bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sucrose-mediated formation and adhesion strength of Streptococcus mutans biofilms on titanium
Authors: Waldman Laura J. , Butera Tony , Boyd James D. , Grady Martha E. 
Published: September 2022

ABSTRACTBiofilms consist of bacterial cells surrounded by a matrix of extracellular polymeric substance (EPS), which protects the colony from many countermeasures, including antibiotic treatments. Biofilm EPS composition is affected by environmental factors. In the oral cavity, the presence of sucrose affects the growth of Streptococcus mutans that produce acids, eroding enamel and forming dental caries. Biofilm formation on dental implants commonly leads to severe infections and failure of the implant. This work determines the effect of sucrose concentration on biofilm EPS formation and adhesion of Streptococcus mutans, a common oral colonizer. Bacterial biofilms are grown with varying concentrations of sucrose on titanium substrates simulating dental implant material. Strategies for measuring adhesion for films such as peel tests are inadequate for biofilms, which have low cohesive strength and will fall apart when tensile loading is applied directly. The laser spallation technique is used to apply stress wave loading to the biofilm, causing the biofilm to delaminate at a critical tensile stress threshold. Biofilm formation and EPS structures are visualized at high magnification with scanning electron microscopy (SEM). Biofilm substrate coverage and adhesion strength of biofilms initially increase with increasing sucrose concentration, but then decrease as sucrose concentration continues to increase. For biofilms grown with non-zero concentrations of sucrose, S. mutans adhesion to the substrate is higher than the adhesion of osteoblast-like cells to the same substrates. These results suggest sucrose-mediated adhesion and formation on titanium of S. mutans biofilms may outcompete osteoblasts during osseointegration, which could explain higher rates of peri-implant disease associated with high sugar diets.
Single-Cell Transcriptomic Profiling of the Zebrafish Inner Ear Reveals Molecularly Distinct Hair Cell and Supporting Cell Subtypes
Authors: Shi Tuo , Beaulieu Marielle O. , Saunders Lauren M. , Fabian Peter , Trapnell Cole , Segil Neil , Crump J. Gage , Raible David W. 
Published: September 2022

AbstractA major cause of human deafness and vestibular dysfunction is permanent loss of the mechanosensory hair cells of the inner ear. In non-mammalian vertebrates such as zebrafish, regeneration of missing hair cells can occur throughout life. While a comparative approach has the potential to reveal the basis of such differential regenerative ability, the degree to which the inner ears of fish and mammals share common hair cells and supporting cell types remains unresolved. Here we perform single-cell RNA sequencing of the zebrafish inner ear at embryonic through adult stages to catalog the diversity of hair cell and non-sensory supporting cells. We identify a putative progenitor population for hair cells and supporting cells, as well as distinct hair cells and supporting cell types in the maculae versus cristae. The hair cell and supporting cell types differ from those described for the lateral line system, a distributed mechanosensory organ in zebrafish in which most studies of hair cell regeneration have been conducted. In the maculae, we identify two subtypes of hair cells that share gene expression with mammalian striolar or extrastriolar hair cells. In situ hybridization reveals that these hair cell subtypes occupy distinct spatial domains within the two major macular organs, the utricle and saccule, consistent with the reported distinct electrophysiological properties of hair cells within these domains. These findings suggest that primitive specialization of spatially distinct striolar and extrastriolar hair cells likely arose in the last common ancestor of fish and mammals. The similarities of inner ear cell type composition between fish and mammals also support using zebrafish as a relevant model for understanding inner ear-specific hair cell function and regeneration.
RoboEM: automated 3D flight tracing for synaptic-resolution connectomics
Authors: Schmidt Martin , Motta Alessandro , Sievers Meike , Helmstaedter Moritz 
Published: September 2022

ABSTRACTMapping neuronal networks from 3-dimensional electron microscopy data still poses substantial reconstruction challenges, in particular for thin axons. Currently available automated image segmentation methods, while substantially progressed, still require human proof reading for many types of connectomic analyses. RoboEM, an AI-based self-steering 3D flight system trained to navigate along neurites using only EM data as input, substantially improves automated state-of-the-art segmentations and replaces human proof reading for more complex connectomic analysis problems, yielding computational annotation cost for cortical connectomes about 400-fold lower than the cost of manual error correction.
Death Induced by Survival gene Elimination (DISE) is correlated with neurotoxicity in Alzheimer’s disease and aging
Authors: Paudel Bidur , Jeong Si-Yeon , Martinez Carolina Pena , Rickman Alexis , Haluck-Kangas Ashley , Bartom Elizabeth T. , Fredriksen Kristina , Affaneh Amira , Kessler John A. , Mazzulli Joseph R. , Murmann Andrea E. , Rogalski Emily , Geula Changiz , Ferreira Adriana , Heckmann Bradlee L. , Green Douglas R. , Sadleir Katherine R. , Vassar Robert , Peter Marcus E. 
Published: September 2022

AbstractAlzheimer’s disease (AD) is characterized by progressive neurodegeneration, but the specific events that cause cell death remain poorly understood. Death Induced by Survival gene Elimination (DISE) is a cell death mechanism mediated by short (s) RNAs acting through the RNA induced silencing complex (RISC). DISE is thus a form of RNA interference, in which G-rich 6mer seed sequences in the sRNAs (position 2-7) target hundreds of C-rich 6mer seed matches in genes essential for cell survival, resulting in the activation of cell death pathways. Here, using Argonaute precipitation and RNAseq (Ago-RP-Seq), we analyze RISC-bound sRNAs to quantify 6mer seed toxicity in several model systems. In mouse AD models and aging brain, in induced pluripotent stem cell-derived neurons from AD patients, and in cells exposed to Aβ42 oligomers, RISC-bound sRNAs show a shift to more toxic 6mer seeds compared to controls. In contrast, in brains of “SuperAgers”, humans over age 80 who have superior memory performance, RISC-bound sRNAs are shifted to more nontoxic 6mer seeds. Cells depleted of nontoxic sRNAs are sensitized to Aβ42-induced cell death, and reintroducing nontoxic RNAs is protective. Altogether, the correlation between DISE and Aβ42 toxicity suggests that increasing the levels of nontoxic miRNAs in the brain or blocking the activity of toxic RISC-bound sRNAs could ameliorate neurodegeneration.
A membrane-associated light harvesting model is enabled by functionalized assemblies of gene-doubled TMV proteins
Authors: Dai Jing , Wilhelm Kiera B. , Bischoff Amanda J. , Pereira Jose H. , Dedeo Michel T. , García-Almedina Derek M. , Adams Paul D. , Groves Jay T. , Francis Matthew B. 
Published: September 2022

AbstractPhotosynthetic light harvesting requires efficient energy transfer within dynamic networks of light harvesting complexes embedded within phospholipid membranes. Artificial light harvesting models are valuable tools for understanding the structural features underpinning energy absorption and transfer within chromophore arrays. Most artificial light harvesting complexes are static or in the solution phase, rather than in a two-dimensional fluid environment as in natural photosynthesis. We have developed a method for attaching a protein-based light harvesting model to a supported lipid bilayer (SLB), which provides an extended fluid membrane surface stably associated with a solid substrate. The protein model consisted of the tobacco mosaic viral capsid proteins (TMV) that were gene-doubled to create a tandem dimer (dTMV). Assemblies of dTMV were shown to break the facial symmetry of the double disk to allow for differentiation between the disk faces. Single reactive lysine and cysteine residues were incorporated into opposing surfaces of each monomer of the dTMV assemblies. This allowed for the site-selective attachment of both chromophores for light absorption and a peptide for attachment to the SLB. A cysteine modification strategy using the enzyme tyrosinase was employed for the bioconjugation of a peptide containing a polyhistidine tag for association with SLBs. The dual-modified dTMV complexes showed significant association with SLBs and exhibited mobility on the bilayer. The techniques used herein offer a new method for protein-surface attachment and provide a platform for evaluating excited state energy transfer events in a dynamic, fully synthetic artificial light harvesting system.Significance StatementHere we have constructed a model photosynthetic membrane containing proteins, chromophores, lipids, and aqueous components, all of which can be modified in their composition. This model is based on an asymmetric disk assembly consisting of engineered tandem dimers of the tobacco mosaic viral capsid protein (dTMV). We have developed methods to achieve dye conjugation and attachment of a supported lipid bilayers (SLB) site selectively on distinct protein surfaces. These dye-labeled protein complexes exhibit mobility on the SLB, resulting in a dynamic model of light harvesting membranes using entirely synthetic components. Additionally, this unique asymmetric assembly of TMV and the facile methods for protein functionalization are expected to expand the tunability of model light harvesting systems.
Histone deacetylase 3 regulates microglial function through histone deacetylation
Authors: Meleady Laura , Towriss Morgan , Kim Jennifer , Bacarac Vince , Rowland Megan , Ciernia Annie Vogel 
Published: September 2022

AbstractBackgroundAs the primary innate immune cells of the brain microglia respond to damage and disease through pro-inflammatory release of cytokines and neuroinflammatory molecules. Histone acetylation is an activating transcriptional mark that regulates gene expression, which is altered in states of disease. Inhibition of histone deacetylase 3 (Hdac3) has been utilized in pre-clinical models of disease to dampen inflammation, but the molecular mechanisms underlying Hdac3’s regulation of inflammatory gene expression in microglia is not well understood.MethodsFunctional changes in immortalized microglia were characterized using a Hdac3 specific inhibitor RGFP966 in response to an immune challenge lipopolysaccharide (LPS). Flow cytometry and cleavage under tags & release using nucleases (CUT & RUN) were used to investigate global and promoter-specific histone acetylation changes, resulting in altered gene expression.ResultsHdac3 inhibition enhanced neuroprotective functions of microglia in response to LPS through reduced nitric oxide release and increased baseline phagocytosis. Inhibition of Hdac3 enhanced histone acetylation globally and at specific gene loci, resulting in the release of gene repression at baseline and enhanced responses to LPS.ConclusionThe findings suggest Hdac3 serves as a negative regulator of microglial gene expression, and that inhibition of Hdac3 facilitates the microglial response to inflammation and its subsequent resolution. Together, this work provides new mechanistic insights into therapeutic applications of Hdac3 inhibition which mediate reduced neuroinflammatory insults through microglial response.
Young Adults Use Whole-Body Feedback to Perceive Small Locomotor Disturbances
Authors: Liss Daniel J. , Carey Hannah D. , Allen Jessica L. 
Published: September 2022

AbstractTo prevent a fall when a disturbance to walking is encountered requires sensory information about the disturbance to be perceived, integrated, and then used to generate an appropriate corrective response. Prior research has shown that feedback of whole-body motion drives this corrective response. Here, we hypothesized that young adults also use whole-body motion to perceive locomotor disturbances. 15 subjects performed a locomotor discrimination task in which the supporting leg was slowed during stance every 8-12 steps to emulate subtle slips. The perception threshold of these disturbances was determined using a psychometrics approach and found to be 0.08 ± 0.03 m/s. Whole-body feedback was examined through center-of-mass (CoM) kinematics and whole-body angular momentum (WBAM). Perturbation-induced deviations of CoM and WBAM were calculated in response to the two perturbation levels nearest each subject’s perception threshold. Consistent with our hypothesis, we identified significantly higher perturbation induced deviations for perceived perturbations in sagittal-plane WBAM, anteroposterior CoM velocity, and mediolateral CoM position, velocity, and acceleration. Because whole body motion is not sensed directly but instead arises from the integration of various sensory feedback signals, we also explored local sensory feedback contributions to the perception of locomotor disturbances. Local sensory feedback was estimated through kinematic analogues of vision (head angle), vestibular (head angular velocity), proprioception (i.e., sagittal hip, knee, and ankle angles), and somatosensation (i.e., anterior-posterior & mediolateral center-of-pressure, COP). We identified significantly higher perturbation induced deviations for perceived perturbations in sagittal-plane ankle angle only. These results provide evidence for both whole-body feedback and ankle proprioception as important for the perception of subtle slip-like locomotor disturbances in young adults. Our interpretation is ankle proprioception is a dominant contributor to estimates of whole-body motion to perceive locomotor disturbances.
Proactive interhemispheric disinhibition supports response preparation during selective stopping
Authors: Wadsley Corey G. , Cirillo John , Nieuwenhuys Arne , Byblow Winston D. 
Published: September 2022

AbstractResponse inhibition is essential for terminating inappropriate actions. A substantial delay may occur in the response of the non-stopped effector when only part of a multi-effector action is terminated. This stopping-interference effect has been attributed to nonselective response inhibition processes and can be reduced with proactive cueing. This study aimed to elucidate the role of interhemispheric primary motor cortex (M1-M1) influences during selective stopping with proactive cueing. We hypothesized that stopping-interference would be reduced as stopping certainty increased, owing to proactive recruitment of interhemispheric facilitation or interhemispheric inhibition when cued to respond or stop, respectively. Twenty-three healthy human participants performed a bimanual anticipatory response inhibition paradigm with cues signaling the likelihood of a stop-signal occurring. Dual-coil transcranial magnetic stimulation was used to determine corticomotor excitability (CME), interhemispheric inhibition (IHI), and interhemispheric facilitation (IHF) in the left hand at rest and during response preparation. Response times slowed and stopping-interference decreased with cues signaling increased stopping certainty. Proactive response inhibition was marked by a reduced rate of rise and faster cancel time in electromyographical bursts during stopping. There was a nonselective release of IHI but not CME from rest to in-task response preparation, while IHF was not observed in either context. An effector-specific CME but not IHF or IHI reduction was observed when the left hand was cued to stop. These findings indicate that the stopping-interference effect can be reduced through proactive suppression. Interhemispheric M1-M1 channels modulate inhibitory tone that supports responding, but not selective stopping, in a proactive response inhibition context.Significance statementResponse inhibition is essential for terminating inappropriate actions and, in some cases, may be required for only part of a multi-effector action. The present study examined interhemispheric influences between the primary motor cortices during selective stopping with proactive cueing. Stopping selectivity was greater with increased stopping certainty and marked by proactive response inhibition of the hand cued to stop. Inhibitory interhemispheric influences were released during response preparation but were not affected by proactive cueing. These findings indicate that between-hand stopping can be selective with proactive cueing, but cue-related improvements are unlikely to reflect advance engagement of interhemispheric influences between primary motor cortices.
Specimen, Biological Structure, and Spatial Ontologies in Support of a Human Reference Atlas
Authors: Herr Bruce W. , Hardi Josef , Quardokus Ellen M. , Bueckle Andreas , Chen Lu , Wang Fusheng , Caron Anita R. , Osumi-Sutherland David , Musen Mark A. , Börner Katy 
Published: September 2022

AbstractThe Human Reference Atlas (HRA) is defined as a comprehensive, three-dimensional (3D) atlas of all the cells in the healthy human body. It is compiled by an international team of experts that develop standard terminologies linked to 3D reference objects describing anatomical structures. The third HRA release (v1.2) covers spatial reference data and ontology annotations for 26 organs. Experts access the HRA annotations via spreadsheets and view reference models in 3D editing tools. This paper introduces the Common Coordinate Framework Ontology (CCFO) v2.0.1 that interlinks specimen, biological structure, and spatial data together with the CCF API which makes the HRA programmatically accessible and interoperable with Linked Open Data (LOD). We detail how real-world user needs and experimental data guide CCFO design and implementation, present CCFO classes and properties together with examples of their usage, and report on technical validation performed. The CCFO graph database and API are used in the HuBMAP portal, Virtual Reality Organ Gallery, and other applications that support data queries across multiple, heterogeneous sources.
Synchronous multi-segmental activity between metachronal waves controls locomotion speed in Drosophila larvae
Authors: Liu Yingtao , Hasegawa Eri , Nose Akinao , Zwart Maarten F. , Kohsaka Hiroshi 
Published: September 2022

AbstractThe ability to adjust the speed of locomotion is essential for survival. In limbed animals, the frequency of locomotion is modulated primarily by changing the duration of the stance phase. The underlying neural mechanisms of this selective modulation remain an open question. Here, we report a neural circuit controlling a similarly selective adjustment of locomotion frequency in Drosophila larvae. Drosophila larvae crawl using peristaltic waves of muscle contractions. We find that larvae adjust the frequency of locomotion mostly by varying the time between consecutive contraction waves, reminiscent of limbed locomotion. A specific set of muscles, the lateral transverse (LT) muscles, co-contract in all segments during this phase, the duration of which sets the duration of the interwave phase. We identify two types of GABAergic interneurons in the LT neural network, premotor neuron A26f and its presynaptic partner A31c, which exhibit segmentally synchronized activity and control locomotor frequency by setting the amplitude and duration of LT muscle contractions. Altogether, our results reveal an inhibitory central circuit that sets the frequency of locomotion by controlling the duration of the period in between peristaltic waves. Further analysis of the descending inputs onto this circuit will help understand the higher control of this selective modulation.
Postoperative mortality analysis of national Japanese Diagnosis Procedure Combination database with a focus on regional comparisons and changes over time
Authors: Kunisawa Susumu 
Published: September 2022

AbstractPURPOSEThis study aimed to investigate postoperative mortality from all surgeries at the prefecture level using nationwide database, Japanese Diagnosis Procedure Combination (DPC) database, and to show those with visible changes over time or variations among areas.METHODSData were provided in accordance with the guidelines and application as indicated on the Ministry of Health, Labor and Welfare (MHLW), Japan. The number of cases and in-hospital mortality were calculated for each representative surgery for each hospitalization by fiscal year of discharge from 2011 to 2018 and by prefecture. Values of ≥10 in each aggregated data cell are presented.RESULTSThe aggregated result data contain 474,154 records, with about 2000 different surgical codes. Only in the 16,890 data, more than 10 mortalities were recorded, which can be used in the mortality analysis. In the analyses of artificial head insertion, cerebral aneurysm neck clipping, coronary artery and aortic bypass grafting, and tracheotomy, regional differences and a declining trend were observed in some categories.CONCLUSIONIn addition to considering categories that can be used in the analysis, careful consideration must be given to the inclusion of background context such as quality of care.
Economic evaluation of participatory women’s groups scaled up by the public health system to improve birth outcomes in Jharkhand, eastern India
Authors: Haghparast-Bidgoli Hassan , Ojha Amit , Gope Rajkumar , Rath Shibanand , Pradhan Hemanta , Rath Suchitra , Kumar Amit , Nath Vikash , Basu Parabita , Copas Andrew , Houweling Tanja A.J. , Minz Akay , Baskey Pradeep , Ahmed Manir , Chakravarthy Vasudha , Mahanta Riza , Palmer Tom , Skordis Jolene , Nair Nirmala , Tripathy Prasanta , Prost Audrey 
Published: September 2022

AbstractAn estimated 2.4 million newborn infants died in 2020, 80% of them in sub-Saharan Africa and South Asia. To achieve the Sustainable Development Target for neonatal mortality reduction, countries with high mortality need to implement evidence-based, cost-effective interventions at scale. Our study aimed to estimate the cost, cost-effectiveness, and benefit-cost ratio of a participatory women’s groups intervention scaled up by the public health system in Jharkhand, eastern India. The intervention was evaluated through a pragmatic cluster non-randomised controlled trial in six districts. We estimated the cost of the intervention from a provider perspective, with a 42-month time horizon for 20 districts. We estimated costs using a combination of top-down and bottom-up approaches. All costs were adjusted for inflation, discounted at 3% per year, and converted to 2020 International Dollars (INT$). Incremental cost-effectiveness ratios (ICERs) were estimated using extrapolated effect sizes for the impact of the intervention in 20 districts, in terms of cost per neonatal deaths averted and cost per life year saved. We assessed the impact of uncertainty on results through one-way and probabilistic sensitivity analyses. We also estimated benefit-cost ratio using a benefit transfer approach. Total intervention costs for 20 districts were INT$ 15,017,396. The intervention covered an estimated 1.6 million livebirths across 20 districts, translating to INT$ 9.4 per livebirth covered. ICERs were estimated at INT$ 1,272 per neonatal death averted or INT$ 41 per life year saved. Net benefit estimates ranged from INT$ 1,046 million to INT$ 3,254 million, and benefit-cost ratios from 71 to 218. Our study suggests that participatory women’s groups scaled up by the public health system are highly cost-effective in improving neonatal survival and have a very favourable return on investment. The intervention can be scaled up in similar settings within India and other countries.