bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRPM4 conductances in thalamic reticular nucleus neurons generate persistent firing during slow oscillations
Authors: O’Malley John J. , Seibt Frederik , Chin Jeannie , Beierlein Michael 
Published: February 2020

AbstractDuring sleep, neurons in the thalamic reticular nucleus (TRN) participate in distinct types of oscillatory activity. While the reciprocal synaptic circuits between TRN and sensory relay nuclei are known to underlie the generation of sleep spindles, the mechanisms regulating slow (<1 Hz) forms of thalamic oscillations are not well understood. Underin vitroconditions, TRN neurons can generate slow oscillations in a cell-intrinsic manner, with postsynaptic Group 1 metabotropic glutamate receptor (mGluR) activation leading to the generation of plateau potentials mediated by both T-type Ca2+currents and Ca2+-activated nonselective cation currents (ICAN). However, the identity of ICANand the possible contribution of thalamic circuits to slow rhythmic activity remain unclear. Using thalamic slices derived from adult mice of either sex, we recorded slow forms of rhythmic activity in TRN neurons, which were mediated by fast glutamatergic thalamoreticular inputs but did not require postsynaptic mGluR activation. For a significant fraction of TRN neurons, synaptic inputs or brief depolarizing current steps led to long-lasting plateau potentials and persistent firing (PF), and in turn, resulted in sustained synaptic inhibition in postsynaptic relay neurons of the ventrobasal thalamus (VB). Pharmacological approaches indicated that plateau potentials were triggered by Ca2+influx through T-type Ca2+channels and mediated by Ca2+and voltage-dependent transient receptor potential melastatin 4 (TRPM4) channels. Taken together, our results suggest that thalamic circuits can generate slow oscillatory activity, mediated by an interplay of TRN-VB synaptic circuits that generate rhythmicity and TRN cell-intrinsic mechanisms that control PF and oscillation frequency.Significance StatementSlow forms of thalamocortical rhythmic activity are thought to be essential for memory consolidation during sleep and the efficient removal of potentially toxic metabolites.In vivo, thalamic slow oscillations are regulated by strong bidirectional synaptic pathways linking neocortex and thalamus. Therefore,in vitrostudies in the isolated thalamus can offer important insights about the ability of individual neurons and local circuits to generate different forms of rhythmic activity. We found that circuits formed by GABAergic neurons in the thalamic reticular nucleus (TRN) and glutamatergic relay neurons in the ventrobasal thalamus generated slow oscillatory activity, which was accompanied by persistent firing in TRN neurons. Our results identify both cell-intrinsic and synaptic mechanisms that mediate slow forms of rhythmic activity in thalamic circuits.
Radixin modulates stereocilia function and contributes to cochlear amplification
Authors: Prasad Sonal , Vona Barbara , Diñeiro Marta , Costales María , González-Aguado Rocío , Fontalba Ana , Diego-Pérez Clara , Subasioglu Asli , Bademci Guney , Tekin Mustafa , Cabanillas Rubén , Cadiñanos Juan , Fridberger Anders 
Published: February 2020

AbstractThe stereocilia of the sensory cells in the inner ear contain high levels of the actin-binding protein radixin, encoded by theRDXgene. Radixin which is associated with mechanotransduction process such as PIP2is known to be important for hearing but its functional role remains obscure. To determine how radixin influences hearing sensitivity, we used a custom rapid imaging technique to directly visualize stereocilia motion while measuring the amplitude of the electrical potentials produced by sensory cells during acoustic stimulation. Experiments were performed in guinea pigs, where upon blocking radixin, a large decrease in sound-evoked electrical potentials occurred. Despite this decrease other important functional measures, such as electrically induced sensory cell motility and the sound-evoked deflections of stereocilia, showed a minor amplitude increase. This unique set of functional properties alterations demonstrate that radixin is necessary to ensure that the inner ear converts sound into electrical signals at acoustic rates. Radixin is therefore a necessary and important component of the cochlear amplifier, the energy-consuming process that boosts hearing sensitivity by up to 60 dB.
Use of Bioelectric Impedance Analysis (BIA) as a new method to detect prostate cancer
Authors: Bartoletti Riccardo , Greco Alberto , Di Vico Tommaso , Durante Jacopo , Ficarra Vincenzo , Scilingo Enzo Pasquale , Valenza Gaetano 
Published: February 2020

AbstractBackgroundTo determine the accuracy of a novel BIA test endorectal probe.MethodsOne hundred-forty consecutive patient candidates to prostate biopsy and 40 healthy volunteers were selected (NCT03428087). Total PSA and PSA density (PSAD) determinations, digital rectal examination (DRE), and the BIA test were analysed in patients and controls. A 16 cores trans rectal prostate biopsy was performed on all patients with clinical suspicion of PCa after a multiparametric MRI (mMRI) test. The study endpoints were to determine accuracy of BIA test in comparison to PSA, PSAD levels, and mMRI and obtain PCa prediction in candidates to prostate biopsy by BIA test. The Mann-Withney U test, the Wilkoxon rank test, and Holm-Bonferroni’s method were adopted for statistical analyses, and a computational approach was also applied to differentiate patients with PCa from those with benign disease (BPH).ResultsCombined DRE, TRUS, PSA, and PSAD alone failed to satisfactorily discern patients with PCa from those with BPH (62.86% of discrimination accuracy) and mMRI PIRADS ≥3 showed a sensitivity of 83% and a specificity of 59%. The accuracy in discerning PCa and BPH increased up to 75% by BIA test (sensitivity 63.33% and specificity 83.75%).ConclusionsThe BIA test is a simple, promising, cheap, and reliable test for PCa non-invasive diagnosis. The novel finger probe may improve PCa detection also in patients with low-risk PCa, thus reducing the need of useless biopsies.
Novel hemorrhage models of cerebral cavernous malformations
Authors: Detter Matthew R , Shenkar Robert , Benavides Christian R , Neilson Catherine A , Moore Thomas , Lightle Rhonda , Hobson Nicholas , Shen Le , Cao Ying , Girard Romuald , Zhang Dongdong , Griffin Erin , Gallione Carol J , Awad Issam A , Marchuk Douglas A 
Published: February 2020

AbstractCerebral cavernous malformations (CCMs) are ectatic capillary-venous malformations that develop in approximately 0.5% of the population. Patients with CCMs may develop headaches, focal neurologic deficits, seizures, and hemorrhages. While symptomatic CCMs, depending upon the anatomic location, can be surgically removed, there is currently no pharmaceutical therapy to treat CCMs. Several mouse models have been developed to better understand CCM pathogenesis and test therapeutics. The most common mouse models induce a large CCM burden that is anatomically restricted to the cerebellum and contributes to lethality in the early days of life. These inducible models thus have a relatively short period for drug administration. We developed an inducible CCM3 mouse model that develops CCMs after weaning and provides a longer period for potential therapeutic intervention. Using this new model, three recently proposed CCM therapies - fasudil, tempol, vitamin D3, and a combination of the three drugs failed to substantially reduce CCM formation when treatment was administered for five weeks, from postnatal day 21 (P21) to P56. We next restricted Ccm3 deletion to the brain vasculature and provided greater time (121 days) for CCMs to develop chronic hemorrhage, recapitulating the human lesions. We also developed the first model of acute CCM hemorrhage by injecting mice harboring CCMs with lipopolysaccharide. These efficient models will enable future drug studies to more precisely target clinically relevant features of CCM disease: CCM formation, chronic hemorrhage, and acute hemorrhage.
Metabolic flexibility allows generalist bacteria to become dominant in a frequently disturbed ecosystem
Authors: Chen Ya-Jou , Leung Pok Man , Bay Sean K. , Hugenholtz Philip , Kessler Adam J. , Shelley Guy , Waite David W. , Cook Perran L. M. , Greening Chris 
Published: February 2020

AbstractEcological theory suggests that habitat disturbance differentially influences distributions of generalist and specialist species. While well-established for macroorganisms, this theory has rarely been explored for microorganisms. Here we tested these principles in permeable (sandy) sediments, ecosystems with much spatiotemporal variation in resource availability and other conditions. Microbial community composition and function was profiled in intertidal and subtidal sediments using 16S amplicon sequencing and metagenomics, yielding 135 metagenome-assembled genomes. Microbial abundance and composition significantly differed with sediment depth and, to a lesser extent, sampling date. Several generalist taxa were highly abundant and prevalent in all samples, including within orders Woeseiales and Flavobacteriales; genome reconstructions indicate these facultatively anaerobic taxa are highly metabolically flexible and adapt to fluctuations in resource availability by using different electron donors and acceptors. In contrast, obligately anaerobic taxa such as sulfate reducers (Desulfobacterales, Desulfobulbales) and proposed candidate phylum MBNT15 were less abundant overall and only thrived in more stable deeper sediments. We substantiated these findings by measuring three metabolic processes in these sediments; whereas the generalist-associated processes of sulfide oxidation and hydrogenogenic fermentation occurred rapidly at all depths, the specialist-associated process of sulfate reduction was restricted to deeper sediments. In addition, a manipulative experiment confirmed generalists outcompete specialist taxa during simulated habitat disturbance. Altogether, these findings suggest that metabolically flexible taxa become dominant in these highly dynamic environments, whereas metabolic specialism restricts bacteria to narrower niches. Thus, an ecological theory describing distribution patterns for macroorganisms likely extends to microorganisms. Such findings have broad ecological and biogeochemical ramifications.
Reduced Suprathreshold Auditory Nerve Responses are Associated with Thinner Temporal Cortex and Slower Processing Speed in Presbycusis
Authors: Delano Paul H. , Belkhiria Chama , Vergara Rodrigo C. , Martínez Melissa , Leiva Alexis , Andrade Maricarmen , Marcenaro Bruno , Torrente Mariela , Cristóbal Maass Juan , Delgado Carolina 
Published: February 2020

AbstractEpidemiological evidence shows an association between hearing loss and dementia in elderly people. However, the mechanisms that connect hearing impairments and cognitive decline are still unknown. Here we propose that a suprathreshold auditory-nerve impairment is associated with cognitive decline and brain atrophy. Methods: audiological, neuropsychological, and brain structural 3-Tesla MRI data were obtained from elders with different levels of hearing loss recruited in the ANDES cohort. The amplitude of waves I (auditory nerve) and V (midbrain) from auditory brainstem responses were measured at 80 dB nHL. We also calculated the ratio between wave V and I as a proxy of a suprathreshold brainstem function. Results: we included a total of 101 subjects (age: 73.5 ± 5.2 years (mean ± SD), mean education: 9.5 ± 4.2 years, and mean audiogram thresholds (0.5-4 kHz): 25.5 ± 12.0 dB HL). We obtained reliable suprathreshold waves V in all subjects (n=101), while replicable waves I were obtained in 92 subjects (91.1%). Partial Spearman correlations (corrected by age, gender, education and hearing thresholds) showed that reduced suprathreshold wave I responses were associated with thinner bilateral medial and inferior temporal cortex and, with slower processing speed as evidenced by the Trail-Making Test-A and digit symbol tests. Non-significant correlations were obtained between wave I amplitudes and other cognitive domains. Conclusions: These results evidence that reduced suprathreshold auditory nerve responses in presbycusis are associated with slower processing speed and brain structural changes in the temporal cortex.
Temporal and genetic variation in female aggression after mating
Authors: Bath Eleanor , Biscocho Edmund Ryan , Easton-Calabria August , Wigby Stuart 
Published: February 2020

AbstractAggression between individuals of the same sex is almost ubiquitous across the animal kingdom. Winners of intrasexual contests often garner considerable fitness benefits, through greater access to mates, food, or social dominance. In females, aggression is often tightly linked to reproduction, with females displaying increases in aggressive behavior when mated, gestating or lactating, or when protecting dependent offspring. In the fruit fly,Drosophila melanogaster, females spend twice as long fighting over food after mating as when they are virgins. However, it is unknown when this increase in aggression begins or whether it is consistent across genotypes. Here we show that aggression in females increases between 2 to 4 hours after mating and remains elevated for at least a week after a single mating. In addition, this increase in aggression 24 hours after mating is consistent across three diverse genotypes, suggesting this may be a universal response to mating in the species. We also report here the first use of automated tracking and classification software to study female aggression inDrosophilaand assess its accuracy for this behavior. Dissecting the genetic diversity and temporal patterns of female aggression assists us in better understanding its generality and adaptive function, and will facilitate the identification of its underlying mechanisms.
Mitochondrial event localiser (MEL) to quantitatively describe fission, fusion and depolarisation in the three-dimensional space
Authors: Theart Rensu P , Kriel Jurgen , Loos Ben , Niesler Thomas R 
Published: February 2020

AbstractMitochondrial fission and fusion play an important role not only in maintaining mitochondrial homeostasis but also in preserving overall cellular viability. However, quantitative analysis based on the three-dimensional localisation of these highly dynamic mitochondrial events in the cellular context has not yet been accomplished. Moreover, it remains largely uncertain where in the mitochondrial network depolarisation is most likely to occur. We present the mitochondrial event localiser (MEL), a method that allows high-throughput, automated and deterministic localisation and quantification of mitochondrial fission, fusion and depolarisation events in large three-dimensional microscopy time-lapse sequences. In addition, MEL calculates the number of mitochondrial structures as well as their combined and average volume for each image frame in the time-lapse sequence. The mitochondrial event locations can subsequently be visualised by superposition onto the fluorescence micrograph z-stack. We apply MEL to both control samples as well as cells that have been treated with hydroxychloroquine sulphate (HCQ) and observe that fission and fusion events mostly occur around the terminal branches of the mitochondrial network, with few events detected in the strongly networked areas such as the perinuclear region. Depolarisation was most abundant in the HCQ treated samples, with the majority of the depolarisation events occurring in the cell periphery.
AFM characterization of the interaction of PriA helicase with stalled DNA replication forks
Authors: Wang Yaqing , Sun Zhiqiang , Bianco Piero R. , Lyubchenko Yuri L. 
Published: February 2020

ABSTRACTIn bacteria, the restart of stalled DNA replication forks requires the PriA DNA helicase. PriA recognizes and remodels abandoned DNA replication forks performing the DNA unwinding in 3’ to 5’-direction and facilitates loading of the DnaB helicase onto the DNA to restart replication. The single stranded DNA binding protein (SSB) is typically present at the abandoned forks, but there is gap in the knowledge on the interaction between SSB and PriA protein. Here, we used atomic force microscopy (AFM) to visualize the interaction of PriA with DNA substrates in the absence or presence of SSB. Results show that in the absence of SSB, PriA binds preferentially to a fork substrate with a gap in the leading strand. Preferential binding occurs only on forked DNA structures as 5’- and 3’-tailed duplexes were bound equally well. Furthermore, in the absence of SSB, PriA bound exclusively to the fork regions of substrates. In contrast, fork bound SSB loads PriA onto the duplex DNA arms of forks. When the fork has a gap in the leading strand, PriA localizes to both the parental and lagging strand arms. When the gap is present in the lagging strand, PriA is loaded preferentially onto the leading strand arm of the fork. Remodeling of PriA requires a functional C-terminal domain of SSB.
A Myosin-7B dependent endocytosis pathway mediates cellular entry of α-Synuclein fibrils and polycation-bearing cargos
Authors: Zhang Qi , Xu Yue , Lee Juhyung , Jarnik Michal , Wu Xufeng , Bonifacino Juan S. , Shen Jingshi , Ye Yihong 
Published: February 2020

Cell-to-cell transmission of misfolding-prone α-Synuclein (α-Syn) has emerged as a key pathological event in Parkinson’s disease. This process is initiated when α-Syn-bearing fibrils enter cells via clathrin-mediated endocytosis, but the underlying mechanisms are unclear. Using a CRISPR-mediated knockout screen, we identify SLC35B2 and Myosin-7B (MYO7B) as critical endocytosis regulators for α-Synpreformedfibrils (PFF). We show that SLC35B2, as a key regulator of heparan sulfate proteoglycan (HSPG) biosynthesis, is essential for recruiting α-Syn PFF to the cell surface because this process is mediated by interactions between negatively charged sugar moieties of HSPGs and clustered K-T-K motifs in α-Syn PFF. By contrast, MYO7B regulates α-Syn PFF entry by maintaining a plasma-membrane-associated actin network that controls membrane dynamics. Without MYO7B or actin filaments, many clathrin-coated pits fail to be severed from the membrane, causing accumulation of large clathrin-containing ‘scars’ on the cell surface. Intriguingly, the requirement for MYO7B in endocytosis is only restricted to α-Syn PFF and other cargos that enter cells via HSPGs. Thus, by identifying new regulatory factors for α-Syn PFF endocytosis, our study defines a mechanistically distinct clathrin-mediated endocytosis pathway that requires additional force generated by MYO7B and actin filaments.SignificanceThe spreading of misfolded protein aggregates such as α-Synuclein preformed fibrils (α-Syn PFF) from cell to cell is a pathologic hallmark associated with the progression of many neurodegenerative diseases, but it is unclear how mammalian cells take up these large protein aggregates to initiate this prion-like protein transmission process. Here we define the mechanism of α-Syn PFF endocytosis using a combination of genetic, biochemical, and live-cell imaging techniques. Our study reveals how α-Syn PFF binds to the cell surface heparan sulfate proteoglycans using two lysine-bearing motifs and then enters cells following a Myosin-7B- and actin-dependent endocytosis mechanism that is specifically tailored for polycation-bearing cargos.
Experimental and CFD study of slotted Krueger flaps aerodynamics in critical locations
Authors: Kulhánek Robert , Pátek Zdeněk , Vrchota Petr , Procházka Pavel , Uruba Vaclav 
Published: February 2020

Purpose
Some recent effort showed that usage of Krueger flaps helps to maintain laminar flow in cruise flight. Such flaps are positioned higher relative to the chord to shield the leading edge from the insect contamination during take-off. The flap passes several through critical intermediate position during the deployment to its design position. The purpose of this paper is to analyse the aerodynamics.

Design/methodology/approach
To better understand such flow phenomena, the combined approach of computational fluid dynamics and experimental methods were used. Flow simulation was performed with in-house finite volume Navier–Stokes solver in fully turbulent unsteady RANS regime. The experimental data were obtained by means of force and pressure measurements and some areas of the flow field were examined with 2 C particle image velocimetry.

Findings
The airfoil with flap in critical position has a very limited maximum lift coefficient. The maximum achievable lift coefficient during the deployment is significantly affected by the vertical position of the trailing edge of the flap. The most unfavourable position during the deployment is not the flap perpendicular to the chord, but the flap inclined closer to it is the retracted position.

Research limitations/implications
The flap movement was not simulated either in the simulation or in the experiment. Only intermediate static positions were examined.

Practical implications
A better understanding of aerodynamic phenomena connected with the deployment of a Krueger flap can contribute to the simpler and lighter of kinematics and also to decrease time-to-market.

Originality/value
Limited experimental and computational results of Krueger flap in critical positions during the deployment are published in the literature.
The interplay of stress and workspace attachment on user satisfaction and workspace support to labour productivity
Authors: Nappi Ingrid , de Campos Ribeiro Gisele , Cochard Nicolas 
Published: February 2020

Purpose
The purpose of this study is to evaluate how the relationship between employees’ workspace satisfaction and their respective perceptions of workspace support to labour productivity interacts with two emotional experiences as follows: workspace attachment and job stress.

Design/methodology/approach
Web-based surveys conducted before and after a company’s short-distance relocation. Study 1 concerned 66 employees and was conducted a few weeks before the relocation. Study 2 concerned 84 employees and was conducted six months after the relocation. Ordinary least squares regression, moderation and mediation analysis were performed.

Findings
After the relocation, the employees experienced greater job stress, less workspace satisfaction, and they felt less attached to their workspaces. However, the evaluations of workspace support to labour productivity did not change. Contrary to expectations, employees’ workspace satisfaction is not related to their evaluation of this workspace as supporting labour productivity. Instead, this relationship is moderated by job stress. The hypothesis that workspace attachment mediates the relationship between workspace satisfaction and respective evaluation of this workspace as supporting labour productivity was not verified.

Practical implications
Corporate real estate managers and any manager leading short-distance relocation projects should consider incorporating change management in the projects to maintain employees’ positive attitudes and emotional bonds with their workspace.

Originality/value
This research improves the knowledge of how employees perceive the workspace as supporting their work duties.