoners: A systematic review
Authors: Harel Nadav , Moskovitch Jeremy T , Weiland Tracey J , Augello Michael R
Published: August 2018

Prisoners are a particularly vulnerable minority group whose healthcare needs and management differ substantially from the general population. The overall burden of disease of prisoners is well documented; however, little is known regarding the aetiology and frequency of prisoners’ acute medical complaints requiring an ED visit. Objectives of the review were to identify, review and appraise existing literature regarding prisoners’ presentations to EDs. We performed systematic electronic searches in MEDLINE, EMBASE, PsycINFO, PubMed, Cochrane, and Web of Science using MeSH terms and keywords. Two reviewers abstracted data and conducted quality appraisal using the Quality Assessment Tool for Observational Cohort and Cross‐Sectional Studies. Nine articles met the predefined inclusion criteria. Apart from two European studies in the past 5 years, there is a scarcity of literature primarily addressing the common presenting complaints to EDs by prisoners. Existing studies demonstrated that prisoners have a disproportionately high burden of traumatic, infectious and psychiatric disease requiring emergency treatment. With the increasing number of emergency presentations made by prisoners each year, it is vital that further research is undertaken to identify trends of these acute medical complaints in order to ensure optimal therapeutic outcomes for prisoners.
Practical Ways to Achieve Targets in Diabetes Care
Authors: Rentzepis Peter J. , Kurian Martin J. , Carracher Ann M. , Close Kelly L.
Published: August 2018

Peter J. Rentzepis, Martin J. Kurian, Ann M. Carracher, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Rentzepis, Kurian, Carracher, and Close review the latest developments relevant to researchers and clinicians.
How to predict fine resolution occupancy from coarse occupancy data
Authors: Groom Quentin J. , Marsh Charles J. , Gavish Yoni , Kunin William E.
Published: August 2018

The area of occupancy (AOO) is a widely used index in conservation assessments, notably in criteria B2 of the International Union for Conservation of Nature (IUCN) red‐list. However, IUCN guidelines require assessing AOO at finer resolution than is generally available. For this reason, extrapolation techniques have been proposed to predict finer AOO from coarser resolution data.

Here, we apply 10 published downscaling models to the distributions of a large number of plant and bird species' in contrasting landscapes. We further compare the output of two ensemble models, one relying on all 10 downscaling models and one a subset of five models that can be fit rapidly and robustly, with minimal oversight required. We further compare the accuracy of downscaled predictions with respect to species prevalence.

Across all landscapes and taxa, the models predicted AOO consistently. Some, such as the power law and Hui models, were nonlinear with respect to species prevalence. Some models consistently over or under predicted, such as the Nachman and Poisson models. Furthermore, some models proved to give more variable predictions than other models, e.g. Nachman and power law. For these reasons, none of these models are suitable for downscaling if used individually. The Thomas model was also rejected, because it is too computationally intensive, even though its predictions are relatively unbiased. The most effective model, when used by itself, was the improved binomial model. However, the two ensemble models were able to provide accurate predictions of AOO with low variability compared to using any one single model. There was no significant loss in performance using the simpler ensemble model, and therefore this solution is the least computationally intensive and requires least user oversight.

Our results show that downscaling models could be potential tools to reliably estimate AOO for conservation assessments. Under circumstances where there is no a priori reason to prefer one model over another then an ensemble of these models may be the best solution for batch analysis of IUCN status under criteria B2. Moreover, we foresee the use of downscaling for the production of other biodiversity indicators, such as for invasive species monitoring.
Clinical Usefulness of the Iowa Gambling Task in Severe Alcohol Use Disorders: Link with Relapse and Cognitive‐Physiological Deficits
Authors: Maurage Pierre , Lannoy Séverine , Dormal Valérie , Blanco Marine , Trabut Jean‐Baptiste
Published: August 2018

Background

Decision‐making impairments have been repeatedly evaluated in severe alcohol use disorders (SAUD) using the Iowa Gambling Task (IGT). The IGT, capitalizing on strong theoretical background and ecological significance, allowed identifying large‐scale deficits in this population and is now a standard decision‐making assessment in therapeutic settings. However, the clinical usefulness of the IGT, particularly regarding its ability to predict relapse and its link with key cognitive‐physiological deficits, remains to be clarified.

Methods

Thirty‐eight recently detoxified patients with SAUD and 38 matched healthy controls performed the IGT, a neuropsychological task using monetary rewards to assess decision making under uncertainty and under risk. Disease characteristics (e.g., duration and intensity), cognitive abilities, psychopathological comorbidities, and physiological damage were also measured, as well as relapse rates 6 months later.

Results

Compared to controls, patients with SAUD presented a dissociation between preserved decision making under uncertainty and impaired decision making under risk. In the SAUD group, while relapsers (55% of the sample) presented lower global cognitive functioning and stronger liver damage than nonrelapsers at detoxification time, no difference was found between these subgroups for the IGT. IGT results were not related to alcohol‐consumption characteristics or cognitive‐physiological deficits.

Conclusions

SAUD is not related to a global IGT deficit, as suggested earlier, but rather to a specific impairment for decision making under risk. This deficit is not associated with other disease‐related variables and has no relapse prediction power. These results question the clinical usefulness of the IGT as a tool identifying key treatment levers and guiding (neuro)psychological rehabilitation.
Ethanol (EtOH)‐Related Behaviors in α‐Synuclein Mutant Mice and Association of SNCA SNPs with Anxiety in EtOH‐Dependent Patients
Authors: Persyn Wolfgang , Houchi Hakim , Papillon Charles‐Antoine , Martinetti Margaret , Antol Johann , Guillaumont Cyrille , Dervaux Alain , Naassila Mickael
Published: August 2018

Background

Data have shown a role of α‐synuclein in anxiety and also in addiction, particularly in alcohol use disorders (AUD). Since the comorbidity between AUD and anxiety is very high and because anxiety is an important factor in ethanol (EtOH) relapse, the aim of the present study was to investigate the role of α‐synuclein in moderating EtOH intake, the anxiolytic effects of EtOH, and EtOH withdrawal–induced anxiety and convulsions in mice. The study aimed to determine whether SNCA variants moderated anxiety in EtOH‐dependent patients.

Methods

We analyzed the moderator effect of 3 SNCA Tag‐single nucleotide polymorphisms (Tag‐SNPs) rs356200, rs356219, and rs2119787 on the anxiety symptoms in 128 EtOH‐dependent patients. We used the C57BL/6JOlaHsd Snca mutant mice to assess EtOH intake; sensitivity to the anxiolytic effects of EtOH in a test battery comprising the open field, the light–dark box, and the elevated plus maze; and both anxiety and convulsions induced by EtOH withdrawal.

Results

Our results demonstrated a reduction in both EtOH intake and preference and also a lack of sensitivity to the anxiolytic effects of EtOH in α‐synuclein mutant mice. Results on anxiety‐like behavior were mixed, but mutant mice displayed increased anxiety when exposed to a low anxiogenic environment. Mutant mice also displayed an increase in handling‐induced convulsion scores during withdrawal after EtOH inhalation, but did not differ in terms of EtOH withdrawal–induced anxiety. In humans, we found a significant association of the rs356219 SNP with a high level of anxiety (Beck Anxiety Inventory score >15) and the rs356200 SNP with a positive familial history of AUD.

Conclusions

Our translational study highlights a significant role of α‐synuclein in components of AUD.
Antennal asymmetry is not associated with social behaviour in Australian Hymenoptera
Authors: Freelance Christopher B , Majoe Megha , Tierney Simon M , Elgar Mark A
Published: August 2018

Lateralisation of biological form and function are well known for vertebrates and are being increasingly documented among invertebrates in recent years. Behavioural lateralisation in insects, together with asymmetrical distributions of antennal sensilla, has been linked to the communication challenges faced by social, but not solitary, insects. Recent evidence on patterns of asymmetry in insects outside of the Hymenoptera suggests that this explanation for antennal sensilla asymmetry may not be phylogenetically constrained. We explore this possibility by examining the distribution of antennal sensilla in three species of ants (Formicidae), the meat ant Iridomyrmex purpureus (Dolichoderinae), the green tree ant Oecophylla smaragdina (Formicinae) and the shield ant Meranoplus sp. (Myrmicinae) in which colony organisation is eusocial, and two species of nomiine bees, Mellitidia tomentifera and Reepenia bituberculata (Halictidae: Nomiinae), where colony organisation is not eusocial. Our results demonstrate that while there are differences in the left–right asymmetry of antennal sensilla basiconica in workers of the formicine ant I. purpureus, there is no consistent sensilla asymmetry across the five species. We find a negative correlation between antennal sensilla density and body size in R. bituberculata, which was not apparent in the other species. Our results contradict the suggestion that asymmetrical distribution of antennal sensilla is associated with the evolution of eusocial behaviour.
A randomised trial of serratus anterior plane block for analgesia after thoracoscopic surgery
Authors: Park M. H. , Kim J. A. , Ahn H. J. , Yang M. K. , Son H. J. , Seong B. G.
Published: August 2018

We evaluated the effect of pre‐operative serratus anterior plane block on postoperative pain and opioid consumption after thoracoscopic surgery. We randomly allocated 89 participants to block with 30 ml ropivacaine 0.375% (n = 44), or no block without placebo or sham procedure (n = 45). We analysed results from 42 participants in each group. Serratus anterior plane block reduced mean (SD) remifentanil dose during surgery, 0.12 (0.06) mg.h−1 vs. 0.16 (0.06) mg.h−1, p = 0.016, and reduced mean (SD) fentanyl consumption in the first 24 postoperative hours, 3.8 (1.9) μg.kg−1 vs. 5.7 (1.6) μg.kg−1, p = 0.000004. Block also reduced the worst median (IQR [range]) pain scores reported in the first 24 postoperative hours: 6 (5–7 [3–10]) vs. 7 (6–7 [3–10]), p = 0.027. Block decreased dissatisfaction with pain management, categorised as ‘highly unsatisfactory’, ‘unsatisfactory’, ‘neutral’, ‘satisfactory’ or ‘highly satisfactory’: 1/2/21/18/0 vs. 1/14/15/11/1, p = 0.0038. There were no differences in the rates of nausea, vomiting, dizziness or length of hospital stay. Serratus anterior plane block may be used to reduce pain and opioid use after thoracoscopic lung surgery.
General and sex profile of women with partner affected by premature ejaculation: results of a large observational, non‐interventional, cross‐sectional, epidemiological study (IPER‐F)
Authors: Verze P. , Arcaniolo D. , Imbimbo C. , Cai T. , Venturino L. , Spirito L. , Califano G. , La Rocca R. , Mirone V.
Published: August 2018

Background

Couple distress is a crucial point in premature ejaculation (PE). PE has been associated with significant bother, interpersonal problems, and dissatisfaction with sexual intercourse for both men and their partners.

Objectives

The primary objective of this study was to assess the effect of PE on female sexuality in female partners of men affected from PE. Secondary objectives were to assess the impact of PE on female sexual quality of life, to assess the presence of sexual problems of the male partner, and to evaluate the prevalence and characteristics of comorbidities.

Materials and methods

Adult women aged 18 to 80 years old, sexually active, were randomly sampled from the patient lists of General Practitioners in Italy and were included in this observational, non‐interventional, cross‐sectional epidemiological study. Subjects were asked to fill: a general questionnaire regarding anthropometric data, lifestyle, marital status, education, occupation, economic conditions, general health status, comorbidities, and sexual habits; the Sexual Quality of Life Questionnaire‐Female (SQoL‐F); the Female Sexual Distress Scale (FSDS‐R‐PE); the Self‐rating Depression Scale (SDS); and Self‐rating Anxiety Scale (SAS). In addition, females reported about their partner's ejaculation time and the presence of sexual dysfunctions.

Results

A total of 3,104 women were included. Mean age was 45.1 years. Woman with PE partners presented a higher percentage of sexual dysfunction and reported more anxiety compared with female partners of men not affected from PE (42.69% vs. 20.56% and 30.95% vs. 15,34%, respectively). In addition, they referred more sexual dysfunction in their partners. Hypertension, hypercholesterolemia, arthritis, heart diseases, thyroid disease, a history of menopause, or hysterectomy resulted in significantly more prevalence in women with PE partners.

Discussion and conclusions

Female partners of PE patients present an increased prevalence of sexual distress, a reduced quality of sexual life, and an increased anxiety score when compared to women whose partners are not affected from PE.
Vamorolone treatment improves skeletal muscle outcome in a critical illness myopathy rat model
Authors: Akkad Hazem , Cacciani Nicola , Llano‐Diez Monica , Corpeno Kalamgi Rebeca , Tchkonia Tamara , Kirkland James L. , Larsson Lars
Published: August 2018

Aim

Critical illness myopathy (CIM) is a consequence of modern critical care, leading to skeletal muscle atrophy/paralysis with negative consequences for mortality/morbidity and health care costs. Glucocorticoids (GCs) have been proposed to trigger CIM. Here, we compare outcomes of two GCs, the commonly used prednisolone and the newly developed dissociative vamorolone in response to the intensive care unit (ICU) condition for 5 days, ie, sedation, immobilization, and mechanical ventilation.

Methods

Rats were divided into a 0‐day sham‐operated control group, and three groups exposed to 5 days ICU condition during treatment with prednisolone (PRED) or vamorolone (VAM) or none of these GCs (ICU‐group). Survival, body and muscle weights, cytokine concentrations, regulation of muscle contraction in single fast‐ and slow‐twitch muscle fibres, myofibrillar protein expression and protein degradation pathways were studied.

Results

Critical illness myopathy geno‐ and pheno‐types were confirmed in the ICU group. However, VAM and PRED groups showed reduced atrophy/weakness than the ICU group, and muscle specific differences with more severe negative effects on fast‐twitch muscle fibres in the PRED than the other groups.

Conclusion

These results show that vamorolone provides a GC intervention superior to typical GCs in improving CIM outcomes. Further, the findings do not support the notion that moderate‐dose GC treatment represents a factor triggering CIM.
Are radio‐contrast agents commonly used in discography toxic to the intact intervertebral disc tissue cells?
Authors: Karaarslan Numan , Yilmaz Ibrahim , Ozbek Hanefi , Yasar Sirin Duygu , Kaplan Necati , Caliskan Tezcan , Ozdemir Cigdem , Akyuva Yener , Ates Ozkan
Published: August 2018

In the literature, there have been no studies showing clear results on how radio‐contrast pharmaceuticals would affect intact disc tissue cells. In this context, it was aimed to evaluate the effects of iopromide and gadoxetic acid, frequently used in the discography, on intact lumbar disc tissue in pharmaco‐molecular and histopathological level. Primary cell cultures were prepared from the healthy disc tissue of the patients operated in the neurosurgery clinic. Except for the control group, the cultures were incubated with the indicated radio‐contrast agents. Cell viability, toxicity and proliferation indices were tested at specific time intervals. The cell viability was quantitatively analysed. It was also visually rechecked under a fluorescence microscope with acridine orange/propidium iodide staining. Simultaneously, cell surface morphology was analysed with an inverted light microscope, while haematoxylin and eosin (H&E) staining methodology was used in the histopathological evaluations. The obtained data were evaluated statistically. Unlike the literature, iopromide or gadoxetic acid did not have any adverse effects on the cell viability, proliferation and toxicity (P < 0.05). Although this study reveals that radio‐contrast pharmaceuticals used in the discography, often used in neurosurgical practice, can be safely used, it should be remembered that this study was performed in an in vitro environment.
Commentary: Detecting unmet mental health needs in preschool children – A commentary on Barger et al. (2018)
Authors: Foreman David M.
Published: August 2018

Read the full article at doi: 10.1111/camh.12240

Read the Response to this Commentary at doi: 10.1111/camh.12276
Editorial perspective: Treatment of complex maltreatment – beyond the NICE guideline? Manuals, muddles or modules
Authors: Bentovim Arnon , Vizard Eileen , Gray Jenny
Published: August 2018

Providing adequate treatment services for maltreated children is a considerable challenge. The recently updated NICE guideline on Child abuse and neglect (NICE guideline [NG276] 2017, London) includes recommendations on intervention for a variety of parenting contexts, and different forms of maltreatment at various stages of identification: ‘Early Help for families showing possible signs of abuse and neglect’, and ‘Therapeutic interventions for children, young people and families, after child abuse and neglect’. The fifteen evidence‐based manualised approaches to be considered for use by practitioners are valuable and backed up by appropriate research on effectiveness. Approaches are selected which could be applied to more than one form of maltreatment. However, the manualised approaches reviewed by NICE have differing theoretical frameworks and attempting to put together an intervention for more complex forms of maltreatment, based solely on these approaches, may result in confusion and muddle. In practice, polyvictimisation or multipart maltreatment is now seen as the rule, rather than the exception. In these cases, whole sibships may be affected, with children of different ages and stages of development presenting with differing needs. As a result, there is a cumulative, negative impact on their health and development. As Macdonald et al. (Health Technology Assessment, 2016, 20, 1) state, ‘Most children experience more than one form of maltreatment, and there is growing recognition of the need to better take into account children's profiles of maltreatment in order to improve policy and practice’ (p. 38). Marchette and Weisz (Journal of Child Psychology and Psychiatry, 2017, 58, 970) draw attention to the paradox that there are many focal treatment manuals in the child mental health field, which have contributed to practice, but which are not used widely in everyday practice, due to a focus on single disorders rather than the reality of comorbid, co‐occurring problems. Few practitioners or service providers have the time or resources to learn a different approach for each disorder or problem type. A solution is the development of modular approaches. Effective practice elements can be ‘distilled’ from the intervention approaches recommended by NICE and from other evidence‐based interventions identified (Bentovim and Elliott, Journal of Clinical Child and Adolescent Psychology, 2014 43, 270). Practice elements can be integrated into a flexible modular approach to intervention which can be tailored to fit the complex profiles of those maltreated children, young people and their families whom practitioners work within their everyday practice.
Editorial Perspective: Antidepressants and the depressed adolescent
Authors: Goodyer Ian M.
Published: August 2018

A paper considering the role of antidepressants for adults with major depression was recently published in the Lancet, a world leading medical journal (Cipriani et al. 2018). The review was the largest ever on this topic based on 28,552 citations including 522 trials comprising 116,477 participants. The authors note that, in adults with major depression, all antidepressants were more efficacious than placebo. In head‐to‐head studies, the authors also note that agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious. The authors report that the standardised mean difference was 0.3 a moderate effect size for any antidepressant over placebo, this is confirmatory of past reviews noting rather similar magnitudes of effect. In clinical terms the results suggest a choice for practitioners in regard to their individual patients. For many adult depressed patients however, there is also the implication that antidepressants may not work. The old adage ‘what works for whom’ remains unanswered. What does seem reasonable to conclude is that we have learnt that these medications are clinically effective and the questions for research now must be who is likely to benefit and who is not, how do these medicines work, and what is the best long‐term management of responders as the majority of studies have focused on acute response only.
Commentary: On action guidance and good practice in early intervention for psychosis: a response to Bortolotti & Jefferson (2018)
Authors: Corsico Paolo , Singh Ilina
Published: August 2018

In this response to Bortolotti and Jefferson (2018), we discuss the action‐guidance problem of moral attributes and the risk of superiority illusion in early intervention for psychosis. First, we suggest that guidance documents are not devoid of behavioural recommendations and goals for service provision, though these are not linked to the ethical dimensions of good practice embedded in the documents. Second, we acknowledge the risk of superiority illusion; we suggest that this risk may be reduced if the ethical and clinical goals of early intervention are presented as interrelated and measurable.
Comparative analysis of immune cell subsets in peripheral blood from patients with periodontal disease and healthy controls
Authors: Cheng W-C , Saleh F , Abuaisha Karim B , Hughes F J , Taams L S
Published: August 2018

Periodontitis is a chronic inflammatory disease caused by the colonization of teeth by the bacterial plaque biofilm and the resultant host immune responses in adjacent periodontal tissues. Disease severity can vary dramatically between patients with periodontitis, with some subjects displaying inflammation without bony destruction (gingivitis), while others experience chronic progressive or rapidly aggressive gingival connective tissue damage and bone loss. To determine whether peripheral immune dysregulation is associated with periodontitis, we performed extensive analysis of immune cell subsets in peripheral blood from patients with chronic or aggressive periodontitis versus periodontally healthy control subjects. Peripheral blood mononuclear cells (PBMC) from patients with chronic periodontitis or aggressive periodontitis and from periodontally healthy controls were analysed by 8–10-colour flow cytometry for the frequencies of various lymphocyte subsets, including interleukin (IL)-17-, interferon (IFN)-γ-, tumour necrosis factor (TNF)-α- and IL-10-producing cells, and the frequencies and phenotype of monocytes. Cytokine levels in serum from the different groups were determined by Luminex assay. We found no significant differences in the frequencies of major immune cell populations [CD4+ T cells, CD8+ T cells, γδ T cells, CD4+CD45RO+CD25+CD127low regulatory T cells (Tregs), CD19+ B cells, CD14+ monocytes] or of cytokine-producing T cells, or in the phenotype of CD14+ monocytes in peripheral blood from these patient cohorts. Additionally, no significant differences were observed in serum levels of prototypical inflammatory cytokines. These results suggest that the local gingival inflammatory response is not reflected by obvious changes in major blood immune cell subset frequencies.