bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stressed-Out Oral Immunity: A Gateway From Socioeconomic Adversity to Periodontal Disease
Authors: Gomaa Noha , Glogauer Michael , Nicolau Belinda , Tenenbaum Howard , Siddiqi Arjumand , Fine Noah , Quiñonez Carlos 
Published: December 2019

ABSTRACT

Objective
It has been suggested that adverse socioeconomic conditions “get under the skin” by eliciting a stress response that can trigger periodontal inflammation. We aimed to a) estimate the extent to which socioeconomic position (SEP) is associated with periodontal disease (PD) and proinflammatory oral immunity, and b) determine the contribution of psychosocial stress and stress hormones to these relationships.

Methods
In this cross-sectional study (n = 102), participants (20–59 years old) completed financial and perceived stress questionnaires and underwent full-mouth periodontal examinations. SEP was characterized by annual household income and educational attainment. Cortisol, a biological correlate of chronic stress, was assessed in hair samples. Oral immunity was characterized by assessing oral inflammatory load and proinflammatory oral neutrophil function. Blockwise Poisson and logistic regression models were applied.

Results
Compared with lower SEP, individuals in the middle- and higher-income categories had a significantly lower probability of PD (incidence rate ratio [IRR] = 0.5 [confidence interval {CI} = 0.3–0.7] and IRR = 0.4 [95% CI = 0.2–0.7]) and oral inflammatory load (IRR = 0.6 [95% CI = 0.3–0.8] and IRR = 0.5 [95% CI = 0.3–0.7]) and were less likely to have a proinflammatory oral immune function (odds ratio [OR] = 0.1 [95% CI = 0.0–0.7] and OR = 0.1 [95% CI = 0.0–0.9]). PD and oral immune parameters were significantly associated with financial stress and cortisol. Adjusting for financial stress and cortisol partially attenuated the socioeconomic differences in PD to IRR = 0.7 (95% CI = 0.5–0.8) and IRR = 0.6 (95% CI = 0.5–0.7) for the middle- and higher-income categories, respectively. Similar results were observed for proinflammatory immunity (OR = 0.2 [95% CI = 0.0–1.8] and OR = 0.3 [95% CI = 0.0–2.3]).

Conclusion
These findings suggest that psychosocial stress may contribute to a proinflammatory immunity that is implicated in PD pathobiology and provide insight into social-to-biological processes in oral health.
A Comparative Study on the Effects of High-Intensity Focused Electromagnetic Technology and Electrostimulation for the Treatment of Pelvic Floor Muscles and Urinary Incontinence in Parous Women: Analysis of Posttreatment Data
Authors: Silantyeva Elena , Zarkovic Dragana , Astafeva Evgeniia , Soldatskaia Ramina , Orazov Mekan , Belkovskaya Marina , Kurtser Mark ,   Academician of the Russian Academy of Sciences
Published: December 2019

Objectives
Pelvic floor muscles (PFMs) weakening and urinary incontinence (UI) represent health issues that have a negative impact on daily life. This study compares the immediate efficiency of high-intensity focused electromagnetic (HIFEM) therapy and electrostimulation for the treatment of weakened PFMs, accompanied by the UI.

Methods
Ninety-five parous women were considered for the study. Symptomatic patients received either HIFEM or electrostimulation treatment. Treated patients completed 10 therapies scheduled 2 to 3 times per week (HIFEM) or every other day (electrostimulation). Patients underwent examination by 3-dimensional transperienal ultrasound at the baseline and posttreatments. Levator-urethra gap, anteroposterior diameter, laterolateral diameter of levator hiatus, and hiatal area were measured. In addition, Pelvic Floor Disability Index 20 questionnaire and subjective evaluation of patient’s intimate health were assessed.

Results
Enrolled patients were divided into group I (n = 50, HIFEM), group II (n = 25, electrostimulation), and group III (n = 20, control) according the indication and treatment modality. Three-dimensional ultrasounds showed positive changes in dynamics of the pelvic floor posttreatment (decreased anteroposterior diameter, laterolateral diameter, and hiatal area). However, the significant (P < 0.05) changes of pelvic floor integrity were observed only in group I. In addition, group I achieved greater level of improvement in Pelvic Floor Disability Index 20 questionnaire compared with group II (52% and 18% respectively; P < 0.001). Substantially fewer patients in group I reported urine leakage after treatments.

Conclusions
Posttreatment results suggest that HIFEM technology is suitable for treatment of PFMs weakening and showed to be more effective when compared with electrostimulation in short-term. Therefore, we recommend HIFEM as treatment option for weakened PFMs and UI.
Mechanical model of muscle contraction. 1. Force-velocity relationship
Authors: Louvet S. 
Published: December 2019

AbstractThe two parameters that determine the functionality of a skeletal muscle fiber are the tension (T) exerted at its two endpoints and the shortening speed (V), two mechanical characteristics. We established a relationship between T and V by developing a theoretical model of muscle contraction based on the swinging lever arm hypothesis. At the nanoscale, force and movement are generated by the myosin II heads during the working stroke (WS). The change in conformation of a myosin head during the WS is characterized by the rotation of the lever correlated to the linear displacement of the motor domain. The position of the lever is marked by the angle θ. The maximum variation of θ between the two limits θupand θdownrelating to the two positionsupanddownis usually given equal to 70°. When the angle θ is between θupand θdown, the WS is triggered in three modes, fast, slow or very slow. During the isometric tetanus plateau, θ is uniformly distributed between the two angles θup and θTseparated by a usual difference of 50°. Consequently during isometric tetanus plateau there is a 20° interval between θTand θdownwhere no head is found in WS. We link this absence to the slow detachment of the heads whose orientation of the levers is between θTand θdownduring the rise to the isometric tetanus plateau. The equation between T and V refers to these four occurrences: fast, slow or very slow initiations of the WS between θupand θdown, then slow detachment between θTand θdown. The equation is constructed from the geometric data of the myosin head and the time constants of the cross-bridge cycle reactions associated with these four events. The biphasic aspect of the curve is explained by the slow detachment that occurs only at very slow speeds. An additional term, derived from the viscosity present as soon as the velocity increases completes the equation. An adequate fit between the model and examples from the physiological literature is found (r2> 99%).
Mechanical model of muscle contraction. 5. Tension rise after phase 1 of a length step
Authors: Louvet S. 
Published: December 2019

AbstractThe theoretical approaches developed in accompanying Papers 1 to 3 lead to calculations of the isometric tetanus tension (T0) and the minimum tension (T1) observed at the end of phase 1 of a length step where the fiber is shortened (see Paper 4). During the next three phases, the time rise of the tension (T), from T1 to T0, is determined for any step (see Supplement S5.K). The tension T is expressed as a master equation which is the sum of five terms: (a) T1, (b) a positive or zero contribution resulting from the relaxation induced by the disappearance of the viscosity forces present during phase 1, (c) a positive contribution of elastic origin resulting from the new myosin II heads initiating a working stroke (WS) in the blank areas, (d) a negative contribution caused by the fast detachment of the heads still strongly attached and whose orientation of the levers is beyond theupposition, (e) a negative contribution caused by the slow detachment of WS heads whose orientation of the levers is close to theupposition. An agreement between the model equation and the experimental results referenced in the physiological literature is proven (r2>97.5%). The kinetics of each of the theoretical curves make it possible to distinguish phases 2, 3 and 4 characteristics of the tension rise to T0. The criteria defined to describe the tension at the end of phase 2 (T2) are applied to the master equation. There is an adequate adjustment between the theoretical and experimental T2 values for shortenings less than 8 nm in modulus (r2> 97%).
Correction of amyotrophic lateral sclerosis related phenotypes in induced pluripotent stem cell-derived motor neurons carrying a hexanucleotide expansion mutation inC9orf72by CRISPR/Cas9 genome editing using homology-directed repair
Authors: Ababneh Nidaa , Scaber Jakub , Flynn Rowan , Douglas Andrew , Turner Martin R. , Sims David , Dafinca Ruxandra , Cowley Sally A. , Talbot Kevin 
Published: December 2019

AbstractThe G4C2 hexanucleotide repeat expansion (HRE) inC9orf72is the commonest cause of familial amyotrophic lateral sclerosis (ALS). A number of different methods have been used to generate isogenic control lines using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 and non-homologous end-joining (NHEJ) by deleting the repeat region with the risk of creating indels and genomic instability. In this study we demonstrate complete correction of an induced pluripotent stem cell (iPSC) line derived from aC9orf72-HRE positive ALS/FTD patient using CRISPR/Cas9 genome editing and homology directed repair (HDR), resulting in replacement of the excised region with a donor template carrying the wild-type repeat size to maintain the genetic architecture of the locus. The isogenic correction of theC9orf72HRE restored normal expression and methylation at the C9orf72 locus, reduced intron retention in the edited lines, and abolished pathological phenotypes associated with theC9orf72HRE expansion in iPSC derived motor neurons (iPSMNs).RNA sequencing of the mutant line identified 2220 differentially expressed genes compared to its isogenic control. Enrichment analysis demonstrated an over-representation of ALS relevant pathways, including calcium ion dependent exocytosis, synaptic transport and the KEGG ALS pathway, as well as new targets of potential relevance to ALS pathophysiology.Complete correction of theC9orf72HRE in iPSMNs by CRISPR/Cas9 mediated HDR provides an ideal model to study the earliest effects of the hexanucleotide expansion on cellular homeostasis and the key pathways implicated in ALS pathophysiology.
QuAdTrim: Overcoming computational bottlenecks in sequence quality control
Authors: Robinson Andrew J. , Ross Elizabeth M. 
Published: December 2019

AbstractWith the recent torrent of high throughput sequencing (HTS) data the necessity for highly efficient algorithms for common tasks is paramount. One task for which the basis for all further analysis of HTS data is initial data quality control, that is, the removal or trimming of poor quality reads from the dataset. Here we present QuAdTrim, a quality control and adapter trimming algorithm for HTS data that is up to 57 times faster and uses less than 0.06% of the memory of other commonly used HTS quality control programs. QuAdTrim will reduce the time and memory required for quality control of HTS data, and in doing, will reduce the computational demands of a fundamental step in HTS data analysis. Additionally, QuAdTrim impliments the removal of homopolymer Gs from the 3’ end of sequence reads, a common error generated on the NovaSeq, NextSeq and iSeq100 platforms.Availability and ImplementationThe source code is freely available on bitbucket under a BSD licence, see COPYING file for details:https://bitbucket.org/arobinson/quadtrimContactAndrew Robinson andrewjrobinson at gmail dot com
Flood-pulse disturbances as a threat for long-living Amazonian trees
Authors: Resende Angélica F , Piedade Maria T F , Feitosa Yuri O , Andrade Victor Hugo F , Trumbore Susan E , Durgante Flávia M , Macedo Maíra O , Schöngart Jochen 
Published: December 2019

AbstractThe long-living tree speciesEschweilera tenuifolia(O. Berg) Miers (Lecythidaceae) is characteristic to oligotrophic floodplain forests (igapó) influenced by a regular and predictable flood-pulse. This species preferentially occurs at macrohabitats flooded up to 10 months per year forming monodominant stands. We aimed to analyze the growth and mortality patterns of this species under pristine conditions (Jaú National Park-JNP) and in an impactedigapó(Uatumã Sustainable Development Reserve-USDR) where the downstream flood-pulse disturbance occasioned by the Balbina hydroelectric plant caused massive mortality of this species. Using a total of 91 trees (62 living and 29 dead) at the USDR and 52 (31 living and 21 dead) from JNP, we analyzed age-diameter relationships, mean passage time through 5-cm diameter classes, growth change patterns, growth ratios, clustering of mean diameter increment (MDI), and dated the year of death from each individual using radiocarbon (14C) analysis. Growth and mortality patterns were then related to climatic or anthropogenic disturbances. Our results show similar structural parameters for both studied populations regarding the estimated maximum ages of 466 years (JNP) and 498 years (USDR) and MDI, except for one single tree at the USDR with an estimated age of 820 yrs. Living trees from JNP showed distinctly altered growth after 1975, probably related to consecutive years of high annual minimum water levels. Tree mortality in the JNP occurred during different periods, probably induced by extreme hydroclimatic events. At the USDR changes in growth and mortality patterns occurred after 1983, when the Balbina dam construction started. Despite being one of the best flood-adapted tree species,E. tenuifoliaseems to be sensitive to both, long-lasting dry and wet periods induced by climatic or anthropogenic disturbances or resulting synergies among both. Even more than 30 years after the start of disturbances at the USDR, the flood-pulse alteration continues affecting both mortality and growth of this species which can potentially cause regional extinction.
Mucin hydrogel glyco-modulation to investigate immune activity of mucin glycans
Authors: Yan Hongji , Hjorth Morgan , Winkeljann Benjamin , Dobryden Illia , Lieleg Oliver , Crouzier Thomas 
Published: December 2019

AbstractMucins are multifunctional glycosylated proteins that are increasingly investigated as building blocks of novel biomaterials. Once assembled into hydrogels (Muc gels), mucins were shown to modulate the recruitment and activation of immune cells and avoid fibrous encapsulationin vivo. However, nothing is known about the early immune response to Muc gels. This study characterizes the response of macrophages, important orchestrators of the material-mediated immune response, over the first 7 days in contact with Muc gels. The role of mucin-bound sialic acid sugar residues was investigated by first enzymatically cleaving the sugar, then assembling the mucin variants into covalently crosslinked hydrogels with rheological and surface nanomechanical properties similar to non-modified Muc gels. Results with THP1 and human primary peripheral blood monocytes-derived macrophages were strikingly consistent and showed that Muc gels transiently activate the expression of both pro-inflammatory and anti-inflammatory cytokines and cell surface markers, with a maximum on the first day and loss of the effect after 7 days. The activation was sialic acid-dependent for a majority of the markers followed. The pattern of gene expression, protein expression, and functional measurements did not strictly correspond to M1 or M2 macrophage phenotypes. This study highlights the complex early events in macrophage activation in contact with mucin materials and the importance of sialic acid residues in such a response. The enzymatic glyco-modulation of Muc gels appears as a useful tool to help understand the biological functions of specific glycans on mucins which can further inform on their use in various biomedical applications.
Ignoring correlated activity causes a failure of retinal population codes under moonlight conditions
Authors: Ruda Kiersten , Zylberberg Joel , Field Greg D. 
Published: December 2019

AbstractThe retina encodes visual stimuli across light intensities spanning 10-12 orders of magnitude from starlight to sunlight. To accommodate this enormous range, adaptation alters retinal output, changing both the signal and noise among populations of retinal ganglion cells (RGCs). Here we determine how these light level-dependent changes in signal and noise impact decoding of retinal output. In particular, we consider the importance of accounting for noise correlations among RGCs to optimally read out retinal activity. We find that at moonlight conditions, correlated noise is greater and assuming independent noise severely diminished decoding performance. In fact, assuming independence among a local population of RGCs produced worse decoding than using a single RGC, demonstrating a failure of population codes when correlated noise is substantial and ignored. We generalize these results with a simple model to determine the signal and noise conditions under which this failure of population processing can occur. This work elucidates the circumstances in which accounting for noise correlations is necessary to take advantage of population-level codes and shows that sensory adaptation can strongly impact decoding requirements on downstream brain areas.
Chromatin regulatory dynamics of early human small intestinal development using a directed differentiation model
Authors: Hung Yu-Han , Huang Sha , Dame Michael K. , Yu Qianhui , Yu Qing Cissy , Zeng Yi Arial , Camp J. Gray , Spence Jason R. , Sethupathy Praveen 
Published: December 2019

AbstractBackgroundThe establishment of the small intestinal (SI) lineage during human embryogenesis is critical for the proper development of neonatal gut functions, including nutrient absorption and immune defense. The chromatin dynamics and regulatory networks that drive human SI lineage formation and regional patterning are essentially unknown. To fill this knowledge void, we apply a cutting-edge genomic technology to a state-of-the-art human model of early SI development. Specifically, we leverage chromatin run-on sequencing (ChRO-seq) to define the landscape of active promoters, enhancers, super enhancers, and gene bodies across distinct stages of directed differentiation of human pluripotent stem cells (hPSCs) into SI spheroids with regional specification.ResultsThrough comprehensive ChRO-seq analysis we identify candidate stage-specific chromatin activity states, novel markers, and enhancer hotspots during the directed differentiation process. Moreover, we propose a detailed transcriptional network associated with SI lineage formation or initial regional patterning. Among our findings is a unique pattern of enhancer activity and transcription at HOX gene loci that is previously undescribed. Analysis of single cell RNA-seq data from human fetal SI at early developmental time points shed further light on the unique HOX gene temporal dynamics that underlies SI regional patterning.ConclusionsOverall, the results lead to a new proposed working model for the regulatory underpinnings of human SI lineage formation and regional patterning, thereby adding a novel dimension to the literature that has thus far relied almost exclusively on non-human models.
Compensatory mutation can drive gene regulatory network evolution
Authors: Wang Yifei , Richards Marios , Dorus Steve , Priest Nicholas K. , Bryson Joanna J. 
Published: December 2019

AbstractGene regulatory networks underlie every aspect of life; better understanding their assembly would better our understanding of evolution more generally. For example, evolutionary theory typically assumed that low-fitness intermediary pathways are not a significant factor in evolution, yet there is substantial empirical evidence of compensatory mutation. Here we revise theoretical assumptions to explore the possibility that compensatory mutation may drive rapid evolutionary recovery. Using a well-establishedin silicomodel of gene regulatory networks, we show that assuming only that deleterious mutations are not fatal, compensatory mutation is surprisingly frequent. Further, we find that it entails biases that drive the evolution of regulatory pathways. In our simulations, we find compensatory mutation to be common during periods of relaxed selection, with 8-15% of degraded networks having regulatory function restored by a single randomly-generated additional mutation. Though this process reduces average robustness, proportionally higher robustness is found in networks where compensatory mutations occur close to the deleterious mutation site, or where the compensatory mutation results in a large regulatory effect size. This location- and size-specific robustness systematically biases which networks are purged by selection for network stability, producing emergent changes to the population of regulatory networks. We show that over time, large-effect and co-located mutations accumulate, assuming only that episodes of relaxed selection occur, even very rarely. This accumulation results in an increase in regulatory complexity. Our findings help explain a process by which large-effect mutations structure complex regulatory networks, and may account for the speed and pervasiveness of observed occurrence of compensatory mutation, for example in the context of antibiotic resistance, which we discuss. If sustained byin vitroexperiments, these results promise a significant breakthrough in the understanding of evolutionary and regulatory processes.
Periphilin self-association underpins epigenetic silencing by the HUSH complex
Authors: Prigozhin Daniil M. , Albecka Anna , Douse Christopher H. , Tchasovnikarova Iva A. , Timms Richard T. , Farleigh Laura E. , Oda Shun , Freund Stefan M. V. , Maslen Sarah , Lehner Paul J. , Modis Yorgo 
Published: December 2019

AbstractTranscription of integrated DNA from viruses or transposable elements is tightly regulated to prevent pathogenesis. The Human Silencing Hub (HUSH), composed of Periphilin, TASOR and MPP8, silences transcriptionally active viral and endogenous transgenes. HUSH recruits effectors that alter the epigenetic landscape and chromatin structure, but how HUSH recognizes target loci and represses their expression remains unclear. We identify the physicochemical properties of Periphilin necessary for HUSH assembly and silencing. A disordered N-terminal domain (NTD) and structured C-terminal domain are essential for silencing. A crystal structure of the Periphilin-TASOR core complex shows Periphilin formsα-helical homodimers, which each bind a single TASOR molecule. The NTD binds RNA non-specifically and forms insoluble aggregates through an arginine/tyrosine-rich sequence reminiscent of low-complexity regions from self-associating RNA-binding proteins. Residues required for TASOR binding and aggregation were required for HUSH-dependent silencing and genome-wide deposition of repressive mark H3K9me3. The NTD was functionally complemented by low-complexity regions from certain RNA-binding proteins and proteins that form condensates or fibrils. Our work suggests the associative properties of Periphilin promote HUSH aggregation on nascent transcripts.