bluuebunny/crossref_metadata_2025 huggingface dataset:
Updates on the neurobiology of food reward and their relation to the obesogenic environment
Authors: Uribe-Cerda Sofia , Morselli Eugenia , Perez-Leighton Claudio
Published: August 2018

Purpose of review

To summarize recent findings about the neurobiological control of food reward and discuss their relevance for hedonic food intake and obesity in our current obesogenic environment.

Recent findings

Recent data show new roles for circuits involving neuronal subpopulations within the central amyglada (CeA) and lateral hypothalamus in the regulation of feeding and reward in rodents under free and operant conditions and also in restrain from reward consumption. Recent work also shows that the orbitofrontal cortex (OFC) codes for subjective perception of food features during reward assessment of individual foods and that activity in the nucleus accumbens (NAc) codes for anticipation for reward, which can be blocked by time-locked neurostimulation of NAc.

New data illustrates that different aspects of hedonic intake and food reward are coded in a distributed brain network. In particular, as our obesogenic environment facilitates access to palatable food and promotes cue-induced feeding, neuronal circuits related to control of impulsivity, food valuation and duration of hedonic intake episodes might have a significant role in our ability to control food intake and development of obesity by excess intake.
Cardiovascular oncology: exploring the effects of targeted cancer therapies on atherosclerosis
Authors: Seijkens Tom T.P. , Lutgens Esther
Published: August 2018

Purpose of review

Targeted cancer therapies have revolutionized the treatment of cancer in the past decade, but cardiovascular toxicity is a rising problem in cancer patients. Here we discuss the effects of targeted cancer therapies on atherosclerosis. Increasing the awareness of these adverse effects will promote the development of evidence-based preventive strategies in the emerging field of cardiovascular oncology.

Recent findings

Vascular endothelial growth factor inhibitors, immunomodulatory imide drugs, tyrosine kinase inhibitors and immune checkpoint inhibitors are successfully used as treatment for many types of solid and hematologic malignancies. However, clinical and experimental studies have demonstrated that these drugs can drive atherosclerosis, thereby causing adverse cardiovascular events such as myocardial infarction, stroke and peripheral arterial occlusive diseases.

In this review, we discuss how on-target and off-target effects of novel cancer drugs may affect atherosclerosis and we postulate how these cardiovascular adverse events can be prevented in the future.
Practices of Introduction of Complementary Feeding and Iron Deficiency Prevention in the Middle East and North Africa
Authors: Lifschitz Carlos H. , Miqdady Mohamad , Indrio Flavia , Haddad Joseph , Tawfik Eslam , AbdelHak Akbari , Mouane Nezha , Salah Mohamed , Khatami Katayoun , Olang Beheshteh , Vandenplas Yvan
Published: August 2018

Background:

Iron deficiency (ID) with or without anemia is associated with impaired mental and psychomotor development. Given the paucity of information on physicians’ knowledge and practices on iron (Fe) supplementation and impact of ID in the Middle East and North Africa, it was felt important to conduct a survey.

Method:

A group of expert physicians developed a questionnaire that was randomly distributed among Middle East and North Africa doctors to assess their knowledge and practices on introduction of complementary feeding, impact of ID, its prevention, and their impression on prevalence of ID. Descriptive statistics were used.

Results:

We received 2444 completed questionnaires. Thirty‐nine percent of physicians do not follow the European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines regarding age of introduction of complementary feedings. Approximately 62% estimate the prevalence of ID anemia to be 40% to 70%; however, only 17% always monitor hemoglobin between 9 and 12 months of age, 43% do so “almost” always, whereas 36% do so “rarely” or (4%) “never.” For the prevention of ID in infants older than 6 months of age, almost all recommend introducing Fe supplements. Ninety‐seven percent agree that untreated ID during infancy may have long‐term negative effects on cognitive function, whereas 53.26% consider that Fe‐enriched infant cereals result in staining of the baby teeth, constipation, and dark stools.

Conclusions:

Although there is awareness of the impact of ID, there are some misconceptions regarding age of introduction of complementary feedings, surveillance of Fe status, and side effects of Fe‐enriched infant cereals. There is a need for educational initiatives focusing on prevention of Fe deficiency.
Absorption and Safety With Sustained Use of RELiZORB Evaluation (ASSURE) Study in Patients With Cystic Fibrosis Receiving Enteral Feeding
Authors: Stevens John , Wyatt Colby , Brown Perry , Patel Dhiren , Grujic Danica , Freedman Steven D.
Published: August 2018

Objectives:

Pancreatic insufficiency (PI) and malabsorption of fats lead to reduced caloric intake, inability to maintain weight, and increased gastrointestinal symptoms. Thus, enteral nutrition (EN) is used in patients with cystic fibrosis (CF) and poor nutritional status. The current study evaluated safety, tolerability, and improvement of fatty acid (FA) status in red blood cell (RBC) membranes, a marker of long‐term FA absorption, with an in‐line digestive cartridge (RELiZORB) that hydrolyzes fat in enteral formula.

Methods:

Patients with CF receiving EN participated in a multicenter, 90‐day open‐label study during which RELiZORB was used with overnight EN. The primary endpoint was change over time in RBC uptake of docosahexaenoic acid (DHA)+ eicosapentaenoic acid (EPA). Gastrointestinal symptoms were collected to evaluate safety and tolerability. Several clinical and anthropometric parameters were also assessed throughout the study.

Results:

A total of 36 subjects completed the study with a mean age of 13.8 years, body mass index of 17.7 and 6.2 years mean use of overnight EN. Fat absorption significantly improved as shown by increased RBC levels of DHA+EPA, improved ω‐6/ω‐3 ratio, and increased plasma levels of DHA+EPA. RELiZORB use was not associated with any unanticipated adverse events.

Conclusions:

RELiZORB use was found to be safe, well tolerated, and resulted in increased levels of FAs in RBCs and plasma. This is the first prospective study to show EN can improve FA abnormalities in CF. Because improvement in omega‐3 levels has been shown to help pulmonary and inflammatory status as well as anthropometric parameters in CF, RELiZORB may have important long‐term therapeutic benefits in patients with CF.
Unexpected High Rates of Persistent Trichomonas vaginalis Infection in a Retrospective Cohort of Treated Pregnant Women
Authors: Lazenby Gweneth B. , Thompson Lauren , Powell Anna M. , Soper David E.
Published: August 2018

Background

Our primary objective was to determine the rate of persistent Trichomonas infection among pregnant women posttreatment. The secondary objective was to determine if oral multidose metronidazole was associated with fewer cases of persistent Trichomonas compared with single-dose treatment.

Methods

This is a retrospective cohort study of women diagnosed with genital Trichomonas vaginalis from 2008 to 2017. We calculated the rate of persistent Trichomonas by dividing the number of positive Trichomonas tests collected 21 days or longer posttreatment by the total number of women treated and retested. Bivariate analysis was performed to compare the rates of positive tests after single and multidose metronidazole. Multivariate logistic regression was used to evaluate factors associated with persistent infection.

Results

Five hundred forty-two women with 565 pregnancies were diagnosed with Trichomonas infection. The majority of subjects were prescribed either single-dose (n = 352) or multidose metronidazole (n = 74). Posttreatment Trichomonas tests were collected 21 days or longer in 326 subjects and 44% (143) were positive. Rates of positive Trichomonas tests among women receiving single-dose and multidose regimens were similar (45% vs. 40%, P = 0.50). Women who had ≥1 pregnancy affected by Trichomonas infection were more likely to have a positive test posttreatment (adjusted odds ratio, 20.1; 95% confidence interval, 1.9–215.3). Obese women were less likely to have a positive test posttreatment (adjusted odds ratio, 0.3; 95% confidence interval, 0.1–0.9).

Conclusions

Given high rates of positive Trichomonas tests and increased detection with nucleic acid amplification tests (NAATs), all pregnant women should be retested with NAATs approximately 3 weeks posttreatment. Further studies are needed to determine the most effective treatment of Trichomonas infection in pregnant women.
Assessment of Visual Acuity in Children Using Crowded Lea Symbol Charts
Authors: Sailoganathan Ananth , Rou Leong Xin , Buja Kenny Anak , Siderov John
Published: August 2018

SIGNIFICANCE

Vision charts comprising single Lea symbols surrounded by either flanking bars or flanking Lea symbols are available for measurement of visual acuity in children. However, the results obtained with such charts may not be interchangeable owing to potential differences in the crowding effect.

PURPOSE

The purpose of this study was to compare habitual visual acuity in a sample of young children using two versions of the single Lea symbols charts with different crowding features.

METHODS

Monocular habitual visual acuity was measured in a sample of 77 young children aged between 4 and 6 years using crowded Lea symbols charts with either flanking bars separated from the central symbol by 0.5 optotype width or flanking Lea optotypes separated from the central symbol by 1.0 optotype width.

RESULTS

Mean visual acuity was higher (i.e., lower logarithm of the minimum angle of resolution) with the Lea symbols crowded using flanking optotypes, equivalent to about 1.5 optotype difference. Visual acuity measured with the two charts was significantly correlated; however, the 95% limits of agreement were larger than expected from repeatability studies using Lea symbols.

CONCLUSIONS

Lea symbols with flanking optotypes resulted in higher visual acuity than the Lea symbols with flanking bars, probably as a result of differences in the crowding effect. The two charts showed insufficient agreement, and we do not recommend their use interchangeably. We recommend using the Lea symbols with flanking bars because of the closer flanker-target separation.
Population Pharmacokinetics of Vancomycin in Pediatric Extracorporeal Membrane Oxygenation*
Authors: Moffett Brady S. , Morris Jennifer , Galati Marianne , Munoz Flor , Arikan Ayse A.
Published: August 2018

Objectives:

Describe the pharmacokinetics of vancomycin in pediatric patients undergoing extracorporeal membrane oxygenation and provide dosing recommendations to attain an area under the curve for 24 hours greater than 400 in this population.

Design:

Retrospective, population pharmacokinetic analysis.

Setting:

PICU of a large tertiary care children’s hospital.

Interventions:

Population pharmacokinetic analysis and simulation were performed with NONMEM v7.3 (Icon, PLC, Dublin, Ireland).

Patients:

Patients less than 19 years old who received IV vancomycin and had serum vancomycin concentration monitoring while undergoing extracorporeal membrane oxygenation from January 1, 2011, to June 30, 2017.

Measurements and Main Results:

A total of 93 patients met study criteria (male 51%, median age 0.64 yr [interquartile range 0.07–6.7 yr]). Mean estimated creatinine clearance was 65 ± 47 mL/min/1.73 m2. Patients received 1,116 vancomycin doses (14.6 ± 1.9 mg/kg/dose) and had 433 vancomycin serum concentrations (13.6 ± 6.9 mg/L) at 13.2 ± 10.7 hours after a dose. A two-compartment pharmacokinetic model with allometrically scaled weight on clearance (0.75) and volumes of distribution (1) was developed. Serum creatinine, postmenstrual age were significant covariates for clearance, patient age for central volume of distribution, and albumin for peripheral volume of distribution. Simulation identified a doses of 25–30 mg/kg/dose every 12–24 hours as having the highest percentage of patients with an area under the curve for 24 hours greater than 400 with the highest percentage trough concentrations in the less than 15 mg/L range.

Conclusions:

A vancomycin dose of 25–30 mg/kg/dose every 12–24 hours with serum concentration monitoring is a reasonable empiric dosing strategy to obtain an area under the curve for 24 hours greater than 400 in pediatric extracorporeal membrane oxygenation patients.
Enteroaggregative Escherichia coli subclinical and clinical infections
Authors: Lima Aldo A.M. , Medeiros Pedro H.Q.S. , Havt Alexandre
Published: August 2018

Purpose of review

The current review is to update the results on epidemiology, pathobiology, and genes related to virulence, clinical presentation, molecular diagnosis, antimicrobial resistance, and extraintestinal infection of enteroaggregativeEscherichia coli(EAEC).

Recent findings

EAEC subclinical infection was significantly associated with reduced length at 2 years of age and EAEC and coinfections were associated with reduced delta weight-for-length and weight-for-agez-scores in the first 6 months of age in the MAL-ED birth cohort study. EAEC was associated with malnutrition in children 6–24 months of age in prospective case–control studies in Bangladesh and Brazil. Virulence gene-based studies have suggested aggregative fimbriae II may be a major contributor to disease, whereas AggR-activated regulator a marker of less severe disease. The high ability of EAEC colonization likely exacerbates effects of other microbial virulence strategies. Molecular diagnosis has been useful for understanding EAEC burden, although different criteria may relate to different pathogenic outcomes.

EAEC gained special interest in the past few years, especially due to association with growth decrements in children with subclinical infections and its important role as a copathogen. Understanding of EAEC pathogenesis advanced but further research is needed for elucidating both microbial and host factors influencing infection outcomes.
Deep Learning in Diagnosis of Maxillary Sinusitis Using Conventional Radiography
Authors: Kim Youngjune , Lee Kyong Joon , Sunwoo Leonard , Choi Dongjun , Nam Chang-Mo , Cho Jungheum , Kim Jihyun , Bae Yun Jung , Yoo Roh-Eul , Choi Byung Se , Jung Cheolkyu , Kim Jae Hyoung
Published: August 2018

Objectives

The aim of this study was to compare the diagnostic performance of a deep learning algorithm with that of radiologists in diagnosing maxillary sinusitis on Waters’ view radiographs.

Materials and Methods

Among 80,475 Waters’ view radiographs, examined between May 2003 and February 2017, 9000 randomly selected cases were classified as normal or maxillary sinusitis based on radiographic findings and divided into training (n = 8000) and validation (n = 1000) sets to develop a deep learning algorithm. Two test sets composed of Waters’ view radiographs with concurrent paranasal sinus computed tomography were labeled based on computed tomography findings: one with temporal separation (n = 140) and the other with geographic separation (n = 200) from the training set. Area under the receiver operating characteristics curve (AUC), sensitivity, and specificity of the algorithm and 5 radiologists were assessed. Interobserver agreement between the algorithm and majority decision of the radiologists was measured. The correlation coefficient between the predicted probability of the algorithm and average confidence level of the radiologists was determined.

Results

The AUCs of the deep learning algorithm were 0.93 and 0.88 for the temporal and geographic external test sets, respectively. The AUCs of the radiologists were 0.83 to 0.89 for the temporal and 0.75 to 0.84 for the geographic external test sets. The deep learning algorithm showed statistically significantly higher AUC than radiologist in both test sets. In terms of sensitivity and specificity, the deep learning algorithm was comparable to the radiologists. A strong interobserver agreement was noted between the algorithm and radiologists (Cohen κ coefficient, 0.82). The correlation coefficient between the predicted probability of the algorithm and confidence level of radiologists was 0.89 and 0.84 for the 2 test sets, respectively.

Conclusions

The deep learning algorithm could diagnose maxillary sinusitis on Waters’ view radiograph with superior AUC and comparable sensitivity and specificity to those of radiologists.
CT Manifestations of Tumor Spread Through Airspaces in Pulmonary Adenocarcinomas Presenting as Subsolid Nodules
Authors: de Margerie-Mellon Constance , Onken Allison , Heidinger Benedikt H. , VanderLaan Paul A. , Bankier Alexander A.
Published: August 2018

Purpose:

The aim of this study was to identify potential computed tomography manifestations of pulmonary adenocarcinomas presenting as subsolid nodules and associated with the histologic evidence of spread of tumor through air spaces (STAS).

Materials and Methods:

From a radiologic-pathologic repository of resected pulmonary adenocarcinomas including 203 subsolid nodules, 40 STAS-positive nodules were randomly selected and matched to 40 STAS-negative nodules. Total average diameter, as well as average and long-axis diameters of the solid component, was measured. The proportion of solid component diameter to total average diameter was calculated. Measurements and proportions between STAS-positive and STAS-negative nodules were compared with paired samples t test, χ2 test, or the Fisher exact test.

Results:

The total average diameter in STAS-positive nodules was significantly larger than in STAS-negative nodules (P=0.024). The average and long-axis diameters of the solid component of STAS-positive nodules were significantly larger than that of STAS-negative nodules (P=0.001 and 0.003). The proportion of solid component to total average diameter was significantly larger in STAS-positive than in STAS-negative nodules (P=0.041). At a threshold of ≥10 mm for the average and the solid component long-axis diameters, significantly more nodules were STAS-positive than STAS-negative (P=0.015 and 0.001).

Conclusions:

Total average diameter, average and long-axis diameters of the solid component, and a high proportion of solid component diameter compared with total average diameter are computed tomography manifestations of subsolid pulmonary adenocarcinomas with STAS. These findings could serve as an in-vivo tool for the likelihood estimation of STAS, and consequently influence management of subsolid adenocarcinomas.
Age-stratified Patterns of Thymic Involution on Multidetector CT
Authors: Drabkin Michael J. , Meyer John I. , Kanth Nalini , Lobel Shari , Fogel Joshua , Grossman Julia , Krumenacker John H.
Published: August 2018

Purpose:

The aim of this study was to better assess the prevalence and appearance of thymic tissue in adults stratified by age using multidetector computed tomography (MDCT) in order to prevent misinterpretation of normal thymic tissue as pathology.

Materials and Methods:

This study examined the CT appearance of the thymus in 597 trauma patients aged 30 to 69 years (M=48.0 y, SD=11.3). Three body fellowship-trained attending radiologists independently reviewed the CT scans. Reviewers assigned one of 5 grades on the basis of the relative proportions of fat and soft tissue in the thymic bed: complete fatty replacement (grade 0), predominantly fat (grade 1), even mix of soft tissue and fat (grade 2), predominantly soft tissue (grade 3), and discrete confluent thymic tissue (grade 4). Objectively, fixed-area region of interest values of the thymic bed were obtained. Interrater reliability was calculated.

Results:

Increased fatty replacement of the thymus occurred with increasing age. We found residual thymic tissue (≥grade 1) in the following age categories: 30 to 39 years (83.0%), 40 to 49 years (71.9%), 50 to 59 years (52.6%), and 60 to 69 years (34.8%). Kappa comparisons for the entire sample were excellent (κ=0.86). Higher grades had higher region of interest values.

Conclusions:

Residual thymic tissue in adults on MDCT is both more prevalent and more prominent than that reported in earlier studies and can be visible into the seventh decade. We recommend that radiologists and clinicians familiarize themselves with the normal range appearances of the thymus on MDCT, in order to prevent misinterpretation of normal thymic tissue as pathology, which may result in unnecessary procedures.
Clinical Impact of Iatrogenic Small Bowel Perforation Secondary to Laparoscopic Cholecystectomy: A Single-center Experience
Authors: Künzli Beat M. , Spohnholz Johannes , Braumann Chris , Shrikhande Shailesh V. , Uhl Waldemar
Published: August 2018

Objective:

Bowel, vascular, and biliary injuries during laparoscopic cholecystectomy (LC) have to be addressed with high priority. The focus of this study was on small bowel injury (SBI) and its impact on clinical management.

Methods:

We report 5 cases of SBI in a retrospective database of 2062 consecutive LC between January 2004 and December 2017.

Results:

We report isolated iatrogenic SBI in 0.24% (5 of 2062) after LC. We identified 3 cases with SBI associated with the technique of Hasson or related problems with intraoperative relaxation toward the end of the LC. All 5 patients needed at least 1 reoperation. There was no mortality in this series and all patients with iatrogenic SBI got discharged from the clinic in good health. Nevertheless, 3 of 5 patients (60%) with SBI filed a law suit.

Conclusions:

Isolated iatrogenic SBI is a rare but dreaded complication after LC with high impact on patient’s health and prone for medicolegal claims. Strict precaution on thorough relaxation throughout the operation, meticulous handling of closing technique of the fascial layer and “eternal vigilance” are mandatory to reduce risks of SBI after LC.
What is the Appropriate Nodular Diameter in Thyroid Cancer for Extraction by Transoral Endoscopic Thyroidectomy Vestibular Approach Without Breaking the Specimens? A Surgicopathologic Study
Authors: Wu Yi-Ju , Chi Shun-Yu , Elsarawy Ahmed , Chan Yi-Chia , Chou Fong-Fu , Lin Yu-Cheng , Wee Sin-Yong , Pan Cheng-Chung , Cheng Ben-Chung , Lin Chih-Che
Published: August 2018

Transoral Endoscopic Thyroidectomy Vestibular Approach (TOETVA) is a novel technique with better cosmetic results. However, extraction of a large malignant thyroid nodule from the central incision of TOETVA necessitates breaking it into pieces to avoid mental nerve injury, a situation that may violate a proper oncological surgery. In this study, we sought the appropriate nodular diameter in thyroid cancer to be removed in an intact status through the central incision of the TOETVA technique. A total of 27 cases of thyroid nodules were operated using the TOETVA technique from Aug 2016 to July 2017. Excluding 10 benign goiters, the specimens of 17 thyroid cancer cases were divided into intact (group T, n=7) and fragmented (group F, n=10), with a median nodular diameter of 18.35 and 30.30 mm, respectively. Receiver operating characteristic (ROC) curve analysis revealed that the safest nodular diameter is 20 mm, with 100% sensitivity and 87.5% specificity.
Breathlessness in the emergency care setting
Authors: Johnson Miriam J. , Hutchinson Ann
Published: August 2018

Purpose of review

Breathlessness is one of the most common reasons for presentation at the emergency department (ED). The present review summarizes work published from 2017, which focuses on the symptom of breathlessness in its own right rather than as a signpost to diagnosis in relation to presentation to the ED.

Recent findings

Seven relevant papers are included in the present review. Five describe the epidemiology of breathlessness presentation showing: a prevalence of approximately 5% all ED presentations, a high likelihood of hospital admission especially for those with heart failure, breathlessness as a predictor of re-presentation. A sixth study described self-management strategies for breathlessness crises used by expert patients in successfully avoiding presentations to the ED. The seventh study reported the validation of the shorter dyspnea severity scale for use in the ED using a mixture of symptom report and clinical observation measures.

Breathlessness is a common presenting feature in the ED and carries clinical outcome significance irrespective of the causative disease. Routine enquiry is needed to identify, assess, and manage breathlessness alongside interventions to stabilize underlying reversible pathologies. Presentation to the ED because of breathlessness should trigger community-based, supported self-management for future episodes of breathlessness crises.
New highly pachyostotic nothosauroid interpreted as a filter-feeding Triassic marine reptile
Authors: de Miguel Chaves Carlos , Ortega Francisco , Pérez-García Adán
Published: August 2018

Two well-preserved specimens of a new eosauropterygian from the Upper Triassic of Central Spain are attributed to a new taxon,
Paludidraco multidentatus
gen. et sp. nov. It is a member of Simosauridae that presents several exclusive characters suggesting a highly specialized trophic adaptation. This discovery increases the already high ecological disparity of the Triassic marine reptiles.
Convergent evolution in the Euarchontoglires
Authors: Morris Philip J. R. , Cobb Samuel N. F. , Cox Philip G.
Published: August 2018

Convergence—the independent evolution of similar phenotypes in distantly related clades—is a widespread and much-studied phenomenon. An often-cited, but hitherto untested, case of morphological convergence is that between the aye-aye and squirrels. The aye-aye (Daubentonia madagascariensis) is a highly unusual lemuriform primate that has evolved a dentition similar to that of rodents: it possesses large, ever-growing incisors which it uses to strip the bark from trees in order to feed on wood-boring beetle larvae. Indeed, such is the similarity that some of the earliest classifications of the aye-aye placed it in the squirrel genusSciurus. Here, we aimed to test the degree of convergence between the skulls and lower jaws of squirrels and the aye-aye. Three-dimensional landmarks were recorded from the crania and mandibles of 46 taxa representing the majority of families in the Euarchontoglires. Results were plotted as phylomorphospaces and convergence measures were calculated. The convergence between squirrels and the aye-aye was shown to be statistically significant for both the cranium and mandible, although the mandibles seem to converge more closely in shape. The convergence may indicate strong functional drivers of morphology in these taxa, i.e. the use of the incisors to produce high bite forces during feeding. Overall, we have shown that this classic case of convergence stands up to quantitative analysis.
It takes two transducins to activate the cGMP-phosphodiesterase 6 in retinal rods
Authors: Qureshi Bilal M. , Behrmann Elmar , Schöneberg Johannes , Loerke Justus , Bürger Jörg , Mielke Thorsten , Giesebrecht Jan , Noé Frank , Lamb Trevor D. , Hofmann Klaus Peter , Spahn Christian M. T. , Heck Martin
Published: August 2018

Among cyclic nucleotide phosphodiesterases (PDEs), PDE6 is unique in serving as an effector enzyme in G protein-coupled signal transduction. In retinal rods and cones, PDE6 is membrane-bound and activated to hydrolyse its substrate, cGMP, by binding of two active G protein α-subunits (Gα*). To investigate the activation mechanism of mammalian rod PDE6, we have collected functional and structural data, and analysed them by reaction–diffusion simulations. Gα* titration of membrane-bound PDE6 reveals a strong functional asymmetry of the enzyme with respect to the affinity of Gα* for its two binding sites on membrane-bound PDE6 and the enzymatic activity of the intermediary 1 : 1 Gα* · PDE6 complex. Employing cGMP and its 8-bromo analogue as substrates, we find that Gα* · PDE6 forms with high affinity but has virtually no cGMP hydrolytic activity. To fully activate PDE6, it takes a second copy of Gα* which binds with lower affinity, forming Gα* · PDE6 · Gα*. Reaction–diffusion simulations show that the functional asymmetry of membrane-bound PDE6 constitutes a coincidence switch and explains the lack of G protein-related noise in visual signal transduction. The high local concentration of Gα* generated by a light-activated rhodopsin molecule efficiently activates PDE6, whereas the low density of spontaneously activated Gα* fails to activate the effector enzyme.
Enhanced
in vitro
biocompatibility and osteogenesis of titanium substrates immobilized with dopamine-assisted superparamagnetic Fe
3
O
4
nanoparticles for hBMSCs
Authors: Huang Zhenfei , Wu Zhihong , Ma Bupeng , Yu Lingjia , He Yu , Xu Derong , Wu Yuanhao , Wang Hai , Qiu Guixing
Published: August 2018

Titanium (Ti) is an ideal bone substitute due to its superior bio-compatibility and remarkable corrosion resistance. However, in order to improve the osteoconduction and osteoinduction capacities in clinical applications, different kinds of surface modifications are typically applied to Ti alloys. In this study, we fabricated a tightly attached polydopamine-assisted Fe
3
O
4
nanoparticle coating on Ti with magnetic properties, aiming to improve the osteogenesis of the Ti substrates. The PDA-assisted Fe
3
O
4
nanoparticle coatings were characterized by scanning electron microscopy, energy dispersive spectroscopy, atomic force microscopy and water contact angle measurements. The cell attachment and proliferation rate of the human bone mesenchymal stem cells (hBMSCs) on the Ti surface significantly improved with the Fe
3
O
4
/PDA coating when compared with the pure Ti without a coating. Furthermore, the results of
in vitro
alkaline phosphatase (ALP) activity at 7 and 14 days and alizarin red S staining at 14 days showed that the Fe
3
O
4
/PDA coating on Ti promoted the osteogenic differentiation of hBMSCs. Moreover, hBMSCs co-cultured with the Fe
3
O
4
/PDA-coated Ti for approximately 14 days also exhibited a significantly higher mRNA expression level of ALP, osteocalcin and runt-related transcription factor-2 (RUNX2). Our
in vitro
results revealed that the present PDA-assisted Fe
3
O
4
nanoparticle surface coating is an innovative method for Ti surface modification and shows great potential for clinical applications.
Resistance is futile: lack of predator switching and a preference for native prey predict the success of an invasive prey species
Authors: Cuthbert Ross N. , Dickey James W. E. , McMorrow Clare , Laverty Ciaran , Dick Jaimie T. A.
Published: August 2018

Invasive species continue to severely impact biodiversity, yet predicting the success or failure of introduced species has remained elusive. In particular, the relationship between community invasibility and native species diversity remains obscure. Here, we apply two traditional ecological concepts that inform prey population stability and hence invasibility. We first show that the native predatory crustaceanGammarus duebeni celticusexhibited similar type II (destabilizing) functional responses (FRs) towards native mayfly prey and invasive amphipod prey, when these prey species were presented separately. However, when the two prey species were presented simultaneously, the predator did not exhibit prey switching, instead consuming disproportionately more native prey than expected from the relative abundance of native and invasive species. These consumptive propensities foster reductions of native prey, while simultaneously limiting biotic resistance against the invasive species by the native predator. Since our theoretical considerations and laboratory results match known field invasion patterns, we advocate the increased consideration of FR and prey switching studies to understand and predict the success of invasive species.
Experimentally induced social threat increases paranoid thinking
Authors: Saalfeld Vanessa , Ramadan Zeina , Bell Vaughan , Raihani Nichola J.
Published: August 2018

The ability to attribute intentions to others is a hallmark of human social cognition but is altered in paranoia. Paranoia is the most common positive symptom of psychosis but is also present to varying degrees in the general population. Epidemiological models suggest that psychosis risk is associated with low social rank and minority status, but the causal effects of status and group affiliation on paranoid thinking remain unclear. We examined whether relative social status and perceived group affiliation, respectively, affect live paranoid thinking using two large-
N
(
N
 = 2030), pre-registered experiments. Interacting with someone from a higher social rank or a political out-group led to an increase in paranoid attributions of harmful intent for ambiguous actions. Pre-existing paranoia predicted a general increase in harmful intent attribution, but there was no interaction with either type of social threat: highly paranoid people showed the same magnitude of increase as non-paranoid people, although from a higher baseline. We conclude social threat in the form of low social status and out-group status affects paranoid attributions, but ongoing paranoia represents a lowered threshold for detecting social threat rather than an impaired reactivity to it.
Radon signals in geological (natural) geogas and in a simultaneous enhanced confined mode simulation experiment
Authors: Steinitz Gideon , Kotlarsky Peter , Piatibratova Oksana
Published: August 2018

An enhanced confined mode (ECM) radon simulation experiment, tested in the laboratory in Jerusalem, was relocated to a subsurface geophysical observatory located 400 km apart, at a depth of 150 m and with a stable temperature. Five gamma sensors are placed around the ECM canister and lead shielding minimizes the influence of natural local gamma radiation. Simultaneous measurement of the geological radon and from radon in the ECM system indicates that the temporal variation of gamma radiation from radon in the ECM system contains annual, multi-day and daily signals, that correspond to signals in the local geological radon. This implies that a common external driver influences the radiation pattern of the geological radon and from radon inside the ECM canister. Once activated at BGO the typical variation pattern of the experimental system occurring in the laboratory changed to that occurring at the observatory. This is interpreted to indicate that the overall style of the temporal patterns of radiation from radon is site dependent. The outcome of this investigation conforms and further substantiates the recent suggestion that a component in solar radiation is driving the annual and daily periodic components in the variation of radon. New geophysical research potential is indicated.
Small-amplitude static periodic patterns at a fluid–ferrofluid interface
Authors: Groves M. D. , Horn J.
Published: August 2018

We establish the existence of static doubly periodic patterns (in particular rolls, squares and hexagons) on the free surface of a ferrofluid near onset of the Rosensweig instability, assuming a general (nonlinear) magnetization law. A novel formulation of the ferrohydrostatic equations in terms of Dirichlet–Neumann operators for nonlinear elliptic boundary-value problems is presented. We demonstrate the analyticity of these operators in suitable function spaces and solve the ferrohydrostatic problem using an analytic version of Crandall–Rabinowitz local bifurcation theory. Criteria are derived for the bifurcations to be sub-, super- or transcritical with respect to a dimensionless physical parameter.
Comment on ‘The cutting of metals by plastic buckling’ by Udupa
et al
.
Authors: Childs T. H. C.
Published: August 2018

In a recent paper on machining annealed copper at a low cutting speed, and at an uncut chip thickness one-tenth of the mean grain size of the copper, Udupa
et al
. (
Proc. R. Soc A
473
, 20160863,
doi:10.1098/rspa.2016.0863
) report chip thicknesses larger than 10 times the uncut thickness and then a new mode of chip formation. Plastic bulging occurs in the surface of the copper ahead of the tool, leading to chip formation by a series of folds. The strain in the chip is less than that expected in a chip formed by shear according to long-standing classical theory. The authors suggest that the foundations of that theory need to be re-examined. In response, continuum mechanics numerical simulations presented here show a continuous transition from the classical condition towards that observed by Udupa
et al
. as the ratio of chip thickness to uncut thickness increases above approximately 7. Bulging is obtained by introducing (approximately) material heterogeneity to the simulations at a grain size scale but whether such heterogeneity is essential for the bulging flows remains an open question.
Phylogenetic and functional evidence suggests that deep-ocean ecosystems are highly sensitive to environmental change and direct human disturbance
Authors: Ashford Oliver S. , Kenny Andrew J. , Barrio Froján Christopher R. S. , Bonsall Michael B. , Horton Tammy , Brandt Angelika , Bird Graham J. , Gerken Sarah , Rogers Alex D.
Published: August 2018

An understanding of the balance of interspecific competition and the physical environment in structuring organismal communities is crucial because those communities structured primarily by their physical environment typically exhibit greater sensitivity to environmental change than those structured predominantly by competitive interactions. Here, using detailed phylogenetic and functional information, we investigate this question in macrofaunal assemblages from Northwest Atlantic Ocean continental slopes, a high seas region projected to experience substantial environmental change through the current century. We demonstrate assemblages to be both phylogenetically and functionally under-dispersed, and thus conclude that the physical environment, not competition, may dominate in structuring deep-ocean communities. Further, we find temperature and bottom trawling intensity to be among the environmental factors significantly related to assemblage diversity. These results hint that deep-ocean communities are highly sensitive to their physical environment and vulnerable to environmental perturbation, including by direct disturbance through fishing, and indirectly through the changes brought about by climate change.
Landscape context shifts the balance of costs and benefits from wildflower borders on multiple ecosystem services
Authors: Grab Heather , Poveda Katja , Danforth Bryan , Loeb Greg
Published: August 2018

In the face of global biodiversity declines driven by agricultural intensification, local diversification practices are broadly promoted to support farmland biodiversity and multiple ecosystem services. The creation of flower-rich habitats on farmland has been subsidized in both the USA and EU to support biodiversity and promote delivery of ecosystem services. Yet, theory suggests that the landscape context in which local diversification strategies are implemented will influence their success. However, few studies have empirically evaluated this theory or assessed the ability to support multiple ecosystem services simultaneously. Here, we evaluate the impact of creating flower-rich habitats in field margins on pollination, pest control, and crop yield over 3 years using a paired design across a landscape gradient. We find general positive effects of natural habitat cover on fruit weight and that flowering borders increase yields by promoting bee visitation to adjacent crops only in landscapes with intermediate natural habitat cover. Flowering borders had little impact on biological control regardless of landscape context. Thus, knowledge of landscape context can be used to target wildflower border placement in areas where they will have the greatest likelihood for success and least potential for increasing pest populations or yield loss in nearby crops.
Urban hubs of connectivity: contrasting patterns of gene flow within and among cities in the western black widow spider
Authors: Miles Lindsay S. , Dyer Rodney J. , Verrelli Brian C.
Published: August 2018

As urbanization drastically alters the natural landscape and generates novel habitats within cities, the potential for changes to gene flow for urban-dwelling species increases. The western black widow spider (
Latrodectus hesperus
) is a medically relevant urban adapter pest species, for which we have previously identified population genetic signatures consistent with urbanization facilitating gene flow, likely due to human-mediated transport. Here, in an analysis of 1.9 million genome-wide SNPs, we contrast broad-scale geographical analyses of 10 urban and 11 non-urban locales with fine-scale within-city analyses including 30 urban locales across the western USA. These hierarchical datasets enable us to test hypotheses of how urbanization impacts multiple urban cities and their genetic connectivity at different spatial scales. Coupled fine-scale and broad-scale analyses reveal contrasting patterns of high and low genetic differentiation among locales within cities as a result of low and high genetic connectivity, respectively, of these cities to the overall population network. We discuss these results as they challenge the use of cities as replicates of urban eco-evolution, and have implications for conservation and human health in a rapidly growing urban habitat.
The role of dietary competition in the origination and early diversification of North American euprimates
Authors: Stroik Laura K. , Schwartz Gary T.
Published: August 2018

The conditions under which early euprimates (adapids and omomyids) originated and evolved is an area of longstanding debate. The leading hypotheses of euprimate origins promulgate diet as a core component of the early evolution of this group, despite the role of dietary competition in euprimate originations never being tested directly. This study compared three competition models (non-competition, competitive displacement, competitive coexistence) with observed patterns of dietary niche overlap, reconstructed from three-dimensional molar morphology, at the time of the euprimate radiation in North America (at the Paleocene–Eocene boundary). Overlap of reconstructed multidimensional dietary niches between euprimates and members of their guild were analysed using a modified MANOVA to establish the nature of the competitive environment surrounding euprimate origins in North America (an immigration event). Results indicated that adapids entered the mammalian guild in the absence of competition, suggesting dietary adaptations that were unique within the community. Conversely, omomyids experienced strong, but transitory, competition with nyctitheriids, suggesting that omomyids possessed the ability to out-compete this group. These results show that adapids and omomyids experienced different competitive scenarios upon their arrival (origination) in North America and confirm the significance of diet (and dietary adaptations) in euprimate origination and early diversification in mammalian communities.
The circadian activity rhythm is reset by nanowatt pulses of ultraviolet light
Authors: Negelspach David C. , Kaladchibachi Sevag , Fernandez Fabian
Published: August 2018

The circadian pacemaker synchronizes to the Earth's rotation by tracking step-by-step changes in illumination that occur as the sun passes the horizon. While twilight progressions of irradiance and colour are considered important stimuli in this process, comparably less thought has been given to the possibility that ultraviolet A (UVA) radiation might actually play a more formative role given its evolutionary significance in shaping 24 h timekeeping. Here, we show that
Drosophila
activity rhythms can be phase-shifted by UVA light at an energy range seated well below that of the visible spectrum. Because the energy threshold for this resetting matches the incident amount of UVA on the human retina at twilight, our results suggest that UVA light has the potential to function as a similar time cue in people.
Central Dicer-miR-103/107 Controls Developmental Switch of POMC Progenitors into NPY Neurons and Impacts Glucose Homeostasis
Authors: Croizier Sophie , Maillard Julien , Bouret Sebastien G
Published: August 2018

Proopiomelanocortin (POMC) neurons are major negative regulators of energy balance. A distinct developmental property of POMC neurons is that they can adopt an orexigenic neuropeptide Y (NPY) phenotype. However, the mechanisms underlying the differentiation of Pomc progenitors remain unknown. Here, we show that the loss of the microRNA (miRNA)- processing enzyme Dicer in POMC neurons causes metabolic defects, an age-dependent decline in the number of Pomc mRNA-expressing cells, and an increased proportion of Pomc progenitors acquiring a NPY phenotype. miRNome microarray screening further identified miR-103/107 as candidates that may be involved in the maturation of Pomc progenitors. In vitro inhibition of miR-103/107 causes a reduction in the number of Pomc-expressing cells and increases the proportion of Pomc progenitors differentiating into NPY neurons. Moreover, in utero silencing of miR-103/107 causes perturbations in glucose homeostasis. Together, these data suggest a role for prenatal miR-103/107 in the maturation of Pomc progenitors and glucose homeostasis.
A Novelin vivoModel of Anaerobic Infection: The Investigation ofClostridium perfringensinGalleria mellonellaLarvae.
Authors: Kay Sammy J , Edwards Joseph R , Brown Joseph C S , Dixon Ronald A
Published: August 2018

Important research progress into the mechanisms ofClostridium perfringensassociated diseases (CPAD) has been slowed by the lack of a reliable infection model. Wax moth larvae (Galleria mellonella) have emerged as a viable alternative to traditional mammalian organisms since they are economic, survive at 37°C and require no specialist equipment. This study aims to establish whetherG. mellonellalarvae can be developed as a viable model for the study of CPAD and their suitability for studying novel treatment strategies. In addition, the study demonstrates a novel time-lapse approach to data collection. Mortality and morbidity rates of larvae challenged with 105CFU ofC. perfringensisolates from various sources were observed over 72h and dose response data obtained using inoculum sizes of 10- 105CFU. Phenoloxidase enzyme activity was investigated as a marker for immune response and tissue burden by histopathological techniques. Results show thatC. perfringensis pathogenic towardsG. mellonellaalthough potency varies between isolates. Infection activates the melanisation pathway resulting in melanin deposition but no increase in enzyme activity was observed. Efficacy of antibiotic therapy (penicillin G, bacitracin, neomycin and tetracycline) administered parenterally loosely correlates with that of in vitro analysis. The findings suggestG. mellonellacan be a useful in vivo model of infection when investigating CPAD. Although they are unlikely to replace traditional mammals they may be useful as a pre-screening assay for virulence ofC.perfringensstrains or as a simple, cheap and rapid in vivo assay in the development and pre-clinical development of novel therapeutics.
RAB6 and microtubules restrict secretion to focal adhesions
Authors: Fourrière L. , Kasri A. , Gareil N. , Bardin S. , Boulanger J. , Sikora R. , Boncompain G. , Miserey-Lenkei S , Perez F. , Goud B.
Published: August 2018

To ensure their homeostasis and sustain differentiated functions, cells continuously transport diverse cargos to various cell compartments and in particular to the cell surface. Secreted proteins are transported along intracellular routes from the endoplasmic reticulum through the Golgi complex before reaching the plasma membrane along microtubule tracks. Using a synchronized secretion assay, we report here that exocytosis does not occur randomly at the cell surface but on localized hotspots juxtaposed to focal adhesions. Although microtubules are involved, the RAB6-dependent machinery plays an essential role. We observed that, irrespective of the transported cargos, most post-Golgi carriers are positive for RAB6 and that its inactivation leads to a broad reduction of protein secretion. RAB6 may thus be a general regulator of post-Golgi secretion.