bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of the sonic scale in the growth of magnetic field in compressible turbulence
Authors: Fouxon Itzhak , Mond Michael
Published: February 2020

We study the growth of small fluctuations of magnetic field in supersonic turbulence, the small-scale dynamo. The growth is due to the smallest and fastest turbulent eddies above the resistive scale. We observe that for supersonic turbulence these eddies are localized below the sonic scale ls, defined as the scale where the typical velocity of the turbulent eddies equals the speed of sound, and are therefore effectively incompressible. All previous studies have ignored the existence of the sonic scale and consequently treated the entire inertial range as made up of compressible eddies. However, at large Mach numbers ls is much smaller than the integral scale of the turbulence so the fastest growing mode of the magnetic field belongs to small-scale incompressible turbulence. We determine this mode and the associated growth rate numerically with the aid of a white noise in time model of turbulence whose approximate validity for the description of the Navier–Stokes turbulence is explained. For that purpose, we introduce a new non-dimensional number Rsm that we name the magnetosonic Reynolds number that describes the division of the magnetic field amplification range between small-scale incompressible eddies and large-scale supersonic ones. We show that indeed, as Rsm grows (which means that the incompressible eddies occupy a larger portion of the magnetic field amplification range) the growth rate of the fastest growing mode increases, while the spatial distribution of the growing magnetic field shifts to smaller scales. Our result implies the existence of small-scale dynamo for compressible homogeneous turbulence.
Evidence for radio and X-ray auroral emissions from the magnetic B-type star ρ Oph A
Authors: Leto P , Trigilio C , Leone F , Pillitteri I , Buemi C S , Fossati L , Cavallaro F , Oskinova L M , Ignace R , Krtička J , Umana G , Catanzaro G , Ingallinera A , Bufano F , Agliozzo C , Phillips N M , Cerrigone L , Riggi S , Loru S , Munari M , Gangi M , Giarrusso M , Robrade J
Published: February 2020

We present new ATCA multiwavelength radio measurements (range 2.1–21.2 GHz) of the early-type magnetic star ρ Oph A, performed in 2019 March during three different observing sessions. These new ATCA observations evidence a clear rotational modulation of the stellar radio emission and the detection of coherent auroral radio emission from ρ Oph A at 2.1 GHz. We collected high-resolution optical spectra of ρ Oph A acquired by several instruments over a time span of about 10 yr. We also report new magnetic field measurements of ρ Oph A that, together with the radio light curves and the temporal variation of the equivalent width of the He i line (λ = 5015 Å), were used to constrain the rotation period and the stellar magnetic field geometry. The above results have been used to model the stellar radio emission, modelling that allowed us to constrain the physical condition of ρ Oph A’s magnetosphere. Past XMM–Newton measurements showed periodic X-ray pulses from ρ Oph A. We correlate the X-ray light curve with the magnetic field geometry of ρ Oph A. The already published XMM–Newton data have been re-analysed showing that the X-ray spectra of ρ Oph A are compatible with the presence of a non-thermal X-ray component. We discuss a scenario where the emission phenomena occurring at the extremes of the electromagnetic spectrum, radio and X-ray, are directly induced by the same plasma process. We interpret the observed X-ray and radio features of ρ Oph A as having an auroral origin.
Smoking and Quitting Behavior by Sexual Orientation: A Cross-Sectional Survey of Adults in England
Authors: Jackson Sarah E , Brown Jamie , Grabovac Igor , Cheeseman Hazel , Osborne Ciaran , Shahab Lion
Published: February 2020

Objective

To assess associations between sexual orientation and smoking and quitting behavior among adults in England.

Methods

Data were collected from 112 537 adults (≥16 years) participating in a nationally representative monthly cross-sectional survey between July 2013 and February 2019. Sexual orientation was self-reported as heterosexual, bisexual, lesbian/gay, or prefer-not-to-say. Main outcomes were smoking status, e-cigarette use, cigarettes per day, time to first cigarette, motivation to stop smoking, motives for quitting, use of cessation support, and past-year quit attempts. Associations were analyzed separately for men and women using multivariable regression models adjusted for relevant covariates.

Results

Smoking prevalence is now similar between gay (21.6%), prefer-not-to-say (20.5%) and heterosexual men (20.0%), and lesbian (18.3%) and heterosexual women (16.9%), but remains higher among bisexual men (28.2%, adjusted odds ratio [ORadj] = 1.41, 95% confidence interval [CI] = 1.11 to 1.79) and bisexual women (29.8%, ORadj = 1.64, 95% CI = 1.33 to 2.03) and lower among prefer-not-to-say women (14.5%, ORadj = 0.85, 95% CI = 0.72 to 0.99). Among smokers, bisexuals were less addicted than heterosexuals, with bisexual men smoking fewer cigarettes per day (Badj = −2.41, 95% CI = −4.06 to −0.75) and bisexual women less likely to start smoking within 30 min of waking (ORadj = 0.66, 95% CI = 0.45 to 0.95) than heterosexuals. However, motivation to stop smoking and quit attempts did not differ significantly.

Conclusions

In England, differences in smoking prevalence among people with different sexual orientations have narrowed, primarily driven by a larger decline in smoking rates among sexual minority groups than heterosexuals. Bisexual men and women remain more likely to smoke but have lower levels of addiction while being no less likely to try to quit.

Implications

This population-based study provides an up-to-date picture of smoking and quitting behavior in relation to sexual orientation among adults in England. Findings suggest that widely documented disparities in smoking prevalence have narrowed over recent years, with gay men and lesbian women no longer significantly more likely to smoke than heterosexuals, although smoking remains more common among bisexual men and women. Insights into differences in level of addiction, use of cessation support, and motives for quitting may help inform the development of targeted interventions to further reduce smoking among sexual minority groups.
Election Commission of India
Authors: Singh Ujjwal Kumar , Roy Anupama
Published: February 2020

As the constitutional body that conducts elections, the Election Commission of India (ECI) has emerged as a trusted institution within the shared space of democracy in India. This process has, however, been a fraught one because of contestation over the ECI’s constitutional responsibility and the power of Parliament to make laws to govern electoral matters. This comprehensive monograph discusses the history of the ECI through a study of the measures it has adopted to ensure certainty of procedures in order to maintain the democratic uncertainty of electoral outcome. In this context, innovations such as the Model Code of Conduct have enhanced the rule-making powers of the ECI. Going beyond the ECI’s design and performance framework, Singh and Roy argue that changes in the nature of electoral contests and domination of political regimes have made the task of preserving electoral integrity and assuring its deliberative content a challenging one.
Effects of Partisan Personalization in a News Portal Experiment
Authors: Bryanov Kirill , Watson Brian K , Pingree Raymond J , Santia Martina
Published: February 2020

What happens when news aggregators tailor their newsfeeds to include partisan news aimed at users with a known party preference? Relying on a custom-made news portal featuring real, timely articles, this study examines the influence of partisan news sources on participant headline exposure, clicks on news stories to read, and perceptions about the portal’s ability to reliably and comprehensively provide the most important news of the day. Over a period of 12 days, participants preferring either the Republican or Democratic party were randomly assigned to newsfeeds containing increased dosages of real news articles from sources supportive of the participant’s preferred party. Results demonstrate that partisan personalization can benefit a news aggregator by increasing usage and perceptions of its quality, while potentially harming society by decreasing attention to high-quality mainstream sources.
Articular manifestations in patients with inflammatory bowel disease treated with vedolizumab
Authors: Dupré Anastasia , Collins Michael , Nocturne Gaétane , Carbonnel Franck , Mariette Xavier , Seror Raphaèle
Published: February 2020

Objective

Vedolizumab (VDZ) has been incriminated in the occurrence of articular manifestations in patients with inflammatory bowel diseases (IBDs). The aim of this study was to describe musculoskeletal manifestations occurring in IBD patients treated by VDZ and to identify risk factors.

Methods

In this retrospective monocentric study, we included all consecutive patients treated by VDZ for IBD in our hospital. Incident musculoskeletal manifestations occurring during VDZ treatment were analysed and characteristics of patients with and without articular inflammatory manifestations were compared.

Results

Between 2013 and 2017, 112 patients were treated with VDZ for IBD: ulcerative colitis (n = 59), Crohn’s disease (n = 49) and undetermined colitis (n = 4). Four patients (3.6%) had a history of SpA, whereas 13 (11.6%) had a history of peripheral arthralgia. Some 102 (91.1%) patients had previously received anti-TNF. After a mean (S.d.) follow-up of 11.4 (8.6) months, 32 (28.6%) patients presented 35 musculoskeletal manifestations, of which 18 were mechanical and 17 inflammatory. Among the latter, 11 had axial or peripheral SpA, 5 had early reversible arthralgia and 1 had chondrocalcinosis (n = 1). Among the 11 SpA patients, only 3 (2.6%) had inactive IBD and may be considered as paradoxical SpA. The only factor associated with occurrence of inflammatory manifestations was history of inflammatory articular manifestation [7/16 (43.8%) vs 10/80 (12.5%), P = 0.007].

Conclusion

Musculoskeletal manifestations occurred in almost 30% of IBD patients treated with VDZ, but only half of them were inflammatory. Since most of the patients previously received anti-TNF, occurrence of inflammatory articular manifestations might rather be linked to anti-TNF discontinuation than to VDZ itself.
INDOOR RADON AND THORON IN THE VICINITY OF PROPOSED URANIUM MINING SITE: A CASE STUDY AT DASARLAPALLY VILLAGE, TELANGANA STATE, INDIA
Authors: Suman G , Reddy K Vinay Kumar , Reddy M Sreenath , Reddy Ch Gopal , Reddy P Yadagiri
Published: February 2020

Studies are being conducted for the past few decades in and around the uranium mining sites across the globe to identify environmental nuclear radiation risk to the common public. The area near Dasarlapally village was identified for uranium exploration by the AMDER, Hyderabad. The present study was carried out to measure the indoor radon and thoron activity concentrations in the dwellings of Dasarlapally village. For this purpose different types of dwellings were chosen randomly across the village. The measured annual average concentration of radon and thoron in dwellings were found to be 141 ± 42 and 139 ± 77 Bqm−3, respectively, and the calculated annual effective inhalation dose due to radon was determined to be 3.5 mSv. Seasonal variation and diurnal variation of radon and thoron activity concentration were investigated. The variation of radon and thoron activity concentration in different types of dwellings was also studied, and the variation was found to be statistically insignificant. The uncertainty propagated in the effective inhalation dose due to thoron was discussed.
Does Greater Regulatory Burden Lead to More Corruption? Evidence Using Firm-Level Survey Data for Developing Countries
Authors: Amin Mohammad , Soh Yew Chong
Published: February 2020

It is sometimes thought that regulation often creates opportunities for public officials to extract bribes. If this is true, deregulation offers a simple way of combating corruption. However, empirical evidence on the corruption and regulation nexus is limited. Further, the corruption indices used are based on experts’ opinions, which may suffer from perception bias. The present paper attempts to address these shortcomings using firm-level survey data for 131 mostly developing countries on the actual experience of the firms with bribery and regulatory burden. The study examines the level of overall corruption and petty corruption. Exploiting variation in regulatory burden, both within-country and industry-level, a large positive effect of regulatory burden on corruption is found. For the baseline results, the bribery rate is higher by about 0.03 percentage points for each percentage point increase in the regulatory burden. The finding is robust to several controls and endogeneity checks.
Antagonistic Activity of Endophytic and Rhizosphere Fungi Isolated From Sea Purslane (Sesuvium portulacastrum) Against Pythium Damping off of Cucumber
Authors: Karunasinghe Thamodini G. , Maharachchikumbura S. S. N. , Velazhahan Rethinasamy , Al-Sadi Abdullah M.
Published: February 2020

This study was conducted to investigate the antagonistic activity of endophytic and rhizosphere fungi isolated from a medicinal plant, Sesuvium portulacastrum, against Pythium aphanidermatum, the cause of damping off of cucumber. A total of 40 endophytic and 19 rhizosphere fungi were isolated from S. portulacastrum. Three endophytic isolates and two rhizosphere isolates gave >50% suppression of P. aphanidermatum in the in vitro dual-culture tests. Scanning electron microscopic studies at the inhibition zone showed hyphae wall damage and abnormal mycelial growth of the genus Pythium. Molecular analysis identified the antagonistic endophytes as Aspergillus insulicola (isolate A435), A. insulicola (A419), and Aspergillus melleus (A412) and the rhizosphere antagonists as Aspergillus terreus (A213) and Aspergillus luchuensis (A116). Except for A116, the culture filtrates of the other antagonists significantly increased the electrolyte leakage from Pythium mycelia, whereas ethyl acetate extracts of A435, A412, and A213 showed significant growth suppression. All five antagonists were able to produce varying amounts of cellulase and β-glucanase enzymes. However, A435, A412, and A213 showed significantly higher cellulase activity, whereas A435 and A116 showed the highest β-glucanase activity. Controlled glasshouse growth experiments showed that isolates A435 and A116 resulted in up to 70% control of damping off, whereas isolates A412 and A213 showed 30 to 40% damping-off control. The antagonists A435, A116, and A213 also contributed to increased cucumber shoot length as well as shoot and root dry mass. The synergetic effects of metabolites and hydrolytic enzymes could be the reason for the variation between isolates in the antagonistic activity and cucumber growth promotion. This study reports for the first time A. insulicola, A. melleus, and A. luchuensis as potential biocontrol agents against P. aphanidermatum-induced damping off of cucumber.
Classification of stress fractures of the first rib in adolescent athletes
Authors: Kawashima Kenji , Terabayashi Nobuo , Asano Hiromi , Akiyama Haruhiko
Published: February 2020

Stress fractures of the first rib occur infrequently in adolescent athletes; therefore, there have been few case reports. Initial radiographs do not always lead to the diagnosis of first rib stress fractures. This study proposed a classification system and a possible mechanism for stress fractures of the first rib using three-dimensional computed tomography (3D-CT). The data of 10 stress fractures of the first rib in adolescent athletes obtained using 3D-CT between 2007 and 2018 were reviewed. Fractures of the first rib were classified according to the location and type of the fracture line. Stress fractures of the first rib were classified into three types: type 1, center-transverse fracture; type 2, center to posterior-oblique fracture; and type 3, posterior-transverse fracture. There were three type 1 fractures, five type 2 fractures, and two type 3 fractures. The fracture lines of types 1 and 2 were on the deep groove of the subclavian artery between the anterior and middle scalene muscle attachments, which is the thinnest and weakest portion of the first rib. However, the fracture line of type 3 was across the posterior part of the first rib and located slightly away from the deep groove of the subclavian artery. A 3D-CT classification of stress fractures of the first rib in adolescent athletes was proposed. Our results suggested that there are three types of the fracture and different mechanisms that cause this type of injury. This classification system helped to implement adequate conservative therapeutic plans based on the proposed mechanism.
Outcomes in hepatocellular carcinoma patients undergoing sorafenib treatment: toxicities, cellular oxidative stress, treatment adherence, and quality of life
Authors: Baldan Ferrari Graziele , Coelho França Quintanilha Júlia , Berlofa Visacri Marília , Oliveira Vaz Camila , Cursino Maria Aparecida , Sampaio Amaral Laís , Brito Bastos  , Pereira Taynna Tatiane , de Oliveira Guarnieri João Paulo , de Godoy Torso Nadine , Passos Lima Carmen Silvia , Moriel Patricia
Published: February 2020

The study of toxicities induced by sorafenib, as well as the identification of possible mechanisms and biomarkers of these toxicities, is important to improve the treatment and quality of life of hepatocellular carcinoma (HCC) patients. This study focused on toxicities, cellular oxidative stress, adherence, and quality of life of 11 patients with HCC treated with sorafenib. Dermatotoxicity, myelotoxicity, gastro toxicity, nephrotoxicity, pain, and fatigue were investigated. For oxidative stress analysis, the peripheral blood mononuclear cells were isolated and mitochondrial superoxide anion production was measured using MitoSOX Red test. Medication adherence was evaluated based on Morisky-Green and MedTake tests. Quality of life assessment was performed using EORTC QLQ C-30 and QLQ HCC18 questionnaires. The results showed that hand-foot syndrome (45.5%), thrombocytopenia (45.5%), diarrhea (54.5%), pain (54.5%), and fatigue (36.4%) were the most prevalent toxicities. A non-statistically significant change in the levels of superoxide anion was observed after the sorafenib treatment (Wilcoxon test, P = 0.4131). Moreover, 81.8% of patients had high adherence, 100% knew the correct indication of sorafenib, 81.8% knew the correct intake and drug regimen, and 36.4% knew the correct dose of antineoplastic. There was a significant worsening in the emotional and pain domains of quality of life after the sorafenib (Wilcoxon test, P = 0.0313 and P = 0.0313, respectively). A production of superoxide anion was not correlated with toxicities (Spearman’s correlation and Mann–Whitney U tests, P > 0.05). This study suggests that oxidative stress might not be the mechanism of sorafenib toxicities.
Relationship between the Incidence of Postoperative Fistula or Dysphagia and Resection Style, Gastric Tube Formation, and Irradiation following Free Jejunal Flap Transfer
Authors: Onoda Satoshi , Kinoshita Masahito , Ariyoshi Yukino
Published: February 2020

Background:

The purpose of this study was to examine the relationship between the incidence of dysphagia or fistula formation in an anastomotic region and factors such as extent of resection, gastric tube formation, and irradiation among patients who underwent free jejunal flap transfer.

Methods:

We retrospectively examined 100 cases (88 men and 12 women; average age, 65.8 years; range, 46–88 years) in whom the evaluation of postoperative oral intake was possible after undergoing total pharyngo-laryngo-esophagectomy (TPLE) and free jejunal flap transfer. Chi-square test (with Fisher transformation, if necessary) was performed to analyze the relationship among resection styles (the resection margin extended to the oropharynx or to the cervical esophagus and gastric tube elevation), radiation therapy history, and incidence of dysphagia or fistula formation.

Results:

One hundred patients were analyzed, and complications such as postoperative fistula and dysphagia occurred in 8 (8.0%) and 20 patients (20.0%), respectively. However, no significant correlation was found between various resection factors and fistula formation or adverse events. At the reconstruction site, other complications such as postoperative lymphorrhea (7%), postoperative hematoma (4%), trachea necrosis (4%), cervical flap necrosis (1%), and thyroid necrosis (1%) occurred. These complications were managed by a cervical open wound and additional minor operation as needed.

Conclusion:

Thus, free jejunal transfer for TPLE is a good reconstruction technique with few complications and postoperative adverse events, regardless of the extent of resection and preoperative radiation therapy.
THE EFFECT OF ELECTIVE CATARACT EXTRACTION BY PHACOEMULSIFICATION IN EYES WITH VITREOMACULAR TRACTION SYNDROME
Authors: Mantopoulos Dimosthenis , Prenner Jonathan L. , Patel Vishal K. , Roth Daniel B. , Shah Sumit P. , Tsavaris Onoufrios , Fine Howard F. , Wheatley H. Matthew
Published: February 2020

Purpose:

To evaluate the effect of cataract extraction (CE) by phacoemulsification on the vitreomacular interface (VMI) of eyes with preexisting vitreomacular traction (VMT).

Methods:

Retrospective, observational case series. Patients with VMT who elected to proceed with CE, before any vitreoretinal intervention, were studied. Eyes with at least a 12-month follow-up period were included. The status of the vitreomacular adhesion at different time points was assessed using spectral-domain optical coherence tomography. The best-corrected visual acuity was recorded at different time points. Other macular and systemic comorbidities were documented.

Results:

Fifteen eyes from 15 phakic patients with symptomatic VMT were included. Six of them were male subjects. Seven patients had diabetes mellitus and two of them also had nonproliferative diabetic retinopathy. The preoperative macular comorbidities included macular hole in six eyes (Stage 1 in 3 eyes and Stage 2 or 3 in another 3 eyes), epiretinal membrane in five eyes, and cystoid macular edema in four eyes. After uncomplicated CE, the VMT was released in 5 eyes, whereas in 10 eyes, CE did not significantly change the status of the vitreomacular adhesion. Three of 3 eyes with preexisting full-thickness macular hole (Stage 2 or 3 macular hole) were found to have Stage 4 macular hole shortly after CE. In seven of seven patients with diabetes mellitus, the status of the vitreomacular interface did not change after CE. Eventually, 7 of 15 patients underwent additional pars plana vitrectomy. Compared with the baseline vision, and vision before other interventions, the visual acuity after CE improved in 5 patients, remained unchanged in 7 patients, and decreased in the 3 patients with Stage 2 or 3 macular hole. The mean preoperative and early postoperative visual acuity was 20/59 and 20/68, respectively (P > 0.05).

Conclusion:

The effect of CE in phakic eyes with known VMT varies significantly. In the current case series, every eye with VMT and Stage 2 or 3 macular hole ended up with Stage 4 macular hole, although the VMT did not change significantly in the eyes of diabetic patients. Studies with larger sample size are needed to further elucidate the impact of elective CE on VMT.
Interactive Learning Modules With Visual Feedback Improve Resident Learning in Colposcopy
Authors: Nelson Erin L. , Knudtson Jennifer F.
Published: February 2020

Objective

The Accreditation Council for Graduate Medical Education and the Council on Resident Education in Obstetrics and Gynecology have milestones and/or competencies relating to colposcopy; however, the optimal way to reach these objectives is not proscribed and left to individual programs. Here, we aim to assess resident skill, confidence levels, perceived level of knowledge, and satisfaction with colposcopic training before and after implementation of a new interactive learning module with visual feedback.

Materials and Methods

A new online educational intervention was developed by the author (E.L.N.) based on adult learning theory and introduced into our obstetrics and gynecology resident colposcopy curriculum in July 2014. We assessed performance on an objective competency examination administered at baseline and repeated after 6 months of our 24 residents.

In addition, we assessed resident confidence levels, perceived level of knowledge, and satisfaction with training before and 6 months after intervention.

Results

Scores on a national online examination improved after the intervention (p = .014). Significant improvements on the examination were seen in the sections of medical knowledge (p = .031) and management (p = .011). Residents' perceived knowledge increased significantly after the intervention (p = .030).

Conclusions

Learning outcomes improved after introduction of a novel teaching intervention.
Fingolimod for Relapsing-Remitting Multiple Sclerosis: The Experience From Saudi Arabia
Authors: Algahtani Hussein , Shirah Bader , Al Malik Yaser , Meftah Ibraheem
Published: February 2020

Background

Fingolimod (Gilenya, Novartis pharmaceuticals) is the first oral disease-modifying therapy for reducing the frequency of clinical relapses and delaying disability progression in patients with relapsing-remitting multiple sclerosis (RRMS). In this study, we aimed to evaluate the outcome of Saudi patients with active RRMS treated with fingolimod.

Methods

We conducted a retrospective multicenter observational study at the King Abdulaziz Medical City in Jeddah and Riyadh, Saudi Arabia. The inclusion criteria consisted of patients 18 years and older who were diagnosed with RRMS according to the revised McDonald criteria who are currently receiving or received fingolimod treatment in the past for a minimum of 6 months.

Results

A total of 100 patients were treated with fingolimod. The mean ± SD duration of the disease was 9.23 ± 6.63 years. The mean ± SD duration of using fingolimod was 32.00 ± 24.83 months. The mean ± SD baseline expanded disability status scale (EDSS) score was 2.95 ± 2.58. The mean ± SD EDSS score at last follow-up was 2.95 ± 2.65. The mean ± SD annualized relapse rate was significantly reduced from 1.24 ± 1.39 at baseline to 0.43 ± 1.15 at the last follow-up (P = 0.001). In addition, radiological activity was significantly improved at follow-up magnetic resonance imaging studies when compared with the baseline.

Conclusions

Our multicenter study provides further evidence for the efficacy of fingolimod in reducing clinical and radiological disease activity in patients with RRMS. The reduction in relapse rate, stabilization of the EDSS score, and improvement in magnetic resonance imaging images were similar to other observational studies conducted in different countries worldwide. Fingolimod seems to be well tolerated for our multiple sclerosis population.
Parallel cortical-brainstem pathways to attentional analgesia
Authors: Oliva Valeria , Gregory Rob , Davies Wendy-Elizabeth , Harrison Lee , Moran Rosalyn , Pickering Anthony E. , Brooks Jonathan C.W.
Published: February 2020

Pain perception is diminished when attention is diverted. Our previous human fMRI study, using a 2×2 factorial design with thermal stimuli and concurrent visual attention task, linked the brainstem triad of locus coeruleus (LC), rostroventromedial medulla (RVM) and periaqueductal grey (PAG) to attentional analgesia. This study was repeated with a larger cohort, replicating our earlier findings. Pain intensity was encoded by the RVM, whilst activity in the contralateral LC correlated with the magnitude of attentional analgesia. Psycho-Physiological Interaction analysis informed subsequent Dynamic Causal Modelling and identified two parallel paths between forebrain and the brainstem regions involved in analgesia. These cortico-brainstem connections were modulated by attentional demand: a bidirectional anterior cingulate cortex (ACC) – right-LC loop, and a top-down influence of task on ACC-PAG-RVM. Under conditions of competing attentional demands the ACC recruits discrete brainstem circuits to modulate nociceptive input.
Independent and sensitive gait parameters for objective evaluation in knee and hip osteoarthritis using wearable sensors
Authors: Boekesteijn R.J. , Smolders J.M.H. , Busch V.J.J.F. , Geurts A.C.H. , Smulders K.
Published: February 2020

Objective

To identify non-redundant gait parameters sensitive to end-stage knee and hip osteoarthritis (OA), with a specific focus on turning, dual task performance, and upper body motion in addition to straight-ahead gait.

Design

Gait was compared between individuals with unilateral, end-stage knee (n=25) or hip OA (n=26) scheduled for joint replacement, and healthy controls (n=27). For 2 minutes, subjects walked back-and-forth along a 6 meter trajectory making 180° turns, with and without a secondary cognitive task. Gait parameters were collected using 4 inertial measurement units on the feet and trunk. The dataset was reduced using factor analysis. One gait parameter from each factor was selected based on factor loading and effect size of the comparison between OA groups and healthy controls.

Results

Four independent domains of gait were obtained: speed-spatial, speed-temporal, dual task cost, and upper body motion. Turning parameters did not constitute a separate domain. From these domains, stride length (speed-spatial) and cadence (speed-temporal) had the strongest factor loadings and effect sizes for both knee and hip OA, and lumbar sagittal range of motion (upper body motion) for hip OA only.

Conclusions

Stride length, cadence, and lumbar sagittal range of motion were non-redundant and sensitive parameters, representing gait adaptations in individuals with knee or hip OA. Turning or dual task parameters had no additional value for evaluating gait in knee and hip OA. These findings hold promise for the objective evaluation of gait in the clinic. Future steps should include testing of responsiveness to interventions aiming to improve mobility.
Whole-brain estimates of directed connectivity for human connectomics
Authors: Frässle Stefan , Manjaly Zina M. , Do Cao T. , Kasper Lars , Pruessmann Klaas P. , Stephan Klaas E.
Published: February 2020

Connectomics is essential for understanding large-scale brain networks but requires that individual connection estimates are neurobiologically interpretable. In particular, a principle of brain organization is that reciprocal connections between cortical areas are functionally asymmetric. This is a challenge for fMRI-based connectomics in humans where only undirected functional connectivity estimates are routinely available. By contrast, whole-brain estimates of effective (directed) connectivity are computationally challenging, and emerging methods require empirical validation.

Here, using a motor task at 7T, we demonstrate that a novel generative model can infer known connectivity features in a whole-brain network (>200 regions, >40,000 connections) highly efficiently. Furthermore, graph-theoretical analyses of directed connectivity estimates identify functional roles of motor areas more accurately than undirected functional connectivity estimates. These results, which can be achieved in an entirely unsupervised manner, demonstrate the feasibility of inferring directed connections in whole-brain networks and open new avenues for human connectomics.
Light-inducible generation of membrane curvature in live cells with engineered BAR domain proteins
Authors: Jones Taylor , Liu Aofei , Cui Bianxiao
Published: February 2020

Nanoscale membrane curvature is now understood to play an active role in essential cellular processes such as endocytosis, exocytosis and actin dynamics. Previous studies have shown that membrane curvatures directly affect protein functions and intracellular signaling. However, few methods are able to precisely manipulate membrane curvature in live cells. Here, we report the development of a new method of generating nanoscale membrane curvature in live cells that is controllable, reversible, and capable of precise spatial and temporal manipulation. For this purpose, we make use of BAR domain proteins, a family of well-studied membrane-remodeling and membrane-sculpting proteins. Specifically, we engineered two optogenetic systems, opto-FBAR and opto-IBAR, that allow light-inducible formation of positive and negative membrane curvature respectively. Using opto-FBAR, blue light activation results in the formation of tubular membrane invaginations (positive curvature), controllable down to the subcellular level. Using opto-IBAR, blue light illumination results in the formation of membrane protrusions or filopodia (negative curvature). These systems present a novel approach for light-inducible manipulation of nanoscale membrane curvature in live cells.

Highlights

Opto-FBAR enables light-inducible positive membrane curvature formation.

Opto-IBAR enables light-inducible negative membrane curvature formation.

Light-inducible activation enables precise spatial and temporal control.

Opto-BAR systems present a new approach for studying membranes in live cells.
Matrix metalloproteinase-2 mediates ribosomal RNA transcription by cleaving nucleolar histones
Authors: Ali Mohammad A.M. , Garcia-Vilas Javier A. , Cromwell Christopher R. , Hubbard Basil P. , Hendzel Michael J. , Schulz Richard
Published: February 2020

Cell proliferation and survival require continuous ribosome biogenesis and protein synthesis. Genes encoding ribosomal RNA (rRNA) are physically located in a specialized substructure within the nucleus known as the nucleolus, which has a central role in the biogenesis of ribosomes. Matrix metalloproteinase-2 (MMP-2) was previously detected in the nucleus. However, its role there is elusive. Herein we report that MMP-2 resides within the nucleolus to regulate rRNA transcription. MMP-2 is enriched at the promoter region of rRNA gene repeats and its inhibition downregulates pre-rRNA transcription. The N-terminal tail of histone H3 is clipped by MMP-2 in the nucleolus and is associated with increased rRNA transcription. Knocking down/out MMP-2 or inhibiting its activity prevents histone H3 cleavage and reduces both rRNA transcription and cell proliferation. In addition to the known extracellular roles of MMP-2 in tumor growth, our data reveal an epigenetic mechanism whereby intranucleolar MMP-2 regulates cell proliferation through histone proteolysis and facilitation of rRNA transcription.
Biased localization of actin binding proteins by actin filament conformation
Authors: Harris Andrew R , Jreij Pamela , Belardi Brian , Bausch Andreas , Fletcher Daniel A
Published: February 2020

The assembly of actin filaments into distinct cytoskeletal structures plays a critical role in cell physiology, but how proteins localize differentially to these structures within a shared cytoplasm remains unclear. Here, we show that the actin-binding domains of accessory proteins can be sensitive to filament conformational changes. Using a combination of live cell imaging and in vitro single molecule binding measurements, we show that tandem calponin homology domains (CH1-CH2) can be mutated to preferentially bind actin networks at the front or rear of motile cells, and we demonstrate that the affinity of CH1-CH2 domain mutants varies as actin filament conformation is altered by perturbations that include stabilizing drugs, physical constraints, and other binding proteins. These findings suggest that conformational heterogeneity of actin filaments in cells could help to direct accessory binding proteins to different actin cytoskeletal structures through a biophysical feedback loop.
Allosteric regulation of lysosomal enzyme recognition by the cation-independent mannose 6-phosphate receptor
Authors: Olson Linda J. , Misra Sandeep K. , Ishihara Mayumi , Battaile Kevin P. , Grant Oliver C. , Sood Amika , Woods Robert J. , Kim Jung-Ja P. , Tiemeyer Michael , Ren Gang , Sharp Joshua S. , Dahms Nancy M.
Published: February 2020

The cation-independent mannose 6-phosphate receptor (CI-MPR), also known as the IGF2 receptor or CD222, is a multifunctional type I transmembrane glycoprotein ubiquitously expressed in most eukaryotic cell types. Through the receptor’s ability to bind a variety of unrelated extracellular and intracellular ligands, it is involved in a wide array of functions including protein trafficking, lysosomal biogenesis, internalization, regulation of cell growth, cell migration and apoptosis. CI-MPR has a large extracellular region comprised of 15 contiguous domains, four of which interact with phosphorylated glycans on lysosomal enzymes. Here we present a series of biophysical studies, along with crystal structures, providing information on how the N-terminal 5 domains of this receptor work in concert to bind and release carbohydrates. High-resolution electron microscopy as well as hydroxyl radical protein footprinting (HRPF) of this multifunctional multidomain construct demonstrates dynamic conformational changes occur as a consequence of ligand binding and different pH conditions, These data, coupled with surface plasmon resonance studies and molecular modeling, allow us to propose a bi-dentate oligosaccharide binding model, which could explain how high affinity carbohydrate binding is achieved through allosteric domain cooperativity.
Decreased Colonic Activin Receptor-Like Kinase 1 Disrupts Epithelial Barrier integrity and is associated with a poor clinical outcome in Crohn’s disease
Authors: Toyonaga Takahiko , Keith Benjamin P. , Barrow Jasmine B. , Schaner Matthew S. , Wolber Elisabeth A. , Beasley Caroline , Huling Jennifer , Wang Yuli , Allbritton Nancy L. , Chaumont Nicole , Sadiq Timothy S. , Koruda Mark J. , Rahbar Reza , Furey Terrence S. , Sethupathy Praveen , Sheikh Shehzad Z.
Published: February 2020

Objective

Intestinal epithelial cell (IEC) barrier dysfunction is critical to the development of Crohn’s disease (CD). However, the mechanism is understudied. We recently reported increased microRNA-31-5p (miR-31-5p) expression in colonic IECs of CD patients, but downstream targets are unknown.

Design

MiR-31-5p target genes were identified by integrative analysis of RNA- and small RNA-sequencing data from colonic mucosa and confirmed by qPCR in colonic IECs. Functional characterization of Activin Receptor-Like Kinase 1 (ACVRL1 or ALK1) in IECs was performedex vivousing 2 dimensional-cultured human primary colonic IECs. The impact of altered colonic ALK1 signaling in CD for the risk of surgery and endoscopic relapse was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator.

Results

ALK1was identified as a target of miR-31-5p in colonic IECs of CD patients and confirmed using a 3’-UTR reporter assay. Activation of ALK1 restricted the proliferation of colonic IECs in an EdU proliferation assay and down-regulated the expression of stemness-related genes. Activated ALK1 signaling directed the fate of colonic IEC differentiation toward colonocytes. Down-regulated ALK1 signaling was associated with increased stemness and decreased colonocyte-specific marker expression in colonic IECs of CD patients compared to healthy controls. Activation of ALK1 enhanced epithelial barrier integrity in a trans-epithelial electrical resistance permeability assay. Lower colonicALK1expression was identified as an independent risk factor for surgery and associated with a higher risk of endoscopic relapse in CD patients.

Conclusion

Decreased colonic ALK1 disrupted colonic IEC barrier integrity and associated with deteriorated clinical outcomes in CD patients.
Proteasome-Bound UCH37 Debranches Ubiquitin Chains to Promote Degradation
Authors: Deol Kirandeep K. , Crowe Sean O. , Du Jiale , Bisbee Heather , Guenette Robert G. , Strieter Eric R.
Published: February 2020

The linkage, length, and architecture of ubiquitin (Ub) chains are all important variables in providing tight control over many biological paradigms. There are clear roles for branched architectures in regulating proteasome-mediated degradation, however the proteins that selectively recognize and process these atypical chains are unknown. Here, using synthetic and enzyme-derived ubiquitin chains along with intact mass spectrometry, we report that UCH37/UCHL5, a proteasome-associated deubiquitinase, exclusively cleaves K48 branched chains. The activity and selectivity toward branched chains is markedly enhanced by the proteasomal Ub receptor RPN13/ADRM1. Using proteasome complexes reconstituted with either active or inactive UCH37 together with protein substrates modified with branched chains, we find that chain debranching promotes degradation under multi-turnover conditions. These results are further supported by proteome-wide pulse-chase experiments, which show that the loss of UCH37 activity impairs global protein turnover. Our work therefore defines UCH37 as a debranching deubiquitinase important for promoting proteasomal degradation.
Accumulative deamidation of human lens protein γS-crystallin leads to partially unfolded intermediates with enhanced aggregation propensity
Authors: Vetter Calvin J. , Thorn David C. , Wheeler Samuel G. , Mundorff Charlie , Halverson Kate , Carver John A. , David Larry L. , Lampi Kirsten J.
Published: February 2020

Age-related cataract is a major cause of blindness worldwide. Yet, the molecular mechanisms whereby large, light scattering aggregates form is poorly understood, because of the complexity of the aggregates isolated from human lenses. The predominant proteins in the lens are structural proteins called crystallins. The γS-crystallin is heavily modified in cataractous lenses by deamidation, which introduces a negative charge at labile asparagine residues. The effects of deamidation at asparagines, N14, N76, and N143, were mimicked by replacing the asparagine with aspartate using site-directed mutagenesis. The effects of these surface deamidations on the stability, unfolding, and aggregation properties of γS were determined using dynamic light scattering, chemical and thermal-denaturation, and hydrogen-deuterium exchange with mass spectrometry. We found that a small population of all the deamidation mimics aggregated directly into large light scattering bodies with a radius greater than 10 nm that contributed 14-60% of the total scattering intensity compared to 7% for WT under the same conditions. A possible mechanism was identified under partially denaturing conditions, where deamidation led to significantly more rapid unfolding and aggregation particularly for N76D compared to WT. The triple mutant was further destabilized, reflecting the enhanced aggregation properties of N14D and N143D. Thus, the effects of deamidation were both site-specific and cumulative. αA-crystallin was ineffective at acting as a chaperone to prevent the aggregation of destabilized, deamidated γS. It is concluded that surface deamidations, while causing minimal structural disruption individually, progressively destabilize crystallin proteins, leading to their unfolding and precipitation in aged and cataractous lenses.
Visualizing ultrastructural details of placental tissue with super-resolution structured illumination microscopy
Authors: Villegas-Hernández Luis E. , Nystad Mona , Ströhl Florian , Basnet Purusotam , Acharya Ganesh , Ahluwalia Balpreet S.
Published: February 2020

Super-resolution fluorescence microscopy is a widely employed technique in cell biology research, yet remains relatively unexplored in the field of histo-pathology. Here, we describe the sample preparation steps and acquisition parameters necessary to obtain fluorescent multicolor super-resolution structured illumination microscopy (SIM) images of both formalin-fixed paraffin-embedded and cryo-preserved placental tissue sections. We compare super-resolved images of chorionic villi against diffraction-limited deconvolution microscopy and demonstrate the significant contrast and resolution enhancement attainable with SIM. We show that SIM resolves ultrastructural details such as the syncytiotrophoblast’s microvilli brush border, which up until now has been only resolvable by electron microscopy.
WeChat, a Chinese social media, may early detect the SARS-CoV-2 outbreak in 2019
Authors: Wang Wenjun , Wang Yikai , Zhang Xin , Li Yaping , Jia Xiaoli , Dang Shuangsuo
Published: February 2020

We plotted daily data on the frequencies of keywords related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from WeChat, a Chinese social media. Using “Feidian”, Chinese abbreviation for SARS, may detect the SARS-CoV-2 outbreak in 2019 two weeks earlier. WeChat offered a new approach to early detect disease outbreaks.
Multi-proxy evidence for the impact of the Storegga Slide Tsunami on the early Holocene landscapes of the southern North Sea
Authors: Gaffney Vincent , Fitch Simon , Bates Martin , Ware Roselyn L. , Kinnaird Tim , Gearey Benjamin , Hill Tom , Telford Richard , Batt Cathy , Stern Ben , Whittaker John , Davies Sarah , Sharada Mohammed Ben , Everett Rosie , Cribdon Rebecca , Kistler Logan , Harris Sam , Kearney Kevin , Walker James , Muru Merle , Hamilton Derek , Law Matthew , Bates Richard , Allaby Robin G.
Published: February 2020

Doggerland was a land mass occupying an area currently covered by the North Sea until marine inundation took place during the mid-Holocene, ultimately separating the British land mass from the rest of Europe. The Storegga Slide, which triggered a tsunami reflected in sediment deposits in the Northern North Sea, North East coastlines of the British Isles and across the North Atlantic, was a major event during this transgressive phase. The spatial extent of the Storegga tsunami however remains unconfirmed because to date no direct evidence for the event has been recovered from the southern North Sea. We present evidence that Storegga associated deposits occur in the southern North Sea. Palaeo-river systems have been identified using seismic survey in the southwestern North Sea and sedimentary cores extracted to track the Mid Holocene inundation. At the head of one palaeo-river system near the Outer Dowsing Deep, theSouthern River, we observed an abrupt and catastrophic inundation stratum. Based on lithostratigraphic, macro and microfossils and sedimentary ancient DNA (sedaDNA) evidence, supported by optical stimulation luminescence (OSL) and radiocarbon dating, we conclude these deposits were a result of the Storegga event. Seismic identification of this stratum to adjacent cores indicated diminished traces of the tsunami, largely removed by subsequent erosional processes. Our results demonstrate the catastrophic impact of Storegga within this area of the Southern North Sea, but indicate that these effects were temporary and likely localized and mitigated by the dense woodland and topography of the area. We conclude clear physical remnants of the wave are likely to be restricted to inland basins and incised river valley systems.