bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency-driven bulk-to-surface transition of conductivity in ZnO nanowires
Authors: Javadi Mohammad , Abdi Yaser
Published: August 2018

The frequency of an applied AC voltage dramatically affects the nature of conductivity in zinc oxide nanowires. The nanowires exhibit a continuous transition from positive to negative photoconductivity as a function of the driving frequency with the characteristic transition frequency observed at 48.9 kHz. In addition, ZnO nanowires display a frequency-driven metal-insulator transition at room temperature, which appears almost at the same critical frequency. The responsible mechanism for both transitions is attributed to the switching of conductivity from bulk to surface conduction. A theory is presented describing the experimental observations. The frequency-driven bulk-to-surface transition of conductivity is expected to be a generic character for a broad range of semiconductor nanostructures with the large surface-to-volume ratio.
Fabrication of novel biological substrate based on photolithographic process for surface enhanced Raman spectroscopy
Authors: Zou Qiang , Mo Shentong , Pei Xiaochang , Wang Yanan , Xue Tao , Mayilamu Musideke , Qin Guoxuan
Published: August 2018

In this paper, a novel surface-enhanced Raman scattering (SERS) substrate based on Integrated Circuit (IC) process was designed, using photolithography, etching and other processes on the silicon wafer processing. Its surface morphology and Raman activity were characterized and tested. The relationship between the substrate’s photolithographic pattern and its Raman activity, stability and reproducibility has been analyzed and verified, and some suggestions for improvement of processing steps were given. This substrate can be used for the detection of biological proteins and provides a powerful research tool for life science and analytical chemistry research.
Connectedness percolation of hard convex polygonal rods and platelets
Authors: Drwenski Tara , van Roij René , van der Schoot Paul
Published: August 2018

The properties of polymer composites with nanofiller particles change drastically above a critical filler density known as the percolation threshold. Real nanofillers, such as graphene flakes and cellulose nanocrystals, are not idealized disks and rods but are often modeled as such. Here we investigate the effect of the shape of the particle cross section on the geometric percolation threshold. Using connectedness percolation theory and the second-virial approximation, we analytically calculate the percolation threshold of hard convex particles in terms of three single-particle measures. We apply this method to polygonal rods and platelets and find that the universal scaling of the percolation threshold is lowered by decreasing the number of sides of the particle cross section. This is caused by the increase of the surface area to volume ratio with decreasing number of sides.
Dynamic nuclear polarization of carbonyl and methyl 13C spins of acetate using 4-oxo-TEMPO free radical
Authors: Parish Christopher , Niedbalski Peter , Kiswandhi Andhika , Lumata Lloyd
Published: August 2018

Hyperpolarization of 13C-enriched biomolecules via dissolution dynamic nuclear polarization (DNP) has enabled real-time metabolic imaging of a variety of diseases with superb specificity and sensitivity. The source of the unprecedented liquid-state nuclear magnetic resonance spectroscopic or imaging signal enhancements of >10 000-fold is the microwave-driven DNP process that occurs at a relatively high magnetic field and cryogenic temperature. Herein, we have methodically investigated the relative efficiencies of 13C DNP of single or double 13C-labeled sodium acetate with or without 2H-enrichment of the methyl group and using a 4-oxo-TEMPO free radical as the polarizing agent at 3.35 T and 1.4 K. The main finding of this work is that not all 13C spins in acetate are polarized with equal DNP efficiency using this relatively wide electron spin resonance linewidth free radical. In fact, the carbonyl 13C spins have about twice the solid-state 13C polarization level of methyl 13C spins. Deuteration of the methyl group provides a DNP signal improvement of methyl 13C spins on a par with that of carbonyl 13C spins. On the other hand, both the double 13C-labeled [1,2-13C2] acetate and [1,2-13C2, 2H3] acetate have a relative solid-state 13C polarization at the level of [2-13C] acetate. Meanwhile, the solid-state 13C T1 relaxation times at 3.35 T and 1.4 K were essentially the same for all six isotopomers of 13C acetate. These results suggest that the intramolecular environment of 13C spins plays a prominent role in determining the 13C DNP efficiency, while the solid phase 13C T1 relaxation of these samples is dominated by the paramagnetic effect due to the relatively high concentration of free radicals.
Controlling the electrical conductivity of ternary wurtzite-type and metastable β-AgGaO2 by impurity doping
Authors: Nagatani Hiraku , Suzuki Issei , Takemura Sayuri , Ohsawa Takeo , Ohashi Naoki , Fujimoto Shinji , Omata Takahisa
Published: August 2018

We studied electron carrier doping into the ternary wurtzite β-AgGaO2 by impurity doping. Ti-doped β-NaGaO2, i.e., β-Na(Ga1−xTix)O2, was prepared by a conventional high-temperature solid-state reaction; then, we performed ion-exchange of Na+ ions with Ag+ ions into the Ti-doped β-NaGaO2 in a molten nitrate salt to produce Ti-doped β-AgGaO2: β-Ag(Ga1−xTix)O2. A single ternary wurtzite phase was obtained at compositions of 0≤x≤0.05. Ti-doped β-AgGaO2 showed an electrical conductivity at room temperature that was one to three orders of magnitude higher than that of undoped β-AgGaO2. The Ti-doped β-AgGaO2 samples showed an electron carrier density in the range of 1018−1019 cm−3, based on the free-carrier absorption shown in their optical absorption spectra. These results show that carrier injection by impurity doping into metastable β-CuMIIIO2 and β-AgMIIIO2 is possible by using an impurity-doped β-NaGaO2 precursor. This result encourages the development of optoelectronic devices based on the narrow-band-gap oxide semiconductors of β-CuMIIIO2 and β-AgMIIIO2.
Least energy solutions for a class of fractional Schrödinger-Poisson systems
Authors: Shen Liejun , Yao Xiaohua
Published: August 2018

In this paper, the existence of a nontrivial least energy solution is considered for the nonlinear fractional Schrödinger-Poisson systems (−Δ)su + V(x)u + ϕu = |u|p−1u and (−Δ)tϕ = u2 in R3, where (−Δ)α is the fractional Laplacian for α = s, t ∈ (0, 1) with s < t and 2s + 2t > 3. Under some appropriate assumptions on the non-constant potential V(x), we prove the existence of a nontrivial least energy solution when 2<p<2s*−1=(3+2s)/(3−2s) by using some new analytical skills and the Nehari-Pohožaev type manifold.
Relationship between latent and rebound viruses in a clinical trial of anti–HIV-1 antibody 3BNC117
Authors: Cohen Yehuda Z. , Lorenzi Julio C.C. , Krassnig Lisa , Barton John P. , Burke Leah , Pai Joy , Lu Ching-Lan , Mendoza Pilar , Oliveira Thiago Y. , Sleckman Christopher , Millard Katrina , Butler Allison L. , Dizon Juan P. , Belblidia Shiraz A. , Witmer-Pack Maggi , Shimeliovich Irina , Gulick Roy M. , Seaman Michael S. , Jankovic Mila , Caskey Marina , Nussenzweig Michel C.
Published: August 2018

A clinical trial was performed to evaluate 3BNC117, a potent anti–HIV-1 antibody, in infected individuals during suppressive antiretroviral therapy and subsequent analytical treatment interruption (ATI). The circulating reservoir was evaluated by quantitative and qualitative viral outgrowth assay (Q2VOA) at entry and after 6 mo. There were no significant quantitative changes in the size of the reservoir before ATI, and the composition of circulating reservoir clones varied in a manner that did not correlate with 3BNC117 sensitivity. 3BNC117 binding site amino acid variants found in rebound viruses preexisted in the latent reservoir. However, only 3 of 217 rebound viruses were identical to 868 latent viruses isolated by Q2VOA and near full-length sequencing. Instead, 63% of the rebound viruses appeared to be recombinants, even in individuals with 3BNC117-resistant reservoir viruses. In conclusion, viruses emerging during ATI in individuals treated with 3BNC117 are not the dominant species found in the circulating latent reservoir, but frequently appear to represent recombinants of latent viruses.
Rapid constriction of the selectivity filter underlies C-type inactivation in the KcsA potassium channel
Authors: Li Jing , Ostmeyer Jared , Cuello Luis G. , Perozo Eduardo , Roux Benoît
Published: August 2018

C-type inactivation is a time-dependent process observed in many K+ channels whereby prolonged activation by an external stimulus leads to a reduction in ionic conduction. While C-type inactivation is thought to be a result of a constriction of the selectivity filter, the local dynamics of the process remain elusive. Here, we use molecular dynamics (MD) simulations of the KcsA channel to elucidate the nature of kinetically delayed activation/inactivation gating coupling. Microsecond-scale MD simulations based on the truncated form of the KcsA channel (C-terminal domain deleted) provide a first glimpse of the onset of C-type inactivation. We observe over multiple trajectories that the selectivity filter consistently undergoes a spontaneous and rapid (within 1–2 µs) transition to a constricted conformation when the intracellular activation gate is fully open, but remains in the conductive conformation when the activation gate is closed or partially open. Multidimensional umbrella sampling potential of mean force calculations and nonequilibrium voltage-driven simulations further confirm these observations. Electrophysiological measurements show that the truncated form of the KcsA channel inactivates faster and greater than full-length KcsA, which is consistent with truncated KcsA opening to a greater degree because of the absence of the C-terminal domain restraint. Together, these results imply that the observed kinetics underlying activation/inactivation gating reflect a rapid conductive-to-constricted transition of the selectivity filter that is allosterically controlled by the slow opening of the intracellular gate.
Light echoes from the plateau in Eta Carinae’s Great Eruption reveal a two-stage shock-powered event
Authors: Smith Nathan , Andrews Jennifer E , Rest Armin , Bianco Federica B , Prieto Jose L , Matheson Tom , James David J , Smith R Chris , Strampelli Giovanni Maria , Zenteno A
Published: August 2018

We present multi-epoch photometry and spectroscopy of a light echo from η Carinae’s 19th century Great Eruption. This echo's light curve shows a steady decline over a decade, sampling the 1850s plateau of the eruption. Spectra show the bulk outflow speed increasing from ∼150 km s−1 at early times, up to ∼600 km s−1 in the plateau. Later phases also develop remarkably broad emission wings indicating mass accelerated to more than  10 000 km s−1. Together with other clues, this provides direct evidence for an explosive ejection. This is accompanied by a transition from a narrow absorption line spectrum to emission lines, often with broad or asymmetric P Cygni profiles. These changes imply that the pre-1845 luminosity spikes are distinct from the 1850s plateau. The key reason for this change may be that shock interaction with circumstellar material (CSM) dominates the plateau. The spectral evolution of η Car closely resembles that of the decade-long eruption of UGC 2773-OT, which had clear signatures of shock interaction. We propose a two-stage scenario for η Car’s eruption: (1) a slow outflow in the decades before the eruption, probably driven by binary interaction that produced a dense equatorial outflow, followed by (2) explosive energy injection that drove CSM interaction, powering the plateau and sweeping slower CSM into a fast shell that became the Homunculus. We discuss how this sequence could arise from a stellar merger in a triple system, leaving behind the eccentric binary seen today. This gives a self-consistent scenario that may explain interacting transients across a wide range of initial mass.
Early versus Delayed Extracranial-Intracranial Bypass Surgery in Symptomatic Atherosclerotic Occlusion
Authors: Rice Cory J , Cho Sung-Min , Taqui Ather , Moore Nina Z , Witek Alex M , Bain Mark D , Uchino Ken
Published: August 2018

Background

Clinical trials of extracranial-intracranial (EC-IC) bypass surgery studied patients in subacute and chronic stage after ischemic event.

OBJECTIVE

To investigate the short-term outcomes of EC-IC bypass in progressive acute ischemic stroke or recent transient ischemic attacks.

Methods

The study was a retrospective review at a single tertiary referral center from 2008 to 2015. Inclusion criteria consisted of EC-IC bypass within 1 yr of last ischemic symptoms ipsilateral to atherosclerotic occlusion of internal carotid or middle cerebral artery. Early bypass group who underwent surgery within 7 d of last ischemic symptoms were compared to late bypass group who underwent surgery >7 d from last ischemic symptom. The primary endpoint was perioperative ischemic or hemorrhagic stroke or intracranial hemorrhage within 7 d of surgery.

Results

Of 126 patients who underwent EC-IC bypass during the period, 81 patients met inclusion criteria, 69 (85%) persons had carotid artery occlusion, 7 (9%) had proximal MCA occlusion, and 5 (6%) had both. Early surgery had a 31% (9/29) perioperative stroke rate compared to 11.5% (6/52) of patients undergoing late bypass (P = .04). Of patients with acute stroke within 7 d of surgery, 41% (7/17) had perioperative stroke within 7 d (P = .07). Six of nine patients (67%) with blood pressure dependent fluctuation of neurologic symptoms had perioperative stroke (P = .049).

Conclusion

EC-IC bypass in setting of acute symptomatic stroke within 1 wk may confer higher risk of perioperative stroke. Patients undergoing expedited or urgent bypass for unstable or fluctuating stroke symptoms might be at highest risk for perioperative stroke.
Clinically Relevant Effect of UGT1A4*3 on Lamotrigine Serum Concentration Is Restricted to Postmenopausal Women—A Study Matching Therapeutic Drug Monitoring and Genotype Data From 534 Patients
Authors: Smith Robert L. , Haslemo Tore , Chan Hilde F. , Refsum Helge , Molden Espen
Published: August 2018

Background:

Previous studies have reported inconsistent findings regarding the impact of the UGT1A4*3 variant allele on lamotrigine (LTG) exposure. As no studies have controlled for nongenetic factors, the aim of this study was to compare serum concentrations of LTG in carriers versus noncarriers of UGT1A4*3 adjusting for differences in age, sex, and valproic acid (VPA) comedication.

Methods:

Matched data on serum concentration of LTG and UGT1A4 genotype patients with known information about VPA comedication were included retrospectively from a therapeutic drug monitoring service. Linear mixed-model analysis was used to evaluate the impact of the UGT1A4*3 variant on dose-adjusted serum concentrations (C/D ratio) of LTG. Subanalyses were performed to assess the impact of UGT1A4*3 in relation to age, sex, and VPA comedication.

Results:

In total, 534 patients (1735 LTG serum concentrations) were included. In the study population, UGT1A4*3 carriers (n = 87; 16.3%) were estimated to have a 13% lower LTG C/D ratio compared with noncarriers (P = 0.01). Subanalyses showed that the quantitative impact of UGT1A4*3 was greatest in postmenopausal women (>50 years) without VPA comedication. In these patients (n = 99), UGT1A4*3 carriers displayed a 40% lower LTG C/D ratio than noncarriers (P = 0.001). The UGT1A4*3 variant had no significant effect on LTG C/D ratio in the other subpopulations (P > 0.1). Regardless of patient subgroup, the concomitant use of VPA was the strongest determinant of LTG exposure by increasing the C/D ratio 2.5-fold (P < 0.001).

Conclusions:

This study shows that UGT1A4*3 generally has a modest impact on LTG exposure, but it could lead to clinically relevant lowering in LTG serum concentration among postmenopausal women. The clinical impact of UGT1A4*3 in these patients needs to be assessed in relation to comedication with VPA, which is associated with a substantial increase in serum concentration of LTG.
Patterns of pain-related activity: replicability, treatment-related changes, and relationship to functioning
Authors: Cane Douglas , Nielson Warren R. , Mazmanian Dwight
Published: August 2018

Changes in activity patterns frequently accompany the experience of chronic pain. Two activity patterns, avoidance and overdoing, are hypothesized to contribute to the development of ongoing pain and pain-related disability, while activity pacing is frequently introduced to enhance pain management and functioning. Two studies were conducted to assess whether reliable subgroups with differing activity patterns could be identified in different pain populations and to evaluate changes in these subgroups after a group format, pain management program. In study 1, individuals with ongoing pain being assessed for treatment at 2 different tertiary care pain centres completed a measure of pain-related activity. Separate cluster analyses of these samples produced highly similar cluster solutions. For each sample, a 2-cluster solution was obtained with clusters corresponding to the activity patterns described by the avoidance–endurance model of pain. In study 2, a subset of individuals completing a 12-session, group format, pain management program completed measures of pain-related activity, pain intensity, and physical and psychological functioning at the beginning and end of the program. At the conclusion of the program, 4 clusters of pain-related activity were identified. Individuals who used high levels of activity pacing and low levels of avoidance consistently reported significantly better functioning relative to all other individuals. Observed changes in activity patterns from pre-treatment to post-treatment suggested that decreasing the association between activity pacing and avoidance was associated with better functioning. These results have implications for both the assessment of activity pacing and for its use as an intervention in the management of ongoing pain.
Nonalcoholic steatohepatitis, obesity, and cardiac dysfunction
Authors: Mathews Sherin E. , Kumar Rekha B. , Shukla Alpana P.
Published: August 2018

Purpose of review

Obesity and nonalcoholic steatohepatitis (NASH) are epidemiologically and pathophysiologically linked disorders. Here, we summarize the effect of obesity on NASH and how it has a cascading effect on cardiovascular dysfunction. We also review the current and emerging treatment options for NASH.

Recent findings

The link between NASH and cardiac dysfunction has been further delineated in recent studies demonstrating endothelial dysfunction, diastolic dysfunction, and increased coronary artery calcification in patients with known NASH. Standard treatment of obesity with lifestyle interventions including diet, exercise, and behavioral modification has been shown to improve NASH as well as reduce cardiovascular dysfunction. In addition to FDA-approved drugs like vitamin E and pioglitazone, several agents including NGM282, obeticholic acid, elafibranor, and liraglutide are currently being investigated for their therapeutic potential in NASH. Recent studies show that bariatric surgery results in significant improvement or resolution of NASH.

Obesity is a major factor in the development of nonalcoholic fatty liver disease (NAFLD) and its progression to steatohepatitis. Patients with NAFLD have a significant increase in cardiovascular disease risk. For biopsy-proven NASH, vitamin E and pioglitazone are the recommended medical treatments in addition to lifestyle modification.
Engaging Stakeholders to Develop a Patient-centered Research Agenda
Authors: Haynes Sarah C. , Rudov Lindsey , Nauman Elizabeth , Hendryx Lindsay , Angove Rebekah S.M. , Carton Thomas
Published: August 2018

Background:

Patient-centered research requires a focus on the needs and priorities of patients. Because patient engagement can result in the discovery of important topics not currently prioritized by research programs, topic generation, and prioritization activities conducted with patients, caregivers, and other stakeholders are essential. To develop patient-centered research agendas for obesity and diabetes, the Research Action for Health Network conducted topic generation and prioritization activities with multistakeholder research advisory groups.

Objectives:

The purpose of this case study was to demonstrate how methods for engaging patients in topic generation and prioritization can be implemented in practice for the development of a patient-centered research agenda.

Research Design:

Four multistakeholder groups comprising patients, clinicians, and researchers met 4–5 times between November 2014 and July 2015 to generate and prioritize topics for obesity and diabetes research. Topics were prioritized using an iterative engagement process, in which themes were identified and resulting topics were refined and ranked over multiple meetings.

Participants:

Sixty-four patients, clinicians, and researchers participated in 2 obesity and 2 diabetes advisory groups. The majority of participants (64.0%) were patients, followed by clinicians (23.4%), researchers (9.4%), and parents of children with diabetes (3.1%).

Results:

Ten and 12 priority topics were identified for obesity and diabetes, respectively. The resulting research agendas were disseminated to patients, researchers, and clinicians.

Conclusions:

Patient engagement has the potential to enrich our understanding of patient priorities for research. The results from this process suggest that convening in-person multistakeholder groups can be an effective way to generate research topics that reflect patients’ priorities. Engagement strategies should be focused not only on the development of patient-centered research topics but also on the implementation of these topics into research studies.
Patient Governance in a Patient-Powered Research Network for Adult Rheumatologic Conditions
Authors: Nowell W. Benjamin , Curtis Jeffrey R. , Crow-Hercher Rachelle
Published: August 2018

Background:

Patient-Powered Research Networks (PPRNs) are a unique type of patient-powered patient registry for patient-centered outcomes research requiring that stakeholder engagement play a key role in governance (eg, research guidance and decision making). The purpose of this report is to describe the governance structure of a newly formed PPRN and the activities undertaken prelaunch and postlaunch to evaluate and improve the engagement of patient stakeholders in governance.

Methods:

During the 18-month start-up period of ArthritisPower, a PPRN for adult rheumatologic conditions, 12 members of the patient body of the PPRN governance completed a 12-item preassessment and postassessment based on the Patient-Centered Outcomes Research Institute (PCORI) Engagement Rubric. The assessment was intended to measure Patient Governor (PG) perceptions of their engagement in governance within the first 3 months of their involvement at an in-person orientation. Six months later, the PG Chair initiated a mid-year evaluation with the same group to identify areas for improvement. Semistructured phone interviews were conducted with 11 PGs who were asked to rate and explain their perceptions about their participation in PPRN governance, the progress of the PPRN toward conducting research, the support they receive from staff, and the support they receive from other PGs. Results were compiled and interpreted by the Chair with help from the coprincipal investigator.

Results:

Preassessment/postassessments indicated that PGs understood their governance role and decision-making authority after in-person orientation and felt that major PPRN decisions were being made with their input. Feedback and scores from the PG-led mid-year evaluation coalesced around 3 themes: a preference for receiving news and updates via email to allow more discussion and decision making during conference calls, a desire for guidance about how best to help advance the PPRN toward the conduct of research, and a need to communicate with each other as a group outside of monthly conference calls. Suggested activities to support patient engagement in PPRN governance include communicating clear expectations, providing well-prepared tools for engagement, and conducting regular assessments.

Conclusions:

Members of an online patient community are willing to share their expertise to participate in and shape research governance and bring both their professional and lived health experience to the development and improvement of PPRN governance structure. A patient-initiated and patient-led evaluation of governance communication procedures within the PPRN provided more specific recommendations for improvement than did an investigator-led preevaluation/postevaluation based on the PCORI Engagement Rubric.
Additive Interactions Between Gender and Bullying Victimization on Depressive Symptoms and Suicidality
Authors: Pontes Nancy M.H. , Ayres Cynthia G. , Pontes Manuel C.F.
Published: August 2018

Background

Bullying victimization is common among adolescents and increases the likelihood of depressive symptoms and suicidality. Two previous meta-analyses have shown that these relationships do not significantly vary by gender.

Objectives

This research investigated whether there are significant positive additive interactions between bullying victimization and female gender on depressive symptoms, suicidal ideation, suicide attempts, and suicide attempts that required treatment.

Methods

For this research, analyses of pooled data from the 2011, 2013, and 2015 Youth Risk Behavior Survey (N = 44,632) were performed to estimate measures of additive interaction, as well as measures of multiplicative interaction in order to examine whether the relationship between bullying victimization and depressive symptoms or suicidality significantly varied by gender.

Results

Measures of additive interaction show that the magnitude of the relationship between bullying victimization and depressive symptoms or suicidality is significantly greater among female than male individuals. In contrast, measures of multiplicative interaction indicate that the magnitude of the relationship between bullying and depressive symptoms or suicidality is not significantly greater among female than male individuals.

Discussion

Measures of additive interaction are relevant for nursing and population health research. Future research should further explore how and why bullying victimization appears to more profoundly affect female individuals more than male individuals and how to mitigate it.
Knowledge of Pelvic Floor Disorders in Obstetrics
Authors: Mckay Elishia R. , Lundsberg Lisbet S. , Miller Devin T. , Draper Ashley , Chao Jamie , Yeh Judy , Rangi Sabrina , Torres Priscilla , Stoltzman Michelle , Guess Marsha K.
Published: August 2018

Objectives

The aim of this study was to investigate knowledge and demographic factors associated with a lack of knowledge proficiency about urinary incontinence (UI) and pelvic organ prolapse (POP) among pregnant and postpartum women.

Methods

This was a cross-sectional survey of women receiving antepartum and postpartum care at 9 Connecticut sites. Knowledge was assessed using the validated Prolapse and Incontinence Knowledge Questionnaire. Lack of knowledge proficiency was defined as less than 80% and less than 50% correct responses on the Prolapse and Incontinence Knowledge Questionnaire UI and POP subscales. Logistic regression was used to evaluate unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs). P < 0.05 was considered statistically significant.

Results

Surveys from 399 diverse pregnant and postpartum women were analyzed. Three quarters showed a lack of knowledge proficiency about UI and POP (74.2%, 70.6%). After adjustment, increased odds of lacking UI knowledge proficiency were associated with primiparity versus nulliparity (OR, 4.73; 95% CI, 2.24–9.98), Hispanic versus white race (OR, 2.72; 95% CI, 1.18–6.01), and having a high school diploma/General Education Development/less (OR, 3.17; 95% CI, 1.34–7.48) or some college (OR, 2.55; 95% CI, 1.08–6.01) versus bachelor’s degree; greater lack of POP knowledge proficiency was associated with having a high school diploma/General Education Development versus bachelor’s degree (OR, 2.11; 95% CI, 1.05–4.26) and never seeing a urologist/urogynecologist versus those who had (OR, 0.30; 95% CI, 0.12–0.77). Women working in a medical field versus those who did not demonstrated decreased odds of lacking UI and POP knowledge proficiency (ORs, 0.26 [95% CI, 0.13–0.52] and 0.38 [95% CI, 0.21–0.70]).

Conclusions

Pregnant and postpartum women lack knowledge about UI and POP. Preconceptional counseling provides an opportunity for educational intervention.
Horizontal gene flow into Geobacillus is constrained by the chromosomal organization of growth and sporulation
Authors: Esin Alexander , Ellis Tom , Warnecke Tobias
Published: August 2018

Horizontal gene transfer (HGT) in bacteria occurs in the context of adaptive genome architecture. As a consequence, some chromosomal neighbourhoods are likely more permissive to HGT than others. Here, we investigate the chromosomal topology of horizontal gene flow into a clade of Bacillaceae that includes Geobacillusspp. Reconstructing HGT patterns using a phylogenetic approach coupled to model-based reconciliation, we discover three large contiguous chromosomal zones of HGT enrichment. These zones encompass and connect classically defined genomic islands. Analyzing topological and strand biases of recent and older transfer events, we show that restrictions on entry are rapidly enforced by selection and that restrictive and permissive zones have existed in their current locations for long periods of evolution. The largest zone, characterized by a high influx of metabolic genes, is centred on the terminus. The other two zones flank a narrow non-permissive zone around the origin of replication and extend to delimit the first third of the chromosome – the part of the chromosome that is confined to the forespore during early spore formation. Horizontal transfers into this area are biased towards functions classically controlled by the forespore-specific sigma factor σF: signal transduction, transcription, and particularly membrane biogenesis. Similar enrichment patterns are present in spore-forming but absent in non-spore-forming Bacilli. Our results suggest that the topology of HGT in Geobacillus, and Bacilli more generally, reflects constraints imposed by chromosomal organization for fast and sporulation, as asymmetric chromosomal entrapment in the forespore during early spore formation restricts where HGT-driven innovation in sporulation can occur.
Modified TCA/acetone precipitation of plant proteins for proteomic analysis
Authors: Niu Liangjie , Zhang Hang , Wu Zhaokun , Wang Yibo , Liu Hui , Wu Xiaolin , Wang Wei
Published: August 2018

Protein extracts obtained from cells or tissues often require removal of interfering substances for the preparation of high-quality protein samples in proteomic analysis. A number of protein extraction methods have been applied to various biological samples. TCA/acetone precipitation and phenol extraction, a common method of protein extraction, is thought to minimize protein degradation and activity of proteases as well as reduce contaminants like salts and polyphenols. However, the TCA/acetone precipitation method relies on the complete pulverization and repeated rinsing of tissue powder to remove the interfering substances, which is laborious and time-consuming. In addition, by prolonged incubation in TCA/acetone, the precipitated proteins are more difficult to re-dissolve. We have described a modified method of TCA/acetone precipitation of plant proteins for proteomic analysis. Proteins of cells or tissues were extracted using SDS-containing buffer, precipitated with equal volume of 20% TCA/acetone, and washed with acetone. Compared to classical TCA/acetone precipitation and simple acetone precipitation, this protocol generates comparable yields, spot numbers, and proteome profiling, but takes less time (ca. 45 min), thus avoiding excess protein modification and degradation after extended-period incubation in TCA/acetone or acetone. The modified TCA/acetone precipitation method is simple, fast, and suitable for proteomic analysis of various plant tissues in proteomic analysis.
Age and genetic background determine hybrid male sterility in house mice
Authors: Widmayer Samuel J. , Aylor David L.
Published: August 2018

Hybrid male sterility (HMS) is a unique type of reproductive isolation commonly observed between house mouse (Mus musculus) subspecies in the wild and in laboratory crosses. We identified hybrids that display three distinct trajectories of fertility despite having identical genotypes at the major HMS gene Prdm9 and the X Chromosome. In each case, we crossed female PWK/PhJ mice representative of the M.m.musculus subspecies to males from classical inbred strains representative of M.m.domesticus: 129S1/SvImJ, A/J, C57BL/6J, and DBA/2J. PWK129S1 males are always sterile, while PWKDBA2 males escape HMS. In addition, we observe age-dependent sterility in PWKB6 and PWKAJ males. These males are fertile between 15 and 35 weeks with moderate penetrance. These results point to multiple segregating HMS modifier alleles, some of which have an age-dependent mode of action. Age-dependent mechanisms could have broad implications for the maintenance of reproductive barriers in nature.

Author Summary

Two subspecies of house mice show partial reproductive barriers in nature, and may be in the process of speciation. We used mice derived from each subspecies to replicate hybrid male sterility (HMS) in laboratory mice. Two major genetic factors are well established as playing a role in mouse HMS, but the number of additional factors and their mechanisms are unknown. We characterized reproductive trait variation in a set of hybrid male mice that were specifically designed to eliminate the effects of known genetic factors. We discovered that age played an important role in fertility of some hybrids. These hybrid males showed a delayed onset of fertility, then became fertile for only a few weeks. Across all hybrids males in our study, we observed three distinct trajectories of fertility: complete fertility, complete sterility, and age-dependent fertility. These results point to two or more critical HMS variants with large enough effects to completely restore fertility. This study advances our understanding of the genetic architecture and biological mechanisms of reproductive isolation in mice.
Inter-species differences in response to hypoxia in iPSC-derived cardiomyocytes from humans and chimpanzees
Authors: Ward Michelle C. , Gilad Yoav
Published: August 2018

Despite anatomical similarities, there appear to be differences in susceptibility to cardiovascular disease between primates. For example, humans are prone to ischemia-induced myocardial infarction unlike chimpanzees, which tend to suffer from fibrotic disease. However, it is challenging to determine the relative contributions of genetic and environmental effects to complex disease phenotypes within and between primates. The ability to differentiate cardiomyocytes from induced pluripotent stem cells (iPSCs), now allows for direct inter-species comparisons of the gene regulatory response to disease-relevant perturbations. A consequence of ischemia is oxygen deprivation. Therefore, in order to understand human-specific regulatory adaptations in the heart, and to potentially gain insight into the evolution of disease susceptibility and resistance, we developed a model of hypoxia in human and chimpanzee cardiomyocytes. We differentiated eight human and seven chimpanzee iPSC lines into cardiomyocytes under normoxic conditions, and subjected these cells to 6 hours of hypoxia, followed by 6 or 24 hours of re-oxygenation. We collected genome-wide gene expression data as well as measurements of cellular stress at each time-point. The overall cellular and transcriptional response to hypoxic stress is generally conserved across species. Supporting the functional importance of precise regulatory response to hypoxia, we found that genes that respond to hypoxic stress in both species are depleted for association with expression quantitative trait loci (eQTLs) in the heart, and cardiovascular-related genes. We also identified hundereds of inter-species regulatory differences in our study. In particular, RASD1, which is associated with coronary artery disease, is up-regulated specifically in humans following hypoxia.
Detecting Large Indels Using Optical Map Data
Authors: Fan Xian , Xu Jie , Nakhleh Luay
Published: August 2018

Optical Maps (OM) provide reads that are very long, and thus can be used to detect large indels not detectable by the shorter reads provided by sequence-based technologies such as Illumina and PacBio. Two existing tools for detecting large indels from OM data are BioNano Solve and OMSV. However, these two tools may miss indels with weak signals. We propose a local-assembly based approach, OMIndel, to detect large indels with OM data. The results of applying OMIndel to empirical data demonstrate that it is able to detect indels with weak signal. Furthermore, compared with the other two OM-based methods, OMIndel has a lower false discovery rate. We also investigated the indels that can only be detected by OM but not Illumina, PacBio or 10X, and we found that they mostly fall into two categories: complex events or indels on repetitive regions. This implies that adding the OM data to sequence-based technologies can provide significant progress towards a more complete characterization of structural variants (SVs). The algorithm has been implemented in Perl and is publicly available onhttps://bitbucket.org/xianfan/optmethod.
Descriptions of four new species ofMinyomerusHorn, 1876 sec. Jansen & Franz, 2018 (Coleoptera: Curculionidae), with notes on their distribution and phylogeny
Authors: Jansen M. Andrew , Franz Nico M.
Published: August 2018

This contribution adopts the taxonomic concept approach, including the use oftaxonomic concept labels(name sec. [according to] source) and Region Connection Calculus (RCC-5) articulations and alignments. Prior to this study, the broad-nosed weevil genusMinyomerusHorn, 1876 sec. Jansen & Franz, 2015 (Curculionidae [non-focal]: Entiminae [non-focal]: Tanymecini [non-focal]) contained 17 species distributed throughout the desert and plains regions of North America. In this review ofMinyomerussec. Jansen & Franz, 2018, we describe the following four species as new to science:Minyomerus ampullaceussec. Jansen & Franz, 2018 (henceforth: [JF2018]),new species,Minyomerus franko[JF2018],new species,Minyomerus sculptilis[JF2018],new species, andMinyomerus tylotos[JF2018],new species. The four new species are added to, and integrated with, the preceding revision, and an updated key and phylogeny ofMinyomerus[JF2018] are presented. A cladistic analysis using 52 morphological characters of 26 terminal taxa (5/21 outgroup/ingroup) yielded a single most-parsimonious cladogram (Length = 99 steps, Consistency Index = 60, Retention Index = 80). The analysis reaffirms the monophyly ofMinyomerus[JF2018] with eight unreversed synapomorphies. The species-group placements, possible biogeographic origins, and natural history of the new species are discussed in detail.
scBASE: A Bayesian mixture model for the analysis of allelic expression in single cells
Authors: Choi Kwangbom , Raghupathy Narayanan , Churchill Gary A.
Published: August 2018

Allele-specific expression (ASE) at single-cell resolution is a critical tool for understanding the stochastic and dynamic features of gene expression. However, low read coverage and high biological variability present challenges for analyzing ASE. We propose a new method for ASE analysis from single cell RNA-Seq data that accurately classifies allelic expression states and improves estimation of allelic proportions by pooling information across cells.
More than black and white: complex relationships involving serine proteases regulate the Toll pathway and the melanization response inDrosophila
Authors: Dudzic J.P. , Hanson M.A. , latsenko I. , Kondo S. , Lemaitre B.
Published: August 2018

The melanization response is a rapid and important defense mechanism in arthropods. Melanin is produced around wound sites and invading microorganisms by phenoloxidases (POs), which need to be activated by the sequential activation of an extracellular serine protease (SP) cascade.Drosophila melanogasterhas been a useful genetic model for dissecting insect immune signaling, but understanding these proteolytic cascades has been complicated by the large number of SP genes, possibly with redundant function. Taking advantage of recently-generated null and compound mutants, we re-investigated the role of SPs involved in the melanization response inD. melanogasterand discovered phenotypes previously concealed in single mutant analysis. We found that two of them, Hayan and Sp7, can activate the melanization response in two different manners: Hayan is required in the local blackening of wound sites, while Sp7 regulates an alternate melanization reaction responsible for the clearance of septic infections withStaphylococcus aureus. We present evidence that both Sp7 and Hayan regulate the Toll NF-kB pathway. Sp7 is regulated by canonical Toll signaling downstream of PGRP-SA, ModSP, and Grass, leading to control of septic infections via a Sp7-dependent melanization response. Additionally, we found that Hayan and the Toll-regulating SP Psh are the result of a recent gene duplication. Using genetic manipulations, we reveal the hidden role for Hayan, alongside Psh, in propagating Toll signaling downstream of pattern recognition receptors. Thus, we describe the existence of two pathways leading to the melanization response and reveal previously unknown dynamics in the activation of the Toll pathway.
Inner lumen proteins stabilize doublet microtubules in cilia/flagella
Authors: Owa Mikito , Uchihashi Takayuki , Yanagisawa Haruaki , Yamano Takashi , Iguchi Hiro , Fukuzawa Hideya , Wakabayashi Ken-ichi , Ando Toshio , Kikkawa Masahide
Published: August 2018

Motile cilia are microtubule-based organelles that play important roles in most eukaryotes. Although it is known that microtubules in cilia are sufficiently stable to withstand their beating motion, it remains unknown how they are stabilized while serving as tracks for axonemal dynein and intraflagellar transport. To address this question, we identified a new class of microtubule-associated proteins, named FAP45 and FAP52, inChlamydomonas. These proteins are conserved among eukaryotes with motile cilia. Using cryo-electron tomography (cryo-ET) and high-speed atomic force microscopy (HS-AFM), we established that lack of these proteins leads to a loss of inner protrusions in B-tubules and less stable microtubules. These inner protrusions are located near the inner junctions of doublet microtubules and lack of FAP45, FAP52, and FAP20 results in detachment of the B-tubule from the A-tubule, as well as flagellar shortening. These results demonstrated that FAP45 and FAP52 bind to the inside of microtubules and stabilize ciliary axonemes.
MicroRNA-27a is a key modulator of cholesterol biosynthesis
Authors: Khan Abrar A. , Agarwal Heena , Reddy S. Santosh , Arige Vikas , Gupta Vinayak , Kalyani Ananthamohan , Barthwal Manoj K. , Mahapatra Nitish R.
Published: August 2018

Hypercholesterolemia is a strong predictor of cardiovascular diseases. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase gene (Hmgcr) coding for the rate-limiting enzyme in the cholesterol biosynthesis pathway is a crucial regulator of plasma cholesterol levels. However, the post-transcriptional regulation of Hmgcr remains poorly understood. The main objective of this study was to explore the role of miRNAs in the regulation ofHmgcrexpression. Systematicin silico predictionsand experimental analyses reveal that miR-27a specifically interacts with theHmgcr3’-untranslated region in murine and human hepatocytes. Moreover, our data shows thatHmgcrexpression is inversely correlated with miR-27a levels in various cultured cell lines, human and rodent tissues. Actinomycin D chase assays and relevant experiments demonstrate that miR-27a regulates Hmgcr by translational attenuation followed by mRNA degradation. Early Growth Response 1 (Egr1) regulates miR-27a expression under basal and cholesterol-modulated conditions. miR-27a augmentation via tail-vein injection of miR-27a mimic in high cholesterol diet-fedApoe−/−mice shows down-regulation of hepatic Hmgcr and plasma cholesterol levels. Pathway and gene expression analyses show that miR-27a also targets several other genes (apart fromHmgcr) in cholesterol biosynthesis pathway. Taken together, miR-27a emerges as a key regulator of cholesterol biosynthesis and has therapeutic potential for clinical management of hypercholesterolemia.
Cholesterol interaction sites on the transmembrane domain of the hedgehog signal transducer and Class F G protein-coupled receptor Smoothened
Authors: Hedger George , Koldsø Heidi , Chavent Matthieu , Siebold Christian , Rohatgi Rajat , Sansom Mark S. P.
Published: August 2018

Transduction of hedgehog signals across the plasma membrane is a key process during animal development. This is facilitated by the Class F G-protein-coupled-receptor (GPCR) Smoothened (SMO), a major drug target in the treatment of basal cell carcinomas. Recent studies have suggested that SMO is modulated via interactions of its transmembrane (TM) domain with cholesterol. Long time scale (>0.35 ms of simulation time) molecular dynamics simulations of SMO embedded in two different cholesterol containing lipid bilayers reveal direct interactions of cholesterol with the transmembrane domain at regions distinct from those observed in Class A GPCRs. In particular the extracellular tips of helices TM2 and TM3 form a well-defined cholesterol interaction site, robust to changes in membrane composition and in force field parameters. Potential of mean force calculations for cholesterol interactions yield a free energy landscape for cholesterol binding. Combined with analysis of equilibrium cholesterol occupancy these results reveal the existence of a dynamic ‘greasy patch’ interaction with the TM domain of SMO, which may be compared to previously identified lipid interaction sites on other membrane proteins. These predictions provide molecular level insights into cholesterol interactions with a biomedically relevant Class F GPCR, suggesting potential druggable sites.