bluuebunny/crossref_metadata_2025 huggingface dataset:
Abdominal Wall Reconstruction Utilizing the Combination of Absorbable and Permanent Mesh in a Retromuscular Position: A Multicenter Prospective Study
Authors: García‐Ureña Miguel Ángel , López‐Monclús Javier , Cuccurullo Diego , Blázquez Hernando Luis Alberto , García‐Pastor Providencia , Reggio Stefano , Jiménez Cubedo Elena , San Miguel Méndez Carlos , Cruz Cidoncha Arturo , Robin Valle de Lersundi Alvaro
Published: August 2018

Background

Optimal mesh reinforcement for abdominal wall reconstruction (AWR) in complex hernias remains questionable. Use of biologic, absorbable and synthetic meshes has been described. The idea of using an absorbable mesh (AM) under a permanent mesh (PM) in a retromuscular position may help in these challenging situations.

Methods

Between 2011 and 2016, consecutive patients undergoing open AWR utilizing an AM as posterior layer reinforcement and configuration of a large PM were identified in a multicenter prospectively maintained database in four hospitals. Main outcomes included demographics, ventral hernia classifications, perioperative data, complications and recurrences.

Results

A total of 169 complex incisional hernias were analyzed. Mean age was 60.9, with mean body mass index 30.7 (range: 20–46). Location of incisional hernias (IH) was: 80 midline, 59 lateral and 30 midline and lateral. 78% were grade I and II in Ventral Hernia Working Group classification. 52% of patients were discharged with no complication. There were 19% seromas, 13% hematomas, 12% surgical‐site infection and 10% skin dehiscence. Only partial mesh removal was necessary in one patient. After a mean follow‐up of 26 months (range 15–59), there were five (3.2%) recurrences. Reoperations on patients showed a band of fibrosis separating the peritoneum from the PM.

Conclusion

The combination of AM with very large PM in the same retromuscular position in AWR seems to be safe. The efficacy with recurrence rates below 4% in complex midline and lateral IH may be explained by the use of larger PMs that are extended and configured with the support of AMs. Reoperations on patients have confirmed the previous experimental reports on the use of the AM.
Dynamics of Pseudomonas putida biofilms in an upscale experimental framework
Authors: Espeso David R , Martínez-García Esteban , Carpio Ana , de Lorenzo Víctor
Published: August 2018

Exploitation of biofilms for industrial processes requires them to adopt suitable physical structures for rendering them efficient and predictable. While hydrodynamics could be used to control material features of biofilms of the platform strain Pseudomonas putida KT2440 there is a dearth of experimental data on surface-associated growth behavior in such settings. Millimeter scale biofilm patterns formed by its parental strain P. putida mt-2 under different Reynolds numbers (Re) within laminar regime were analyzed using an upscale experimental continuous cultivation assembly. A tile-scan image acquisition process combined with a customized image analysis revealed patterns of dense heterogeneous structures at Re = 1000, but mostly flattened coverings sparsely patched for Re < 400. These results not only fix the somewhat narrow hydrodynamic regime under which P. putida cells form stable coatings on surfaces destined for large-scale processes, but also provide useful sets of parameters for engineering catalytic biofilms based on this important bacterium as a cell factory.
Disulfiram enhanced delivery of orally administered copper into the central nervous system in Menkes disease mouse model
Authors: Hoshina Takao , Nozaki Satoshi , Hamazaki Takashi , Kudo Satoshi , Nakatani Yuka , Kodama Hiroko , Shintaku Haruo , Watanabe Yasuyoshi
Published: August 2018

Introduction

Menkes disease (MD) is an X‐linked recessive disorder caused by dysfunction of a copper‐transporting protein, leading to severe neurodegeneration in early childhood. We investigated whether a lipophilic copper chelator, disulfiram, could enhance copper absorption from the intestine and transport copper across the blood–brain barrier in MD model mice.

Methods

Wild type and MD model mice were pretreated with disulfiram for 30 min before oral administration of 64CuCl2. Each organ was sequentially analyzed for radioactivity with γ counting. Copper uptake into the brain parenchyma was assessed by ex vivo autoradiography.

Results

In wild type mice, orally administered copper was initially detected in the intestine within 2 h, reaching a maximum level in the liver (19.6 ± 3.8 percentage injected dose per gram [%ID/g]) at 6 h. In MD model mice, the copper reached the maximum level in the liver (5.3 ± 1.5 %ID/g) at 4 h, which was lower than that of wild type mice (19.0 ± 7.4 %ID/g) (P < 0.05). Pretreatment of disulfiram in MD model mice increased the copper level in the brain (0.59 ± 0.28 %ID/g) at 24 h compared with MD model mice without disulfiram (0.07 ± 0.05 %ID/g) (P < 0.05). Ex vivo autoradiography revealed that high levels of copper uptake was observed in the cerebral cortex upon disulfiram pretreatment.

Conclusion

Our data demonstrated that disulfiram enhanced the delivery of orally administered copper into the central nervous system in MD model mice. The administration of disulfiram will enable patients to avoid unpleasant subcutaneous copper injection in the future.
Setting the stage for a role of the postsynaptic proteome in inherited neurometabolic disorders
Authors: Bayés Àlex
Published: August 2018

Neurotransmitter diseases are a well‐defined group of metabolic conditions caused, in most instances, by genes specifically expressed in the presynaptic button. Better understanding of presynaptic molecular physiology, both in normal and pathological conditions, should help develop therapeutical strategies. The clinical relevance of the presynapse in inherited metabolic disorders is in glaring contrast with that of the postsynaptic component, which so far does not seem to play a relevant role in these disorders. This is somewhat surprising, as postsynaptic proteins are known to be involved in many nervous system diseases, particularly in neurodevelopmental and psychiatric disorders. The goal of this article is to explore if defects in the sophisticated postsynaptic machinery could also have a role in neurometabolic disorders.
Twenty years of value sensitive design: a review of methodological practices in VSD projects
Authors: Winkler Till , Spiekermann Sarah
Published: August 2018

This article reviews the academic literature (1996–2016) that emerged under value sensitive design (VSD). It investigates those VSD projects that employed the tripartite methodology, examining the use of VSD methodological elements, and illustrating common practices and identifying shortcomings. The article provides advice for VSD researchers on how to complete and enhance their methodological approach as the research community moves forward.
Alone in a Crowd? Parents of Children with Rare Diseases’ Experiences of Navigating the Healthcare System
Authors: Baumbusch Jennifer , Mayer Samara , Sloan‐Yip Isabel
Published: August 2018

A disorder is considered a rare disease if it affects 1 in 2000, hence, while independently unique, collectively, these conditions are quite common. Many rare diseases are diagnosed during childhood, and therefore parents become primary caregivers in addition to their parental role. Despite the prevalence of rare diseases among children, there has been little research focused on parents’ experiences of navigating the healthcare system, a gap we begin to address in this study. Guided by an interpretive description methodology, participants were recruited through online listservs and posting flyers at a pediatric hospital in Western Canada. Sixteen parents (15 mothers and 1 father) participated in in‐depth, semi‐structured interviews between April 2013 and March 2014. Data were analyzed inductively, generating the main study themes. Findings illuminated the challenges parents’ experienced on their child’s diagnostic journey—from seeking, to receiving, to adjusting to the rare disease diagnosis. Following diagnosis, gaps, and barriers to services resulted in parents pursuing services that could support their child’s unique care needs, which often resulted in out‐of‐pocket payments and changes to employment. Parents found peer support, both online and in person, to be an effective resource. This study illustrates the common challenges experienced by parents of children with rare diseases as they navigate the healthcare system. Parents’ role as “expert caregiver” was rarely acknowledged by healthcare providers, pointing to the need to foster more egalitarian relationships. As well, parents were burdened with the additional role of care coordinator, a role that could be filled formally by a healthcare provider. Lastly, peer support was a key resource in terms of information and emotional support for parents who often begin their journey feeling isolated and alone. Policies and programs are needed that validate the invisible care work of parents and ensure adequate formal supports are in place to mitigate potential sources of inequity for these families. Furthermore, genetic counselors can play a key role in ensuring parents’ informational needs are addressed at the time of diagnosis and in connecting families who share common experiences regardless of the rare disease diagnosis.
A Review of Botulinum Toxin A for the Treatment of Neurogenic Bladder
Authors: Cooley Lauren Folgosa , Kielb Stephanie
Published: August 2018

Prior to FDA approval of intradetrusor botulinum toxin (BoTA) injections for the treatment of neurogenic bladder, patients' treatment options were limited to use of pharmacotherapies such as antimuscarinics, alpha blockers, and more recently beta agonists (some off‐label) or invasive interventions including bladder augmentation and urinary diversion procedures. Herein, we provide a comprehensive literature review detailing the salient clinical literature that led to FDA approval of intradetrusor BoTA for neurogenic bladder. Patients with neurogenic detrusor overactivity and detrusor sphincter dyssynergia have been shown in randomized studies to benefit significantly from intradetrusor BoTA injection with regard to the following parameters: improved voided volume, improved bladder pressure and urodynamic parameters, reduced incidence of urinary tract infection, and improved quality of life. Intradetrusor BoTA injection has revolutionized the treatment landscape for patients with neurogenic bladder by providing them with a safe, efficacious, and cost‐effective means to reduce bladder dysfunction, preserve renal function, and reduce the need for invasive, surgical intervention.

Level of Evidence

I
Intuitive versus Algorithmic Triage
Authors: Hart Alexander , Nammour Elias , Mangolds Virginia , Broach John
Published: August 2018

Introduction

The most commonly used methods for triage in mass-casualty incidents (MCIs) rely upon providers to take exact counts of vital signs or other patient parameters. The acuity and volume of patients which can be present during an MCI makes this a time-consuming and potentially costly process.

Hypothesis

This study evaluates and compares the speed of the commonly used Simple Triage and Rapid Treatment (START) triage method with that of an “intuitive triage” method which relies instead upon the abilities of an experienced first responder to determine the triage category of each victim based upon their overall first-impression assessment. The research team hypothesized that intuitive triage would be faster, without loss of accuracy in assigning triage categories.

Methods

Local adult volunteers were recruited for a staged MCI simulation (active-shooter scenario) utilizing local police, Emergency Medical Services (EMS), public services, and government leadership. Using these same volunteers, a cluster randomized simulation was completed comparing START and intuitive triage. Outcomes consisted of the time and accuracy between the two methods.

Results

The overall mean speed of the triage process was found to be significantly faster with intuitive triage (72.18 seconds) when compared to START (106.57 seconds). This effect was especially dramatic for Red (94.40 vs 138.83 seconds) and Yellow (55.99 vs 91.43 seconds) patients. There were 17 episodes of disagreement between intuitive triage and START, with no statistical difference in the incidence of over- and under-triage between the two groups in a head-to-head comparison.

Conclusion:

Significant time may be saved using the intuitive triage method. Comparing START and intuitive triage groups, there was a very high degree of agreement between triage categories. More prospective research is needed to validate these results.

HartA, NammourE, MangoldsV, BroachJ. Intuitive versus algorithmic triagePrehosp Disaster Med.2018;33(4):355–361.
Seven Decades of Disasters: A Systematic Review of the Literature
Authors: Smith Erin C. , Burkle Frederick M. , Aitken Peter , Leggatt Peter
Published: August 2018

Introduction

The impact of disasters and large-scale crises continues to increase around the world. To mitigate the potential disasters that confront humanity in the new millennium, an evidence-informed approach to disaster management is needed. This study provides the platform for such an evidence-informed approach by identifying peer-reviewed disaster management publications from 1947 through July 2017.

Methods

Peer-reviewed disaster management publications were identified using a comprehensive search of: MEDLINE (US National Library of Medicine, National Institutes of Health; Bethesda, Maryland USA); CINAHL (EBSCO Information Services; Ipswich, Massachusetts USA); EMBASE (Elsevier; Amsterdam, Netherlands); PsychInfo (American Psychological Association; Washington DC, USA); and the Cochrane Library (The Cochrane Collaboration; Oxford, United Kingdom).

Results

A total of 9,433 publications were identified. The publications were overwhelmingly descriptive (74%) while 18% of publications reported the use of a quantitative methodology and eight percent used qualitative methodologies. Only eight percent of these publications were classified as being high-level evidence. The publications were published in 918 multi-disciplinary journals. The journal Prehospital and Disaster Medicine (World Association for Disaster and Emergency Medicine; Madison, Wisconsin USA) published the greatest number of disaster-management-related publications (9%). Hurricane Katrina (2005; Gulf Coast USA) had the greatest number of disaster-specific publications, followed by the September 11, 2001 terrorist attacks (New York, Virginia, and Pennsylvania USA). Publications reporting on the application of objective evaluation tools or frameworks were growing in number.

Conclusion:

The “science” of disaster management is spread across more than 900 different multi-disciplinary journals. The existing evidence-base is overwhelmingly descriptive and lacking in objective, post-disaster evaluations.

SmithEC, BurkleFMJr, AitkenP, LeggattP. Seven decades of disasters: a systematic review of the literature. Prehosp Disaster Med. 2018;33(4):418–423
Subjects and Scholars’ Views on the Ethics of Political Science Field Experiments
Authors: Desposato Scott
Published: August 2018

Recent controversies raise questions regarding the ethics of political science field experiments. I present here results from a public opinion survey in which subjects and scholars evaluated the acceptability of two hypothetical field experiments. In the survey, the designs were randomly varied to identify the most controversial features. Both scholars and subjects reacted negatively to deception and to experiments without informed consent, especially when the research aims were normatively ambiguous. In some cases, half of the respondents reported that they would rather not be in a typical field experiment without their consent.
How and Why Armed Groups Participate in Elections
Authors: Matanock Aila M. , Staniland Paul
Published: August 2018

Armed actors are often involved in electoral politics, from the fusing of ballots and bullets in armed political parties to insurgents covertly backing politicians. We develop new concepts and theory to better understand these complex relationships between violent actors and democratic practice. We first offer a novel conceptualization of armed groups’ electoral strategies that systematically maps out variation in the organizational directness and public openness of groups’ involvement in elections. We then use comparative case studies to develop theory about the conditions under which each of these electoral strategies is most likely, and what can trigger changes between them. The interaction of armed groups’ power and expectations of popular support with governments’ policies of toleration or repression determines the strategies of electoral participation that groups pursue. These concepts and arguments lay the foundation for a systematic research agenda on when and how “normal” and armed politics become intertwined.
Keeping Vigil: The Emergence of Vigilance Committees in Pre-Civil War America
Authors: Obert Jonathan , Mattiacci Eleonora
Published: August 2018

What explains the emergence of organized private enforcement in the United States? We study the formation of vigilance committees—that is, coercive groups organized in a manner not officially sanctioned by state law and with the purpose of establishing legal and moral claims. We argue that these committees were primarily intended to help create civic political identities in contexts of social ambiguity and institutional instability, what we call social frontiers. Relying on quantitative and qualitative analysis, we find that these committees were more likely to form in contexts where levels of ethno-nationalist heterogeneity were high and where political institutions had recently changed. Contrary to common wisdom, vigilance committees were much more than functionalist alternatives to an absent state, or local orders established by bargaining, or responses to social or economic conflict. They constituted flexible instruments to counteract environments characterized by social and political uncertainty.
Effect of Fall-Applied Residual Herbicides on Rice Growth and Yield
Authors: Lawrence Benjamin H. , Bond Jason A. , Edwards Henry M. , Golden Bobby R. , Montgomery Garret B. , Eubank Thomas W. , Walker Timothy W.
Published: August 2018

Glyphosate-resistant (GR) Italian ryegrass is one of the most troublesome weeds in Mississippi row crop production. Fall-applied residual herbicide applications are recommended for control of GR Italian ryegrass. However, carryover of residual herbicides applied in fields for rice production can have a negative impact on rice performance. Field studies were conducted in Stoneville, MS, to determine the effects of fall-applied residual herbicides on rice growth and yield. Herbicide treatments included suggested use rates (1×) of clomazone at 840 g ai ha–1, pyroxasulfone 170 g ai ha–1,S-metolachlor 1,420 g ai ha–1, and trifluralin 1,680 g ai ha–1, and two times (2×) the suggested use rates in the fall before rice seeding. Pooled across application rate, pyroxasulfone,S-metolachlor, and trifluralin injured rice to an extent 28% to 36% greater than clomazone 14 d after emergence (DAE). Rice seedling density and height 14 DAE and rice maturity were negatively affected by all fall-applied herbicides except clomazone. Applications at 2× rates reduced rough rice yields in plots treated with pyroxasulfone,S-metolachlor, and trifluralin compared with clomazone. Pyroxasulfone applied at the 2× rate reduced rough rice yield 22% compared with the 1× rate. Rough rice yield was 90% or greater of the nontreated control in plots treated with either rate ofS-metolachlor, and these were comparable with rough rice yields from plots treated with both rates of trifluralin and the 1× rate of pyroxasulfone. Early-season injury and reductions in seedling density and height 14 DAE, would preclude even 1× applications of pyroxasulfone,S-metolachlor, and trifluralin from being viable options for residual herbicide treatments targeting GR Italian ryegrass in the fall before rice seeding. Of the herbicides evaluated, only clomazone should be utilized as a fall-applied residual herbicide treatment targeting GR Italian ryegrass before seeding rice.
Thermometry of photosensitive and optically induced electrokinetics chips
Authors: Wang Feifei , Liu Lianqing , Li Gongxin , Li Pan , Wen Yangdong , Zhang Guanglie , Wang Yuechao , Lee Gwo-Bin , Li Wen Jung
Published: August 2018

Optically induced electrokinetics (OEK)-based technologies, which integrate the high-resolution dynamic addressability of optical tweezers and the high-throughput capability of electrokinetic forces, have been widely used to manipulate, assemble, and separate biological and non-biological entities in parallel on scales ranging from micrometers to nanometers. However, simultaneously introducing optical and electrical energy into an OEK chip may induce a problematic temperature increase, which poses the potential risk of exceeding physiological conditions and thus inducing variations in cell behavior or activity or even irreversible cell damage during bio-manipulation. Here, we systematically measure the temperature distribution and changes in an OEK chip arising from the projected images and applied alternating current (AC) voltage using an infrared camera. We have found that the average temperature of a projected area is influenced by the light color, total illumination area, ratio of lighted regions to the total controlled areas, and amplitude of the AC voltage. As an example, optically induced thermocapillary flow is triggered by the light image-induced temperature gradient on a photosensitive substrate to realize fluidic hydrogel patterning. Our studies show that the projected light pattern needs to be properly designed to satisfy specific application requirements, especially for applications related to cell manipulation and assembly.
Deep reefs of the Great Barrier Reef offer limited thermal refuge during mass coral bleaching
Authors: Frade Pedro R. , Bongaerts Pim , Englebert Norbert , Rogers Alice , Gonzalez-Rivero Manuel , Hoegh-Guldberg Ove
Published: August 2018

Our rapidly warming climate is threatening coral reefs as thermal anomalies trigger mass coral bleaching events. Deep (or “mesophotic”) coral reefs are hypothesised to act as major ecological refuges from mass bleaching, but empirical assessments are limited. We evaluated the potential of mesophotic reefs within the Great Barrier Reef (GBR) and adjacent Coral Sea to act as thermal refuges by characterising long-term temperature conditions and assessing impacts during the 2016 mass bleaching event. We found that summer upwelling initially provided thermal relief at upper mesophotic depths (40 m), but then subsided resulting in anomalously warm temperatures even at depth. Bleaching impacts on the deep reefs were severe (40% bleached and 6% dead colonies at 40 m) but significantly lower than at shallower depths (60–69% bleached and 8–12% dead at 5-25 m). While we confirm that deep reefs can offer refuge from thermal stress, we highlight important caveats in terms of the transient nature of the protection and their limited ability to provide broad ecological refuge.
Selective conversion of CO2 and H2 into aromatics
Authors: Ni Youming , Chen Zhiyang , Fu Yi , Liu Yong , Zhu Wenliang , Liu Zhongmin
Published: August 2018

Transformation of greenhouse gas CO2 and renewable H2 into fuels and commodity chemicals is recognized as a promising route to store fluctuating renewable energy. Although several C1 chemicals, olefins, and gasoline have been successfully synthesized by CO2 hydrogenation, selective conversion of CO2 and H2 into aromatics is still challenging due to the high unsaturation degree and complex structures of aromatics. Here we report a composite catalyst of ZnAlOx and H-ZSM-5 which yields high aromatics selectivity (73.9%) with extremely low CH4 selectivity (0.4%) among the carbon products without CO. Methanol and dimethyl ether, which are synthesized by hydrogenation of formate species formed on ZnAlOx surface, are transmitted to H-ZSM-5 and subsequently converted into olefins and finally aromatics. Furthermore, 58.1% p-xylene in xylenes is achieved over the composite catalyst containing Si-H-ZSM-5. ZnAlOx&H-ZSM-5 suggests a promising application in manufacturing aromatics from CO2 and H2.
Non-competitive resource exploitation within mosquito shapes within-host malaria infectivity and virulence
Authors: Costa G. , Gildenhard M. , Eldering M. , Lindquist R. L. , Hauser A. E. , Sauerwein R. , Goosmann C. , Brinkmann V. , Carrillo-Bustamante P. , Levashina E. A.
Published: August 2018

Malaria is a fatal human parasitic disease transmitted by a mosquito vector. Although the evolution of within-host malaria virulence has been the focus of many theoretical and empirical studies, the vector’s contribution to this process is not well understood. Here, we explore how within-vector resource exploitation would impact the evolution of within-host Plasmodium virulence. By combining within-vector dynamics and malaria epidemiology, we develop a mathematical model, which predicts that non-competitive parasitic resource exploitation within-vector restricts within-host parasite virulence. To validate our model, we experimentally manipulate mosquito lipid trafficking and gauge within-vector parasite development and within-host infectivity and virulence. We find that mosquito-derived lipids determine within-host parasite virulence by shaping development (quantity) and metabolic activity (quality) of transmissible sporozoites. Our findings uncover the potential impact of within-vector environment and vector control strategies on the evolution of malaria virulence.
The effect of maternal care on gene expression and DNA methylation in a subsocial bee
Authors: Arsenault Samuel V. , Hunt Brendan G. , Rehan Sandra M.
Published: August 2018

Developmental plasticity describes the influence of environmental factors on phenotypic variation. An important mediator of developmental plasticity in many animals is parental care. Here, we examine the consequences of maternal care on offspring after the initial mass provisioning of brood in the small carpenter bee,Ceratina calcarata. Removal of the mother during larval development leads to increased aggression and avoidance in adulthood. This corresponds with changes in expression of over one thousand genes, alternative splicing of hundreds of genes, and significant changes to DNA methylation. We identify genes related to metabolic and neuronal functions that may influence developmental plasticity and aggression. We observe no genome-wide association between differential DNA methylation and differential gene expression or splicing, though indirect relationships may exist between these factors. Our results provide insight into the gene regulatory context of DNA methylation in insects and the molecular avenues through which variation in maternal care influences developmental plasticity.
NCK-dependent pericyte migration promotes pathological neovascularization in ischemic retinopathy
Authors: Dubrac Alexandre , Künzel Steffen E. , Künzel Sandrine H. , Li Jinyu , Chandran Rachana Radhamani , Martin Kathleen , Greif Daniel M. , Adams Ralf H. , Eichmann Anne
Published: August 2018

Pericytes are mural cells that surround capillaries and control angiogenesis and capillary barrier function. During sprouting angiogenesis, endothelial cell-derived platelet-derived growth factor-B (PDGF-B) regulates pericyte proliferation and migration via the platelet-derived growth factor receptor-β (PDGFRβ). PDGF-B overexpression has been associated with proliferative retinopathy, but the underlying mechanisms remain poorly understood. Here we show that abnormal, α-SMA-expressing pericytes cover angiogenic sprouts and pathological neovascular tufts (NVTs) in a mouse model of oxygen-induced retinopathy. Genetic lineage tracing demonstrates that pericytes acquire α-SMA expression during NVT formation. Pericyte depletion through inducible endothelial-specific knockout of Pdgf-b decreases NVT formation and impairs revascularization. Inactivation of the NCK1 and NCK2 adaptor proteins inhibits pericyte migration by preventing PDGF-B-induced phosphorylation of PDGFRβ at Y1009 and PAK activation. Loss of Nck1 and Nck2 in mural cells prevents NVT formation and vascular leakage and promotes revascularization, suggesting PDGFRβ-Y1009/NCK signaling as a potential target for the treatment of retinopathies.
Mechanical interactions among followers determine the emergence of leaders in migrating epithelial cell collectives
Authors: Vishwakarma Medhavi , Di Russo Jacopo , Probst Dimitri , Schwarz Ulrich S. , Das Tamal , Spatz Joachim P.
Published: August 2018

Regulating the emergence of leaders is a central aspect of collective cell migration, but the underlying mechanisms remain ambiguous. Here we show that the selective emergence of leader cells at the epithelial wound-margin depends on the dynamics of the follower cells and is spatially limited by the length-scale of collective force transduction. Owing to the dynamic heterogeneity of the monolayer, cells behind the prospective leaders manifest locally increased traction and monolayer stresses much before these leaders display any phenotypic traits. Followers, in turn, pull on the future leaders to elect them to their fate. Once formed, the territory of a leader can extend only to the length up-to which forces are correlated, which is similar to the length up-to which leader cells can transmit forces. These findings provide mechanobiological insight into the hierarchy in cell collectives during epithelial wound healing.
LRRK2 kinase regulates α-synuclein propagation via RAB35 phosphorylation
Authors: Bae Eun-Jin , Kim Dong-Kyu , Kim Changyoun , Mante Michael , Adame Anthony , Rockenstein Edward , Ulusoy Ayse , Klinkenberg Michael , Jeong Ga Ram , Bae Jae Ryul , Lee Cheolsoon , Lee He-Jin , Lee Byung-Dae , Di Monte Donato A. , Masliah Eliezer , Lee Seung-Jae
Published: August 2018

Propagation of α-synuclein aggregates has been suggested as a contributing factor in Parkinson’s disease (PD) progression. However, the molecular mechanisms underlying α-synuclein aggregation are not fully understood. Here, we demonstrate in cell culture, nematode, and rodent models of PD that leucine-rich repeat kinase 2 (LRRK2), a PD-linked kinase, modulates α-synuclein propagation in a kinase activity-dependent manner. The PD-linked G2019S mutation in LRRK2, which increases kinase activity, enhances propagation efficiency. Furthermore, we show that the role of LRRK2 in α-synuclein propagation is mediated by RAB35 phosphorylation. Constitutive activation of RAB35 overrides the reduced α-synuclein propagation phenotype inlrk-1mutantC. elegans. Finally, in a mouse model of synucleinopathy, administration of an LRRK2 kinase inhibitor reduced α-synuclein aggregation via enhanced interaction of α-synuclein with the lysosomal degradation pathway. These results suggest that LRRK2-mediated RAB35 phosphorylation is a potential therapeutic target for modifying disease progression.
Molecular insights into Vibrio cholerae’s intra-amoebal host-pathogen interactions
Authors: Van der Henst Charles , Vanhove Audrey Sophie , Drebes Dörr Natália Carolina , Stutzmann Sandrine , Stoudmann Candice , Clerc Stéphanie , Scrignari Tiziana , Maclachlan Catherine , Knott Graham , Blokesch Melanie
Published: August 2018

Vibrio cholerae, which causes the diarrheal disease cholera, is a species of bacteria commonly found in aquatic habitats. Within such environments, the bacterium must defend itself against predatory protozoan grazers. Amoebae are prominent grazers, with Acanthamoeba castellanii being one of the best-studied aquatic amoebae. We previously showed that V. cholerae resists digestion by A. castellanii and establishes a replication niche within the host’s osmoregulatory organelle. In this study, we decipher the molecular mechanisms involved in the maintenance of V. cholerae’s intra-amoebal replication niche and its ultimate escape from the succumbed host. We demonstrate that minor virulence features important for disease in mammals, such as extracellular enzymes and flagellum-based motility, have a key role in the replication and transmission of V. cholerae in its aqueous environment. This work, therefore, describes new mechanisms that provide the pathogen with a fitness advantage in its primary habitat, which may have contributed to the emergence of these minor virulence factors in the species V. cholerae.
Controlling electric potential to inhibit solid-electrolyte interphase formation on nanowire anodes for ultrafast lithium-ion batteries
Authors: Chang Won Jun , Kim Su Han , Hwang Jiseon , Chang Jinho , Yang Dong won , Kwon Sun Sang , Kim Jin Tae , Lee Won Woo , Lee Jae Hyung , Park Hyunjung , Song Taeseup , Lee In-Hwan , Whang Dongmok , Il Park Won
Published: August 2018

With increasing demand for high-capacity and rapidly rechargeable anodes, problems associated with unstable evolution of a solid-electrolyte interphase on the active anode surface become more detrimental. Here, we report the near fatigue-free, ultrafast, and high-power operations of lithium-ion battery anodes employing silicide nanowires anchored selectively to the inner surface of graphene-based micro-tubular conducting electrodes. This design electrically shields the electrolyte inside the electrode from an external potential load, eliminating the driving force that generates the solid-electrolyte interphase on the nanowire surface. Owing to this electric control, a solid-electrolyte interphase develops firmly on the outer surface of the graphene, while solid-electrolyte interphase-free nanowires enable fast electronic and ionic transport, as well as strain relaxation over 2000 cycles, with 84% capacity retention even at ultrafast cycling (>20C). Moreover, these anodes exhibit unprecedentedly high rate capabilities with capacity retention higher than 88% at 80C (vs. the capacity at 1C).
Angiopep-2/IP10-EGFRvIIIscFv modified nanoparticles and CTL synergistically inhibit malignant glioblastoma
Authors: Wang Xuan , Xiong Zhiyong , Liu Zhen , Huang Xing , Jiang Xiaobing
Published: August 2018

Preparation of agents that can successfully traverse the blood-brain-barrier (BBB) is a key challenge in brain cancer therapeutics. In this study, angiopep-2 was used as a brain-targeting peptide for preparing multifunctional Angiopep-2-modified poly nanoparticles, angiopep-2 and IP10-EGFRvIIIscFv fusion protein modified nanoparticles. In vitro experiments showed a greater uptake of Angiopep-2 modified nanoparticles, also angiopep-2 and IP10-EGFRvIIIscFv fusion protein modified nanoparticles by bEnd.3 cells versus nanoparticles and nanoparticles modified by IP10-EGFRvIIIscFv. Angiopep-2 and IP10-EGFRvIIIscFv fusion protein modified nanoparticles accumulated in brain tissue after intravenous injection and recruited activated CD8+ T lymphocytes to location of glioblastoma cells. In vivo experiments to assess anti-glioblastoma effect of angiopep-2 and IP10-EGFRvIIIscFv fusion protein modified nanoparticles showed significantly reduced tumor volume in angiopep-2 and IP10-EGFRvIIIscFv fusion protein modified nanoparticles+ CD8+ cytotoxic T lymphocytes group versus in NPs modified by IP10-EGFRvIIIscFv+ CD8+ cytotoxic T lymphocytes, CD8+ cytotoxic T lymphocytes, Angiopep-2 modified nanoparticles+ CD8+ cytotoxic T lymphocytes, angiopep-2 and IP10-EGFRvIIIscFv fusion protein modified nanoparticles and PBS groups. Leukocytes infiltrated in brain tissues showed strong anti-glioblastoma activity in angiopep-2 and IP10-EGFRvIIIscFv fusion protein modified nanoparticles+ CD8+ cytotoxic T lymphocytes treated mice. Thus, angiopep-2 and IP10-EGFRvIIIscFv fusion protein modified nanoparticles may be useful for brain-targeted delivery and recruitment of activated CD8+ T lymphocytes to glioblastoma cells.
The fastest animals and vehicles are neither the biggest nor the fastest over lifetime
Authors: Bejan A. , Gunes U. , Charles J. D. , Sahin B.
Published: August 2018

Here we show how the size of a body affects its maximum average speed of movement through its environment. The theoretical challenge was to predict that ‘outliers’ must exist, such as the cheetah for terrestrial animals and the jet fighter for airplanes. We show that during a travel that starts from rest and continues at cruising speed, the body size for minimum travel time, or maximum average speed, is not the biggest. The results are compared with extensive data for military aircraft for chase, attack and reconnaissance, in addition to data for commercial aircraft. The paper also explains why in earlier studies of flying (animals, airplanes) the airplane data deviated upward (toward greater speeds) relative to the theoretical trend followed by flying animals, and why the fastest animal flyers are one thousand times smaller than the fastest swimmers. Unlike the biggest animals and airplanes (elephant, whale, commercial jet), which move constantly, the fastest animals and airplanes spend most of their lives at rest. When judged for speed averaged over lifetime, the fastest ‘sprinters’ are in fact the slowest movers (as in Aesop’s fable ‘The Tortoise and the Hare’).
Using Two-dimensional Principal Component Analysis and Rotation Forest for Prediction of Protein-Protein Interactions
Authors: Wang Lei , You Zhu-Hong , Yan Xin , Xia Shi-Xiong , Liu Feng , Li Li-Ping , Zhang Wei , Zhou Yong
Published: August 2018

The interaction among proteins is essential in all life activities, and it is the basis of all the metabolic activities of the cells. By studying the protein-protein interactions (PPIs), people can better interpret the function of protein, decoding the phenomenon of life, especially in the design of new drugs with great practical value. Although many high-throughput techniques have been devised for large-scale detection of PPIs, these methods are still expensive and time-consuming. For this reason, there is a much-needed to develop computational methods for predicting PPIs at the entire proteome scale. In this article, we propose a new approach to predict PPIs using Rotation Forest (RF) classifier combine with matrix-based protein sequence. We apply the Position-Specific Scoring Matrix (PSSM), which contains biological evolution information, to represent protein sequences and extract the features through the two-dimensional Principal Component Analysis (2DPCA) algorithm. The descriptors are then sending to the rotation forest classifier for classification. We obtained 97.43% prediction accuracy with 94.92% sensitivity at the precision of 99.93% when the proposed method was applied to the PPIs data of yeast. To evaluate the performance of the proposed method, we compared it with other methods in the same dataset, and validate it on an independent datasets. The results obtained show that the proposed method is an appropriate and promising method for predicting PPIs.
Efficient production of a mature and functional gamma secretase protease
Authors: Khan Imran , Krishnaswamy Sudarsan , Sabale Miheer , Groth David , Wijaya Linda , Morici Michael , Berger Imre , Schaffitzel Christiane , Fraser Paul E. , Martins Ralph N. , Verdile Giuseppe
Published: August 2018

Baculoviral protein expression in insect cells has been previously used to generate large quantities of a protein of interest for subsequent use in biochemical and structural analyses. The MultiBac baculovirus protein expression system has enabled, the use of a single baculovirus to reconstitute a protein complex of interest, resulting in a larger protein yield. Using this system, we aimed to reconstruct the gamma (γ)-secretase complex, a multiprotein enzyme complex essential for the production of amyloid-β (Aβ) protein. A MultiBac vector containing all components of the γ-secretase complex was generated and expression was observed for all components. The complex was active in processing APP and Notch derived γ-secretase substrates and proteolysis could be inhibited with γ-secretase inhibitors, confirming specificity of the recombinant γ-secretase enzyme. Finally, affinity purification was used to purify an active recombinant γ-secretase complex. In this study we demonstrated that the MultiBac protein expression system can be used to generate an active γ-secretase complex and provides a new tool to study γ-secretase enzyme and its variants.
Heterologous production of the widely used natural food colorant carminic acid in Aspergillus nidulans
Authors: Frandsen Rasmus J. N. , Khorsand-Jamal Paiman , Kongstad Kenneth T. , Nafisi Majse , Kannangara Rubini M. , Staerk Dan , Okkels Finn T. , Binderup Kim , Madsen Bjørn , Møller Birger Lindberg , Thrane Ulf , Mortensen Uffe H.
Published: August 2018

The natural red food colorants carmine (E120) and carminic acid are currently produced from scale insects. The access to raw material is limited and current production is sensitive to fluctuation in weather conditions. A cheaper and more stable supply is therefore desirable. Here we present the first proof-of-concept of heterologous microbial production of carminic acid in Aspergillus nidulans by developing a semi-natural biosynthetic pathway. Formation of the tricyclic core of carminic acid is achieved via a two-step process wherein a plant type III polyketide synthase (PKS) forms a non-reduced linear octaketide, which subsequently is folded into the desired flavokermesic acid anthrone (FKA) structure by a cyclase and a aromatase from a bacterial type II PKS system. The formed FKA is oxidized to flavokermesic acid and kermesic acid, catalyzed by endogenous A. nidulans monooxygenases, and further converted to dcII and carminic acid by the Dactylopius coccus C-glucosyltransferase DcUGT2. The establishment of a functional biosynthetic carminic acid pathway in A. nidulans serves as an important step towards industrial-scale production of carminic acid via liquid-state fermentation using a microbial cell factory.
Molecular and physiological responses in roots of two full-sib poplars uncover mechanisms that contribute to differences in partial submergence tolerance
Authors: Peng YanJie , Zhou ZhiXiang , Zhang Zhe , Yu XiaoLi , Zhang XinYe , Du KeBing
Published: August 2018

Poplar is a major afforestation tree species in flood-prone areas. Here, we compared molecular and physiological responses in the roots of two full-sib poplar clones, LS1 (flood-tolerant) and LS2 (flood-susceptive), subjected to stagnant flooding using transcript and metabolite profiling. LS1 displayed less phenotypic damage and superior leaf gas exchange and plant growth compared with those of LS2. We concluded that three characteristics might contribute to the differences in flood tolerance between LS1 and LS2. First, fermentation was initiated through lactic dehydrogenation in LS1 roots under flooding and subsequently dominated by alcohol fermentation. However, lactic dehydrogenase was persistently active in flooded LS2. Second, 13 differentially expressed genes associated with energy and O2consumption processes under soil flooding had lower transcript levels in LS1 than those in LS2, which might contribute to better energy-/O2-saving abilities and behaviours in flood-tolerant LS1 than those in flood-susceptible LS2 under hypoxic stress. Third, LS1 possessed increased reactive oxygen species scavenging abilities compared with those of LS2 under edaphic flooding. Our data are a valuable contribution to understanding the mechanisms involved in the flood tolerance of poplar.
Sensing and Impedance Characteristics of YbTaO4 Sensing Membranes
Authors: Pan Tung-Ming , Huang Yu-Shu , Her Jim-Long
Published: August 2018

In this study we developed ytterbium tantalum oxide (YbTaO4) sensing membranes for use in electrolyte–insulator–semiconductor (EIS) pH sensors. The influence of rapid thermal annealing (RTA) treatment on the sensing and impedance properties of the YbTaO4 sensing membranes deposited through reactive co-sputtering onto Si substrates was explored. X-ray diffraction, atomic force microscopy, and X-ray photoelectron spectroscopy revealed the structural, morphological, and chemical features, respectively, of these YbTaO4 films annealed at 700, 800 and 900 °C. The YbTaO4 EIS device annealed at the 800 °C exhibited a super-Nernstian response of 71.17 mV/pH within the pH range of 2–12. It also showed the lowest hysteresis voltage ( < 1 mV) and the lowest drift rate (0.22 mV/h) among the tested systems. Presumably, the optimal annealing temperature improved the stoichiometry of YbTaO4 film and increased its (−131)-oriented nanograin size. Moreover, the impedance properties of YbTaO4 EIS sensors were investigated by using the capacitance–voltage method. The resistance and capacitance of YbTaO4 sensing films annealed at three various temperatures were evaluated by using different frequency ranges in accumulation, depletion, and inversion regions. The semicircle diameter of the YbTaO4 EIS sensor became smaller, due to a gradual decrease in the bulk resistance of the EIS device, as the RTA temperature was increased.
An integrative piRNA analysis of mouse gametes and zygotes reveals new potential origins and gene regulatory roles
Authors: Larriba Eduardo , del Mazo Jesús
Published: August 2018

Piwi-interacting RNAs (piRNAs) are a subclass of the small non-coding RNAs (sncRNAs). Their main reported function was to exert control over transposable elements (TEs) in mammalian germline. In this study undertaking a deeper bioinformatics analysis of piRNAs present in mouse oocytes, sperm cells and zygotes, we first elaborated a new piRNA database based on sequences identified as piRNAs by immunoprecipitation with PIWI proteins. Our bioinformatics analysis revealed that, at least in gametes and zygotes, piRNAs could encompass multifunctional cell-dependent regulatory molecules. Indeed, genome analysis of the piRNA mapping density (reads/kb) evidenced in all samples an enrichment of intron-derived piRNAs. Further, piRNA population was classified into sequences not associated to TEs or repeats (NRapiRNAs) and associated to repetitive genome elements (RapiRNAs). In oocytes most of the NRapiRNAs mapped to the 5′UTRs of coding mRNAs, while higher proportion of NRapiRNAs was detected in sperm cells associated to the 3′UTRs of mRNAs. This piRNA complementarity to mRNA UTRs suggests key post-transcriptional regulatory roles over mRNAs such as those encoding MHC genes. In addition, a striking association of RapiRNA with long non-coding RNAs (lncRNAs) was identified. piRNAs associated with relevant lncRNAs such as: Rab26os and GAS5 and key mRNAs, were particularly assessed.
Analyses of ovarian activity reveal repeated evolution of post-reproductive lifespans in toothed whales
Authors: Ellis Samuel , Franks Daniel W. , Nattrass Stuart , Currie Thomas E. , Cant Michael A. , Giles Deborah , Balcomb Kenneth C. , Croft Darren P.
Published: August 2018

In most species the reproductive system ages at the same rate as somatic tissue and individuals continue reproducing until death. However, females of three species – humans, killer whales and short-finned pilot whales – have been shown to display a markedly increased rate of reproductive senescence relative to somatic ageing. In these species, a significant proportion of females live beyond their reproductive lifespan: they have a post-reproductive lifespan. Research into this puzzling life-history strategy is hindered by the difficulties of quantifying the rate of reproductive senescence in wild populations. Here we present a method for measuring the relative rate of reproductive senescence in toothed whales using published physiological data. Of the sixteen species for which data are available (which does not include killer whales), we find that three have a significant post-reproductive lifespan: short-finned pilot whales, beluga whales and narwhals. Phylogenetic reconstruction suggests that female post-reproductive lifespans have evolved several times independently in toothed whales. Our study is the first evidence of a significant post-reproductive lifespan in beluga whales and narwhals which, when taken together with the evidence for post-reproductive lifespan in killer whales, doubles the number of non-human mammals known to exhibit post-reproductive lifespans in the wild.