bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization and engineering of S100A12–heparan sulfate interactions
Authors: Zhang Xiaoxiao , Ong Chihyean , Su Guowei , Liu Jian , Xu Ding
Published: December 2019

S100A12, an EF-hand calcium-binding protein, can be secreted by a variety of cell types and plays proinflammatory roles in a number of pathological conditions. Although S100A12 has been shown to interact with heparan sulfate (HS), the molecular detail of the interaction remains unclear. Here we investigate the structural basis of S100A12–HS interaction and how the interaction is regulated by the availability of divalent cations and the oligomeric states of S100A12. We discovered that S100A12–HS interaction requires calcium, while zinc can further enhance binding by inducing S100A12 hexamerization. In contrast, the apo form and zinc-induced tetramer form were unable to bind HS. Guided by the crystal structures of S100A12, we have identified the HS-binding site of S100A12 by site-directed mutagenesis. Characterization of the HS-binding site of S100A12 allowed us to convert the non-HS-binding apo and tetramer forms of S100A12 into a high affinity HS-binding variant by engineering a single-point mutation. Using a HS oligosaccharide microarray, we demonstrated that the N43K mutant displayed markedly enhanced selectivity toward longer HS oligosaccharides compared to the WT S100A12, likely due to the expanded dimension of the reengineered HS-binding site in the mutant. This unexpected finding strongly suggests that HS-binding sites of proteins might be amenable for engineering.
Has the prevalence of overweight, obesity and central obesity levelled off in the United States? Trends, patterns, disparities, and future projections for the obesity epidemic
Authors: Wang Youfa , Beydoun May A , Min Jungwon , Xue Hong , Kaminsky Leonard A , Cheskin Lawrence J
Published: December 2019

Background

Obesity (OB) is a serious epidemic in the United States.

Methods

We examined OB patterns and time trends across socio-economic and geographic parameters and projected the future situation. Large national databases were used. Overweight (OW), OB and severe obesity (SOB) were defined using body mass index cut-points/percentiles; central obesity (CO), waist circumference cut-point in adults and waist:height ratio cutoff in youth. Various meta-regression analysis models were fit for projection analyses.

Results

OB prevalence had consistently risen since 1999 and considerable differences existed across groups and regions. Among adults, men’s OB (33.7%) and OW (71.6%) levelled off in 2009–2012, resuming the increase to 38.0 and 74.7% in 2015–2016, respectively. Women showed an uninterrupted increase in OB/OW prevalence since 1999, reaching 41.5% (OB) and 68.9% (OW) in 2015–2016. SOB levelled off in 2013–2016 (men: 5.5–5.6%; women: 9.7–9.5%), after annual increases of 0.2% between 1999 and 2012. Non-Hispanic Blacks had the highest prevalence in women’s OB/SOB and men’s SOB. OB prevalence in boys rose continuously to 20.6% and SOB to 7.5% in 2015–2016, but not in girls. By 2030, most Americans will be OB/OW and nearly 50% of adults OB, whereas ∼33% of children aged 6–11 and ∼50% of adolescents aged 12–19 will be OB/OW. Since 1999, CO has risen steadily, and by 2030 is projected to reach 55.6% in men, 80.0% in women, 47.6% among girls and 38.9% among boys. Regional differences exist in adult OB prevalence (2011–2016) and across ethnicities; South (32.0%) and Midwest (31.4%) had the highest rates.

Conclusions

US obesity prevalence has been rising, despite a temporary pause in 2009–2012. Wide disparities across groups and geographical regions persist. Effective, sustainable, culturally-tailored interventions are needed.
Scale-invariant dynamics of galaxies, MOND, dark matter, and the dwarf spheroidals
Authors: Maeder Andre , Gueorguiev Vesselin G
Published: December 2019

The Scale-Invariant Vacuum (SIV) theory is based on Weyl’s Integrable Geometry, endowed with a gauge scalar field. The main difference between MOND and the SIV theory is that the first considers a global dilatation invariance of space and time, where the scale factor λ is a constant, while the second opens the likely possibility that λ is a function of time. The key equations of the SIV framework are used here to study the relationship between the Newtonian gravitational acceleration due to baryonic matter gbar and the observed kinematical acceleration gobs. The relationship is applied to galactic systems of the same age where the radial acceleration relation (RAR), between the gobs and gbar accelerations, can be compared with observational data. The SIV theory shows an excellent agreement with observations and with MOND for baryonic gravities gbar > 10−11.5 m s−2. Below this value, SIV still fully agrees with the observations, as well as with the horizontal asymptote of the RAR for dwarf spheroidals, while this is not the case for MOND. These results support the view that there is no need for dark matter and that the RAR and related dynamical properties of galaxies can be interpreted by a modification of gravitation.
Violent buckling benefits galactic bars
Authors: Collier Angela
Published: December 2019

Galactic bars are unstable to a vertical buckling instability which heats the disc and in some cases forms a boxy/peanut shaped bulge. We analyse the buckling instability as an application of classical Euler buckling followed by non-linear gravitational Landau damping in the collisionless system. We find that the buckling instability is dictated by the kinematic properties and geometry of the bar. The analytical result is compared to simulations of isolated galaxies containing the disc and dark matter components. Our results demonstrate that violent buckling does not destroy bars while a less energetic buckling can dissolve the bar. The discs that undergo gentle buckling remain stable to bar formation which may explain the observed bar fraction in the local Universe. Our results align with the results from recent surveys.
Integrating Music Therapy Students into Interprofessional Education: Academic Program Development
Authors: Meadows Anthony , Schempp Anne , Landless Bronwen
Published: December 2019

Interprofessional education (IPE) occurs when students from two or more professions associated with health or social care engage in learning with, from, and about each other. IPE addresses four essential competencies that not only seek to prepare students for interprofessional practice, but also strive to improve the overall quality of healthcare delivery for patients and their families. This article describes the development of an IPE program that fully integrates music therapy students into program-wide and program-to-program IPE events. We identify core components of IPE, describe the development of program-wide and program-to-program events involving undergraduate and graduate music therapy students, and discuss the benefits and challenges encountered during program development. In doing so, we advocate for IPE as a core component of music therapy education and training.
Risks and Safety of Extended Auricular Therapy: A Review of Reviews and Case Reports of Adverse Events
Authors: Nielsen Arya , Gereau Sezelle , Tick Heather
Published: December 2019

Objective

Auricular acupuncture (AA) and extended auricular therapy (AT) are a part of acupuncture practice shown to benefit patients with pain, anxiety, and other conditions, with cost-effective access enhanced when given in a group setting. Yet there are safety concerns and risks, perhaps unnecessary risks, that attend embedded, indwelling needles applied to the ear as a means of extended AT.

Methods

Electronic searches were conducted in PubMed, MEDLINE, CINAHL and Cochrane Central Register of Controlled Trials (CENTRAL) for “auriculotherapy,” “auricular acupuncture” or “auricular acupressure,” “safety,” “adverse events,” “chondritis,” and “perichondritis,” with additional manual review of titles, links, and reference lists. Individual auricular therapy adverse event (AE) case reports were included, as well as systematic reviews and or meta-analyses if they evaluated AEs associated with AT.

Results

Nineteen auricular AE case reports and nine safety reviews of or including auriculotherapy were included. Ten systematic reviews of AT with eight specific reviews of auricular acupressure (AP) were also included.

Conclusions

The primary AE risks is infection, perichondritis, and chondritis stemming from embedded or indwelling needles or potential inadvertent needlesticks from contaminated roaming sharps. Extended AP i.e., application of spheres, preferably seeds (natural, nontoxic botanical Vaccaria seeds) provides clinical benefit without the risks associated with embedded needles. More research is needed to establish if embedded needles at the ear are even necessary or have any advantage over in-session auricular acupuncture for immediate pain relief followed by ear acupressure.
SYMMETRIC MONOIDALG-CATEGORIES AND THEIR STRICTIFICATION
Authors: Guillou Bertrand J , May J Peter , Merling Mona , Osorno Angélica M
Published: December 2019

We give an operadic definition of a genuine symmetric monoidal $G$-category, and we prove that its classifying space is a genuine $E_\infty $$G$-space. We do this by developing some very general categorical coherence theory. We combine results of Corner and Gurski, Power and Lack to develop a strictification theory for pseudoalgebras over operads and monads. It specializes to strictify genuine symmetric monoidal $G$-categories to genuine permutative $G$-categories. All of our work takes place in a general internal categorical framework that has many quite different specializations. When $G$ is a finite group, the theory here combines with previous work to generalize equivariant infinite loop space theory from strict space level input to considerably more general category level input. It takes genuine symmetric monoidal $G$-categories as input to an equivariant infinite loop space machine that gives genuine $\Omega $-$G$-spectra as output.
IgG4-related disease: a clinical perspective
Authors: Maritati Federica , Peyronel Francesco , Vaglio Augusto
Published: December 2019

IgG4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory disorder that can affect almost any organ. Common presentations include major salivary and lacrimal gland enlargement, orbital disease, autoimmune pancreatitis, retroperitoneal fibrosis and tubulointerstitial nephritis. The main histopathological features are a dense, polyclonal, lymphoplasmacytic infiltrate rich in IgG4+ plasma cells, storiform fibrosis and obliterative phlebitis. The precise pathogenic mechanisms of IgG4-RD are still unclear. CD4+ T and B cells, including IgG4-expressing plasmablasts, constitute the major inflammatory cell populations and are believed to cause organ damage and tissue fibrosis. The diagnosis of the disease may be challenging and should be based on specific histopathological findings, typical laboratory and radiological aspects and an appropriate clinical context. The first-line treatment of IgG4-RD is based on glucocorticoids, which are usually efficacious. However, B cell depletion induced by rituximab has also been found to induce remission in steroid-resistant disease or has been used as steroid-sparing agent for relapsing disease. This review provides an update on clinical and therapeutic aspects of IgG4-RD.
Facilitators of peer coaching/support engagement and dissemination among women at risk for and surviving with breast cancer
Authors: Rehberg Kathryn , Fleischmann Adina , Silber Elana , O’neill Suzanne C , Lewis Frances Marcus , Tercyak Kenneth P
Published: December 2019

One-on-one peer coaching/support programs hold promise in promoting healthy outcomes among women at risk for and surviving with breast cancer, with the potential to bridge gaps in “whole person care.” Although popularly cited for their benefits, emerging evidence is mixed and suggests that peer support program impacts may be attenuated by individual- and community-specific factors. We evaluated a national not-for-profit breast cancer organization’s peer support program outcomes (2015–2018) serving women from predominantly Jewish backgrounds to examine program engagement, facilitation, and satisfaction. Of the N = 392 women sampled, 37% utilized the peer support program: the majority were referred by a family member/friend (40%) or had connected with the program online (34%). Logistic regression modeling revealed that mothers (odds ratio [OR] = 1.82; 95% confidence interval [CI] = 1.04 to 3.19), women at increased genetic risk for breast cancer (OR = 2.07; 95% CI = 1.08 to 3.94), and those who connected with the organization through a family member/friend (OR = 1.97; 95% CI = 1.23 to 3.15) were significantly more likely to utilize peer support (all p’s < .05). Satisfaction with peer support was high and reliably measured (M = 42.8 out of possible 50; α = .95). These findings emphasize opportunities for peer support programs to serve a range of needs among breast cancer previvors and survivors and increase health care’s organizational capacity to reach and impact this community through trusted and well-trained lay coaches.
Tumor uptake and associated greater efficacy of anti-Her2 immunoliposome does not rely on Her2 expression status: study of a docetaxel-trastuzumab immunoliposome on Her2+ breast cancer model (SKBR3)
Authors: Rodallec Anne , Sicard Guillaume , Giacometti Sarah , Carre Manon , Maia Thomas , Valette Margaux , Bouquet Fanny , Savina Ariel , Lacarelle Bruno , Ciccolini Joseph , Fanciullino Raphaelle
Published: December 2019

Nanoparticles have been used for decades in breast cancer. More recently, anti-human epidermal receptor 2 (Her2) immunoliposomes are of rising interest. However, recent studies have questioned the actual relevance of using anti-Her2 antibodies to improve liposome distribution and efficacy. Using standard thin-film method and maleimide linker, we have synthesized a 140-nm docetaxel-trastuzumab immunoliposome. This nanoparticle was then tested on a canonical Her2-overexpressing breast cancer model (i.e., SKBR3), using 3D spheroids and xenografted mice. Its efficacy was compared with free docetaxel + trastuzumab, liposomal docetaxel + free trastuzumab and to reference antibody-drug conjugate trastuzumab-emtansine (T-DM1). Immunoliposomes resulted in better efficacy as compared with all other treatments, both in vitro and in vivo. To explain such an improvement, immunoliposome biodistribution was investigated using live imaging in xenografted mice. Surprisingly, no difference in tumor uptake was found between anti-Her2 immunoliposomes and standard docetaxel liposomes (i.e., 1.9 ± 1.2 vs. 1.7 ± 0.5% at the end of treatment and 1.4 ± 0.6 vs. 1.6 ± 0.4% at the end of the study, respectively, P > 0.05). We hypothesized that passive targeting (i.e., enhanced permeation and retention effect) contributed more to tumor distribution than active targeting and that the observed differences in efficacy could come from a better internalization of immunoliposomes into Her2+ cells as compared with standard liposomes, and not from a higher specificity towards tumor tissue.
Intimidation and Sexual Harassment during Plastic Surgery Training in the United States
Authors: D’Agostino Johanna P. , Vakharia Kavita T. , Bawa Sheina , Sljivic Sanja , Natoli Noel
Published: December 2019

Background:

Attending physicians, peers, other providers, and patients are sources of intellectual growth, but may also be a source of abuse and harassment. Published international studies have found that harassment within residency training is widespread but there is little data regarding plastic surgery training. The authors sought to explore the incidence of harassment experienced by plastic surgery residents currently enrolled in US integrated and independent programs.

Methods:

After an IRB-approved exemption was obtained, an anonymous internet-based survey was distributed via email to all plastic and reconstructive surgery residency programs. The survey was comprised of 23 questions that focused on personal experience or knowledge of other colleagues who had encountered abuse and harassment during their training. Responses were collected during a 60-day period. The response rate was 16%.

Results:

A total of 173 individuals completed the survey. Regarding harassment experienced by the respondents, 39.2% reported verbal abuse, 19.9% experienced sexual harassment, and 3.6% reported being physically abused during their training. Of those individuals who were sexually harassed, 72.7% were females. In many of the cases (64.5%), the instigator was a supervising physician. Most respondents did not feel comfortable reporting the abuse (74.19%).

Conclusions:

Abuse and sexual harassment rates among active plastic and reconstructive surgery residents in the United States are high and attention should be brought to this important issue. Further studies should be conducted to assess the extent of abuse so that it can lead to implementation of programs that provide accountability, improved support, counseling strategies, and foster appropriate professional development.
Single-photon emission computed tomography/computed tomography arthrography of wrist, ankle, and knee joints
Authors: Bhure Ujwal , Roos Justus E. , Perez-Lago Maria del Sol , Strobel Klaus
Published: December 2019

Objective

To evaluate the additional value of single-photon emission computed tomography/computed tomography arthrography compared with single-photon emission computed tomography/computed tomography alone in wrist, ankle, and knee joints.

Materials and methods

Retrospective evaluation of 68 patients including 74 joints (48 wrists, 13 upper ankle (talocrural joint), and 13 knee joints) was performed. Activity in single-photon emission computed tomography/computed tomography images was graded using a four-point scale: 0 no uptake, one low uptake, two moderate uptake, and three high uptake. Arthrography images were evaluated for the presence of cartilage/ligament/meniscal lesions, and loose bodies.

Results

Fifty-six joints (76%) showed increased activity in late planar and 58 (78%) in single-photon emission computed tomography/computed tomography images, the latter graded as follows: grade 1 in 20 (34%), grade 2 in 29 (50%), grade 3 in nine (16%) joints. 16 joints were inactive (grade 0) in single-photon emission computed tomography/computed tomography. In 57 joints (77%), intraarticular contrast unmasked additional pathologies (37 cartilage lesions, 25 ligaments tears, 25 triangular fibrocartilage complex tears, six meniscal lesions, and four loose bodies). There was matching findings between single-photon emission computed tomography and computed tomography arthrography in 57 joints (77%) and mismatching findings in 17 joints (23%). Out of these 17 mismatched joints, eight were metabolically inactive but showed some lesion in computed tomography arthrography, whereas nine metabolically active joints did not show any abnormality in computed tomography arthrography.

Conclusion

The addition of arthrography to single-photon emission computed tomography/computed tomography of wrist, ankle, and knee joints leads to supplementary visibility of lesions of cartilage, ligaments, triangular fibrocartilage complex, meniscus, or loose bodies in 77% of joints. Single-photon emission computed tomography/computed tomography arthrography can serve as promising alternative especially in patients with magnetic resonance imaging contraindications or metallic hardware.
Cancer cachexia: a multifactoral disease that needs a multimodal approach
Authors: Stubbins Renee , Bernicker Eric H. , Quigley Eamonn M.M.
Published: December 2019

Purpose of review

Cancer cachexia is a complex condition that occurs in approximately 50% of cancer patients and in 80% of those with advanced cancer. It is characterized by lean body mass loss, adipose tissue loss, altered metabolism, increased inflammation, and a decrease in quality of life. Cancer cachexia is a frustrating condition to manage and treatment requires an innovative approach. The purpose of this article is to review the current treatments for cancer cachexia and how they could be used in a multimodal approach.

Recent findings

Cancer cachexia has many causes, but is primarily a result of reduced energy-protein intake and altered metabolism augmented by a proinflammatory state. There is not a formal consensus on diagnosing cancer cachexia, but proactive screening and assessments for malnutrition are an effective first step toward identifying high-risk patients. Treatment of cancer cachexia includes optimizing nutrition care, using appropriate pharmacological agents, preserving lean body mass, and the cooperation of the healthcare team.

Cancer cachexia is a complex multifactorial condition that can only be successfully managed and treated with a multimodal approach that involves a multidisciplinary team that includes an oncology registered dietitian nutritionist and exercise physiologist that target early detection and management of cancer cachexia.
Hypomethylating agents with venetoclax: have we discovered the holy grail?
Authors: Gutman Jonathan A. , Pollyea Daniel A.
Published: December 2019

Purpose of review

Since its approval in November 2018, venetoclax with a hypomethylating agent backbone has shown promising efficacy for older, newly diagnosed acute myeloid leukemia (AML) patients who are unfit for standard intensive induction chemotherapy. This regimen is well tolerated, allows for deep and durable responses and may be increasing the prevalence of the disease. Although there is justifiable excitement, it remains to be seen to what extent venetoclax-based regimens, as they are currently administered, will have a long-term impact on the treatment of AML. This review aims to evaluate the strengths of the regimen that deserve enthusiasm as well as its shortcomings, which should be viewed as opportunities for improvement.

Recent findings

The clinical efficacy as well as the novel mechanism of venetoclax with hypomethylating agents will be described here.

Venetoclax with hypomethylating agents do not represent the holy grail for AML, but this regimen is a promising step in the right direction, and proof of principle that a low-intensity therapy can have a major impact on this disease.
Artificial intelligence: the future of urinary stone management?
Authors: Jahrreiss Victoria , Veser Julian , Seitz Christian , Özsoy Mehmet
Published: December 2019

Purpose of review

To investigate the application of artificial intelligence in the management of nephrolithiasis.

Recent findings

Although rising, the number of publications on artificial intelligence for the management of urinary stone disease is still low. Most publications focus on diagnostic tools and prediction of outcomes after clinical interventions. Artificial intelligence can, however, play a major role in development of surgical skills and automated data extraction to support clinical research.

The combination of artificial intelligence with new technological developments in the field of endourology will create new possibilities in the management of urinary stones. The implication of artificial intelligence can lead to better patient selection, higher success rates, and furthermore improve patient safety.
Whither Research Domain Criteria?
Authors: Dean Charles E.
Published: December 2019

In 2010, the National Institute of Mental Health launched the Research Diagnostic Criteria (RDoC) as a research framework aimed at advancing research into the etiology of mental disorders, the development of clinically actionable biomarkers, and the eventual development of precision medications. The foundation of RDoC in that first phase rested in the assumption that mental disorders are brain disorders that originate in aberrant neural circuitry, and that therapeutic advances could flow from alterations in that circuitry. RDoC proposed a matrix of psychological constructs with seven levels of analysis ranging from the cell to self-report, but with neural circuitry at the center. In 2016, another model was proposed in which neural circuitry became equivalent to other units of analyses. With the advent of a new Director of the NIMH, the emphasis returned to neural circuitry as a priority, along with computational psychiatry. Have these shifts undermined the RDoC project?
Effect of Simulated and Real Spherical and Astigmatism Defocus on Visual Acuity and Image Quality Score
Authors: Vincent Marc , Marin Gildas , Legras Richard
Published: December 2019

SIGNIFICANCE

Image simulation is a useful and efficient tool to explore the impact of spherical and astigmatic blur on visual acuity (VA) and image gradation. It could help to design new optical corrections more efficiently and rapidly.

PURPOSE

The purpose of this study was to compare the effects of simulated (convolution by an artificial eye) and real spherical and astigmatic defocus on VA and image gradation.

METHODS

Experiments were performed under highly controlled conditions: dynamic correction of the subjects' aberrations at 1 Hz and application of an artificial pupil. In experiment 1, Landolt C VA was measured in various conditions of spherical and astigmatism defocus. The amounts of spherical or positive astigmatic defocus oriented at 45° that gives a Landolt C VA of 0.0, 0.2, and 0.5 logMAR were measured in experiment 2. In experiment 3, the subjects scored the quality of the perceived image (three high-contrast 0.4 logMAR letters) with a five-item continuous grading scale.

RESULTS

Simulated blur was always more detrimental than optical blur. We measured a difference of 0.08 ± 0.03 and 0.11 ± 0.05 logMAR between both conditions, respectively, in presence of spherical and astigmatism defocus. An average ± standard deviation difference of 0.16 ± 0.06 D (i.e., spherical defocus) and 0.24 ± 0.15 D (i.e., astigmatism defocus) was observed between simulated and real optics blur to provide a given VA. The differences of image quality score between both conditions were, respectively, 15.13 ± 9.63 and 13.33 ± 4.83 for spherical and astigmatism defocus. Most of the differences were statistically significant.

CONCLUSIONS

We observed a difference of about 20 and 35% between simulated and real optics blur, respectively, in presence of spherical and astigmatism blur. However, the difference between both methods remains equal to or below the clinically significant difference.
The steering gaits of sperm
Authors: Gong A. , Rode S. , Kaupp U. B. , Gompper G. , Elgeti J. , Friedrich B. M. , Alvarez L.
Published: December 2019

Sperm are highly specialized cells, which have been subject to substantial evolutionary pressure. Whereas some sperm features are highly conserved, others have undergone major modifications. Some of these variations are driven by adaptation to mating behaviours or fitness at the organismic level. Others represent alternative solutions to the same task. Sperm must find the egg for fertilization. During this task, sperm rely on long slender appendages termed flagella that serve as sensory antennas, propellers and steering rudders. The beat of the flagellum is periodic. The resulting travelling wave generates the necessary thrust for propulsion in the fluid. Recent studies reveal that, for steering, different species rely on different fundamental features of the beat wave. Here, we discuss some examples of unity and diversity across sperm from different species with a particular emphasis on the steering mechanisms.

This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Multiscale mechanics of mucociliary clearance in the lung
Authors: Nawroth Janna C. , van der Does Anne M. , Ryan (Firth) Amy , Kanso Eva
Published: December 2019

Mucociliary clearance (MCC) is one of the most important defence mechanisms of the human respiratory system. Its failure is implicated in many chronic and debilitating airway diseases. However, due to the complexity of lung organization, we currently lack full understanding on the relationship between these regional differences in anatomy and biology and MCC functioning. For example, it is unknown whether the regional variability of airway geometry, cell biology and ciliary mechanics play a functional role in MCC. It therefore remains unclear whether the regional preference seen in some airway diseases could originate from local MCC dysfunction. Though great insights have been gained into the genetic basis of cilia ultrastructural defects in airway ciliopathies, the scaling to regional MCC function and subsequent clinical phenotype remains unpredictable. Understanding the multiscale mechanics of MCC would help elucidate genotype–phenotype relationships and enable better diagnostic tools and treatment options. Here, we review the hierarchical and variable organization of ciliated airway epithelium in human lungs and discuss how this organization relates to MCC function. We then discuss the relevancy of these structure–function relationships to current topics in lung disease research. Finally, we examine how state-of-the-art computational approaches can help address existing open questions.

This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Neuronal coordination of motile cilia in locomotion and feeding
Authors: Marinković Milena , Berger Jürgen , Jékely Gáspár
Published: December 2019

Efficient ciliary locomotion and transport require the coordination of motile cilia. Short-range coordination of ciliary beats can occur by biophysical mechanisms. Long-range coordination across large or disjointed ciliated fields often requires nervous system control and innervation of ciliated cells by ciliomotor neurons. The neuronal control of cilia is best understood in invertebrate ciliated microswimmers, but similar mechanisms may operate in the vertebrate body. Here, we review how the study of aquatic invertebrates contributed to our understanding of the neuronal control of cilia. We summarize the anatomy of ciliomotor systems and the physiological mechanisms that can alter ciliary activity. We also discuss the most well-characterized ciliomotor system, that of the larval annelidPlatynereis. Here, pacemaker neurons drive the rhythmic activation of cholinergic and serotonergic ciliomotor neurons to induce ciliary arrests and beating. ThePlatynereisciliomotor neurons form a distinct part of the larval nervous system. Similar ciliomotor systems likely operate in other ciliated larvae, such as mollusc veligers. We discuss the possible ancestry and conservation of ciliomotor circuits and highlight how comparative experimental approaches could contribute to a better understanding of the evolution and function of ciliary systems.

This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Multiple merger genealogies in outbreaks ofMycobacterium tuberculosis
Authors: Menardo F. , Gagneux S. , Freund F.
Published: December 2019

The Kingman coalescent and its developments are often considered among the most important advances in population genetics of the last decades. Demographic inference based on coalescent theory has been used to reconstruct the population dynamics and evolutionary history of several species, includingMycobacterium tuberculosis(MTB), an important human pathogen causing tuberculosis. One key assumption of the Kingman coalescent is that the number of descendants of different individuals does not vary strongly, and violating this assumption could lead to severe biases caused by model misspecification. Individual lineages of MTB are expected to vary strongly in reproductive success because 1) MTB is potentially under constant selection due to the pressure of the host immune system and of antibiotic treatment, 2) MTB undergoes repeated population bottlenecks when it transmits from one host to the next, and 3) some hosts show much higher transmission rates compared to the average (“super-spreaders”).

Here we used an Approximate Bayesian Computation approach to test whether multiple merger coalescents (MMC), a class of models that allow for large variation in reproductive success among lineages, are more appropriate models to study MTB populations. We considered eleven publicly available whole genome sequence data sets sampled from local MTB populations and outbreaks, and found that MMC had a better fit compared to the Kingman coalescent for ten of the eleven data sets. These results indicate that the null model for analyzing MTB outbreaks should be reassessed, and that past findings based on the Kingman coalescent need to be revisited.
Genetics of Height and Risk of Atrial Fibrillation: A Mendelian Randomization Study
Authors: Levin Michael G. , Judy Renae , Gill Dipender , Vujkovic Marijana ,   Regeneron Genetics Center, Hyman Matthew C. , Nazarian Saman , Rader Daniel J. , Voight Benjamin F. , Damrauer Scott M.
Published: December 2019

Objective

To determine whether height has a causal effect on risk of atrial fibrillation

Design

Mendelian randomization study

Setting

Genome-wide association studies of height and atrial fibrillation; Penn Medicine Biobank

Participants

Multiethnic (predominantly European ancestry) participants in genome-wide association studies of height (693,529 individuals) and atrial fibrillation (65,446 cases and 522,744 controls); 7,023 Penn Medicine Biobank participants of European ancestry

Exposures

Height, cardiometabolic risk factors for atrial fibrillation, and randomly allocated genetic variants strongly associated with these traits

Main outcome measure

Risk of atrial fibrillation (measured in odds ratio)

Results

At the population level, a 1 standard deviation increase in genetically-predicted height was associated with increased odds of AF (Odds ratio [OR] 1.34; 95% Confidence Interval [CI] 1.29 to 1.40; p = 5×10−42). These findings remained consistent in sensitivity analyses that were robust to the presence of pleiotropic variants. Results from analyses considering individual-participant data were similar, even after adjustment for clinical covariates, including left atrial size.

Conclusion

Genetically predicted height is a positive causal risk factor for AF. This finding raises the possibility of investigating height/growth-related pathways as a means for gaining novel mechanistic insights to atrial fibrillation, as well as incorporating height into population screening strategies for atrial fibrillation.
Effect of Exogenous Amino Acids on Yield and Quality of Tartary Buckwheat in Non-saline and Saline-alkali Soil
Authors: Song Jin-Nan , Wang Ya-Qi , Li Fa-Liang , Hu Yan-Jiang , Yang Hong-Bing
Published: December 2019

Disclaimer Statement

The authors have withdrawn this manuscript (BIORXIV/2019/887778) entitled “Effect of Exogenous Amino Acids on Yield and Quality of Tartary Buckwheat in Non-saline and Saline-alkali Soil” because it requires adding new data and further modifications. Therefore, the authors do not wish this work to be cited (https://www.biorxiv.org/content/10.1101/2019.12.24.887778v5) as reference for the project. If you have any questions, please contact the corresponding author.
Chemical map–based prediction of nucleosome positioning using the Bioconductor package nuCpos
Authors: Kato Hiroaki , Shimizu Mitsuhiro , Urano Takeshi
Published: December 2019

Background

Assessing the nucleosome-forming potential of specific DNA sequences is important for understanding complex chromatin organization. Methods for predicting nucleosome positioning include bioinformatics and biophysical approaches. An advantage of bioinformatics methods, which are based onin vivonucleosome maps, is the use of natural sequences that may contain previously unknown elements involved in nucleosome positioningin vivo. The accuracy of such prediction attempts reflects the genomic coordinate resolution of the nucleosome maps applied. Nucleosome maps are constructed using micrococcal nuclease digestion followed by high-throughput sequencing (MNase-seq). However, as MNase has a strong preference for A/T-rich sequences, MNase-seq may not be appropriate for this purpose. In addition to MNase-seq–based maps, base pair–resolution chemical maps ofin vivonucleosomes from three different species (budding and fission yeasts, and mice) are currently available. However, these chemical maps have yet to be integrated into publicly available computational methods.

Results

We developed a Bioconductor package (named nuCpos) to demonstrate the superiority of chemical maps in predicting nucleosome positioning. The accuracy of chemical map–based prediction in rotational settings was higher than that of the previously developed MNase-seq–based approach. With our method, predicted nucleosome occupancy reasonably matchedin vivoobservations and was not affected by A/T nucleotide frequency. Effects of genetic alterations on nucleosome positioning that had been observed in living yeast cells could also be predicted. nuCpos calculates individual histone binding affinity (HBA) scores for given 147-bp sequences to examine their suitability for nucleosome formation. We also established local HBA as a new parameter to predict nucleosome formation, which was calculated for 13 overlapping nucleosomal DNA subsequences. HBA and local HBA scores for various sequences agreed well with previousin vitroandin vivostudies. Furthermore, our results suggest that nucleosomal subsegments that are disfavored in different rotational settings contribute to the defined positioning of nucleosomes.

Conclusions

Our results demonstrate that chemical map–based statistical models are beneficial for studying nucleosomal DNA features. Studies employing nuCpos software can enhance understanding of chromatin regulation and the interpretation of genetic alterations and facilitate the design of artificial sequences.
DPPH-scavenging and antimicrobial activities of Asteraceae medicinal plants on uropathogenic bacteria
Authors: Phan Trinh Canh , Le Thao Thi Thanh , Hoang Ha Tran Viet , Nguyen TuAnh
Published: December 2019

Asteraceae species were widely applied in traditional medicines in Asia countries as sources of natural antioxidants and antimicrobial agents. This study aimed to evaluate DPPH-scavenging capacities and antimicrobial activities of nine Asteraceae species collected from Southern Vietnam. Antioxidant and antimicrobial activities were determined by standard protocols. Essential oils fromAgeratum conyzoides, Helianthus annuus, Artemisia vulgarisindicated significant inhibitory effects onStaphyloccocus aureusandCandidaspp.. Crude extracts and fractions fromTaraxacum officinale, Chrysanthemum morifolium, Ageratum conyzoides, Tagetes erectashowed inhibitory ability on at least one testing bacterial strains includingS. aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa. Study on clinical isolates, ethyl acetate fraction fromA. conyzoidesdisplayed the most potent effect on uropathogenicE. coliandK. pneumoniaewith MIC at 1.25-10 mg/ml and 5-12.5 mg/ml, respectively. DPPH scavenging assay indicated thatTagetes erectaextract had the lowest IC50(17.280 μg/ml) and 2.5 times higher than vitamin C (7.321 μg/ml). This study revealed thatA. conyzoideshas good potential against uropathogenicE. coliandK. pneumoniae, and could, therefore, apply to prophylactic urinary tract infection.
Characterization of neural communication dynamics in the Ventral Attention Network across distinct spatial and spatio-temporal scales
Authors: Ghosh Priyanka , Roy Dipanjan , Banerjee Arpan
Published: December 2019

The Ventral Attention Network (VAN) is involved in reorienting attention from an ongoing task when a salient (pop-out) stimulus is detected in the environment. Previous neuroimaging studies have extensively evaluated the structural and functional connectivity of the VAN. However, directed effective connectivity within the network and the neural oscillations driving it still remain elusive. Functional magnetic resonance imaging (fMRI) studies have not been able to address this issue due to lack of appropriate temporal resolution required to capture the process of reorientation. In this study, we recorded scalp electroencephalography (EEG) and behavioural data from healthy human volunteers, obtained saliency-specific spectral changes, localized the sources underlying the spectral power modulations with individual-specific structural MRI scans, reconstructed the waveforms of the sources and investigated the causal relationships between the areas of the VAN using Granger causality (GC). Using a custom-designed experiment involving visual search on static images and a dynamic motion tracking task, we investigated the neural processing of salient distractors operating at very slow and very fast time scales, respectively. Our results revealed how a task-independent but context-specific VAN encompassing the right insula, the right lateral pre-frontal cortex, the anterior and the posterior right temporo-parietal junction communicating in the alpha frequency band (8-12 Hz) supports saliency processing.
Low-dose ethanol produces mixed effects on cortico-hippocampal theta rhythms and modifies hippocampal theta frequency through multiple mechanisms
Authors: Young Calvin K. , McNaughton Neil
Published: December 2019

Ethanol is one of the most widely used drugs – with many psychoactive effects, including anxiolysis. The deleterious effects on brain function and general health of chronic and high-level ethanol use are well-studied. However, the neurophysiology of acute low dose ethanol has not been systematically investigated. Here, we examined the effects of low dose (0.25 and 0.5 g/kg) ethanol on midline (prefrontal, cingulate and retrosplenial) cortical and hippocampal theta oscillations in freely moving rats. We also tested low dose ethanol on reticular-elicited and running-elicited hippocampal theta frequency and assessed the linear relationship of theta frequency to stimulation intensity and running speed, respectively. Low dose ethanol had mixed effects on cortical theta oscillations. It most reliably reduced theta frequency, produced a weak inverted-U effect on theta power, and had no detectable effect on cortico-hippocampal theta coherence. Ethanol dose-dependently decreased the y-intercept of the speed-theta frequency function without affecting the slope, but decreased the slope of the stimulation intensity-theta frequency function without affecting the y-intercept; thus decreasing theta frequency in both cases but through different mechanisms. We conclude low dose ethanol has weak but detectable effects on cortical and hippocampal theta oscillations. These effects may underlie positive cognitive and behavioural outcomes reported in the literature using low dose ethanol. The double dissociation of slope and y-intercept specific changes relating to different methods of hippocampal theta elicitation suggests that multiple mechanisms contribute to anxiolytic effects on theta and so hippocampal function.
Temperature-dependence of metabolic rate in tropical and temperate aquatic insects: support for the Climate Variability Hypothesis in mayflies but not stoneflies
Authors: Shah Alisha A. , Woods H. Arthur , Havird Justin C. , Encalada Andrea C. , Flecker Alexander S. , Funk W. Chris , Guayasamin Juan M. , Kondratieff Boris C. , Poff N. LeRoy , Thomas Steven A. , Zamudio Kelly R. , Ghalambor Cameron K.
Published: December 2019

A fundamental gap in climate change vulnerability research is an understanding of the relative thermal sensitivity of ectotherms. Aquatic insects are vital to stream ecosystem function and biodiversity but insufficiently studied with respect to their thermal physiology. With global temperatures rising at an unprecedented rate, it is imperative that we know how aquatic insects respond to increasing temperature and whether these responses vary among taxa, latitudes, and elevations. We evaluated the thermal sensitivity of standard metabolic rate in stream-dwelling baetid mayflies and perlid stoneflies across a ~2,000 m elevation gradient in the temperate Rocky Mountains in Colorado, U.S.A., and the tropical Andes in Napo, Ecuador. We used temperature-controlled water baths and microrespirometry to estimate changes in oxygen consumption. Tropical mayflies generally exhibited greater thermal sensitivity in metabolism compared to temperate mayflies; tropical mayfly metabolic rates increased more rapidly with temperature and the insects more frequently exhibited behavioral signs of thermal stress. By contrast, temperate and tropical stoneflies did not clearly differ. Varied responses to temperature among baetid mayflies and perlid stoneflies may reflect differences in evolutionary history or ecological roles as herbivores and predators, respectively. Our results show that there is physiological variation across elevations and species and that low elevation tropical mayflies may be especially imperiled by climate warming. Given such variation among species, broad generalizations about the vulnerability of tropical ectotherms should be made more cautiously.
Coagulation factor XII, XI, and VIII activity levels and secondary events after first ischemic stroke
Authors: Rohmann Jessica L. , Huo Shufan , Sperber Pia S. , Piper Sophie K. , Rosendaal Frits R. , Heuschmann Peter U. , Endres Matthias , Liman Thomas G. , Siegerink Bob
Published: December 2019

Background and Purpose

Though risk for recurrent vascular events is high following ischemic stroke, little is known about risk factors for secondary events post-stroke. The coagulation factors XII, XI, and VII (FXII, FXI, and FVIII) have already been implicated in first thrombotic events, and our aim was to estimate their effects on vascular outcomes within 3 years after first stroke.

Methods

In the PROSpective Cohort with Incident Stroke Berlin (PROSCIS-B) study, we followed participants aged 18 and older for three years after first mild to moderate ischemic stroke event or until occurrence of recurrent stroke, myocardial infarction or all-cause mortality (combined endpoint). High coagulation factor activity levels were compared to normal and low levels, and activities were also analyzed as continuous variables. We used Cox proportional hazards models adjusted for age, sex, and cardiovascular risk factors to estimate hazard ratios (HRs) for the combined endpoint.

Results

In total, 92 events occurred in 570 included participants, resulting in an absolute rate of 6.6 events per 100 person-years. After confounding adjustment, high FVIII activity showed the strongest relationship with the combined endpoint (HR=2.05, 95%CI 1.28-3.29). High FXI activity was also associated with an increased risk (HR=1.80, 95%CI 1.09-2.98). Contrarily, high FXII activity was not associated with the combined endpoint (HR=0.86, 95%CI 0.49-1.51). Continuous analyses per standard deviation of each biomarker yielded similar results.

Conclusions

In our study of mild to moderate ischemic stroke patients, high activity levels of FXI and FVIII but not FXII were associated with worse vascular outcomes in the three-year period after first ischemic stroke. This is of special interest in light of the ongoing trials of antithrombotic treatments targeting FXI.