bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent perspectives on the role of nutraceuticals as cholesterol-lowering agents
Authors: Ward Natalie , Sahebkar Amirhossein , Banach Maciej , Watts Gerald
Published: August 2017

Purpose of review

Reduction in circulating cholesterol is an important step in lowering cardiovascular risk. Although statins are the most frequently prescribed cholesterol-lowering medication, there remains a significant portion of patients who require alternative treatment options. Nutraceuticals are increasingly popular as cholesterol-lowering agents. Despite the lack of long-term trials evaluating their use on cardiovascular endpoints and mortality, several studies have demonstrated their potential cholesterol-lowering effects. The purpose of this review is to provide an update on the role of nutraceuticals as cholesterol-lowering agents. The present review will focus on individual nutraceutical compounds, which have shown modest cholesterol-lowering abilities, as well as combination nutraceuticals, which may offer potential additive and/or synergistic effects.

Recent findings

Berberine, red yeast rice, and plant sterols have moderate potential as cholesterol-lowering agents. Combination nutraceuticals, including the proprietary formulation, Armolipid Plus, appear to confer additional benefit on plasma lipid profiles, even when taken with statins and other agents.

Although robust, long-term clinical trials to examine the effects of nutraceuticals on clinical outcomes are still required, their cholesterol-lowering ability, together with their reported tolerance and safety, offer a pragmatic option for lowering plasma cholesterol levels.
Button battery ingestion in children
Authors: Eliason Michael J. , Ricca Robert L. , Gallagher Thomas Q.
Published: August 2017

Purpose of review

As the demand for small electronics continues to grow so does the risk of oesophageal ingestion of button batteries. These small but powerful sources of energy are ubiquitous in every household and when swallowed, especially in small children, have been shown to create significant injury in a short amount of time leading to long-term morbidity and possible death. This review highlights the latest findings regarding epidemiology, pathophysiology, diagnosis and management of ingested button batteries.

Recent findings

Updated epidemiology from the National Capital Poison Center, new bench research looking at injury patterns and possible mitigation strategies, updated ideas on management algorithms including the use of a trauma protocol, close-look second endoscopy and management of button batteries in the lower gastrointestinal tract are reviewed in this paper.

Despite advances in the understanding of injury mechanics and innovations leading to early diagnosis and improved management of button battery ingestion, parental and provider education remain the most important tools to keep children well tolerated from the sequelae of these potentially fatal events. Collaboration between healthcare experts, public health and industry is essential to find a safe answer to this ongoing threat.
Quality of Life Among Parents of Adolescent and Young Adult Brain Tumor Survivors
Authors: Buchbinder David K. , Fortier Michelle A. , Osann Kathryn , Wilford Justin , Shen Violet , Torno Lilibeth , Sender Leonard S. , Parsons Susan K. , Wenzel Lari
Published: August 2017

We aimed to describe the quality of life (QOL) among parents of adolescent and young adult brain tumor survivors as well as parent, survivor, and diagnosis/treatment-related factors associated with adverse QOL. A cross-sectional study of 28 parents of adolescent and young adult brain tumor survivors (who were on average 10 y postdiagnosis) was used to assess QOL. Parent QOL was measured using the Patient-Reported Outcomes Measurement Information System Global Health measure. Factors associated with adverse parent QOL were explored using logistic regression including: parent, survivor, and diagnosis/treatment-related factors. Parent QOL was within the normal range; however, 40% scored below the clinical threshold of 0.5 SD below the mean for physical and mental health. Parent perceptions of greater family impact, survivor emotional/behavioral health problems, improved cognitive function, and recurrence were associated with adverse parent physical health. Parent anger/sorrow, uncertainty, survivor emotional/behavioral health problems, speech/language problems, and recurrence were associated with adverse parent mental health. Parental emotional resources and perceptions of improved survivor peer relationships were associated with greater parent physical and mental health. The impact of a brain tumor diagnosis and treatment on the QOL of parents may be significant. Interventions are needed to ensure that the needs of parents are met.
Successful Reduced Intensity Conditioning Alternate Donor Stem Cell Transplant for Wiskott-Aldrich Syndrome
Authors: Thakkar Dhwanee , Katewa Satyendra , Rastogi Neha , Kohli Shruti , Nivargi Sagar , Yadav Satya P.
Published: August 2017

There are very few reports of reduced intensity conditioning (RIC) hematopoietic stem cell transplant (HSCT) with alternate donor for Wiskott-Aldrich syndrome (WAS) and there is no report of RIC with posttransplant cyclophosphamide (PTCy) in WAS. There is only 1 report of T cell receptor αβ and CD19-depleted haploidentical HSCT for WAS. Here we report successful outcome in 3 children with WAS who underwent successful RIC alternate donor HSCT of whom 2 (matched unrelated donor and T-cell replete haploidentical) received PTCy and 1 underwent T cell receptor αβ and CD19-depleted haploidentical HSCT. We modified conditioning used by Luznik for haploidentical HSCT by adding thiotepa 8 mg/kg and Campath or rabbit antithymoglobulin for 2 cases who received PTCy. In third case we gave fludarabine, thiotepa, and treosulfan-based conditioning. The mean duration of follow-up for these patients was 23.6 months posttransplant (range, 21 to 26 mo). All 3 patients are transfusion independent. Acute graft versus host disease (GVHD) grade I occurred in 1 and none had chronic GVHD. Chimerism of all 3 was fully donor (>95% donor) at D+30 and D+100 posttransplant. All are alive, healthy, and doing well. Our 3 cases highlight that with newer conditioning and GVHD prophylaxis approach alternate donor HSCT in WAS can become a safe and effective treatment option.
The Case for Bringing the Licensed Practical Nurse Back to the Hospital
Authors: Garner Catherine H. , Boese Suzanne M.
Published: August 2017

The expansion of the aging population, residential care facilities, and projected registered nurse shortages pose significant challenges to nurse staffing ratios. The licensed practical/vocational nursing role is now being reexamined, as acute care and long-term care facilities look at staffing models and patient safety. There is now a demand for an increase in the numbers of practical nurse education programs, which have been overlooked as a pipeline for professional nursing. Recruiting and educating practical nurses open a pathway for greater diversity in the nursing profession as well as improving patient health outcomes.
Virtually Integrated Care
Authors: Denney Shannon , Evans Elizabeth Miller
Published: August 2017

Current trends, including an aging population; the impact of the Affordable Care Act; increased complexity and acuity of patient needs; shorter hospital stays; and higher patient expectations have resulted in a significant demand for reconfiguration of the bedside nursing model. The health care system is further complicated by a shortage of highly trained nurses, challenging financial incentive models, and inefficient traditional staffing models. These challenges have increased the urgency for designing a more efficient, cost-effective care delivery model. One large national system is redefining how it cares for patients in the acute care setting in preparation for the Next Era. Catholic Health Initiatives is developing a new integrated model of care that combines advances in technology with a restructuring of nursing roles for significantly more efficient and effective care. The model is person-centered and allows team members to practice to the full extent of their education and training. The model emphasizes care from the right skill level, for the right patient need, at the right time. This article begins to describe the planning and implementation of the Virtually Integrated Care Team (VIC) pilot project on 2 medical-surgical units within the Catholic Health Initiatives system.
Applying Bureaucratic Caring Theory and the Chronic Care Model to Improve Staff and Patient Self-Efficacy
Authors: Potter Marcia A. , Wilson Candy
Published: August 2017

Patient activation and engagement can be powerful enablers for health outcomes that are just as important as staff engagement and satisfaction. The authors applied the Bureaucratic Caring Theory and the Chronic Care Model to a process improvement project designed to link activation, engagement, satisfaction, and health outcomes. Twenty-two adults with diabetes and 7 staff members caring for them participated in a 12-week process improvement project that incorporated a time-based element of longitudinal care with skill-based competencies to provide collaborative, team-based care to patients with type 2 diabetes. Patients completed satisfaction surveys at the end of their clinical encounters. Staff members completed satisfaction surveys pre- and postimplementation. The authors analyzed hemoglobin A1C levels pre- and postimplementation. As engagement and activation increased for both staff and patients, hemoglobin A1C levels decreased. The clinical implication is that the use of Bureaucratic Caring Theory may foster caring while broad application of the Chronic Care Model may improve self-efficacy, create healthier populations, and reduce health care costs.
Impact of Interactive Video Communication Versus Text-Based Feedback on Teaching, Social, and Cognitive Presence in Online Learning Communities
Authors: Seckman Charlotte
Published: August 2017

A key element to online learning is the ability to create a sense of presence to improve learning outcomes. This quasi-experimental study evaluated the impact of interactive video communication versus text-based feedback and found a significant difference between the 2 groups related to teaching, social, and cognitive presence. Recommendations to enhance presence should focus on providing timely feedback, interactive learning experiences, and opportunities for students to establish relationships with peers and faculty.
Is There a Mismatch Between the Perspectives of Patients and Regulators on Healthcare Quality? A Survey Study
Authors: Bouwman Renée , Bomhoff Manja , Robben Paul , Friele Roland
Published: August 2017

Objectives

Internationally, healthcare quality regulators are criticized for failing to respond to patients’ complaints. Patient involvement is, therefore, an important item on the policy agenda. However, it can be argued that there is a discrepancy between the patients’ perspective and current regulatory approaches.

This study examines whether a discrepancy exists between the perspectives of patients and regulators on healthcare quality.

Methods

A questionnaire was sent to 996 people who had registered a complaint with the Dutch Healthcare Inspectorate to measure expectations of and experiences with the Inspectorate. A taxonomy was used to classify their complaints into the clinical, relationship, or management domains.

Results

The response was 54%. More complaints about clinical issues (56%, P = 0.000) were investigated by the regulator than complaints about organizational (37%) and relational issues (51%). Patients with complaints about management issues less often indicated (13%, P = 0.002) that healthcare is improved by making their complaint than patients with complaints about clinical or relationship issues did (22%–23%). Patients who reported about relational issues with care providers attached more importance to issuing sanctions against the care provider than other patients (mean score 2.89 versus 2.62–2.68, P = 0.006).

Conclusions

The predominant clinical approach taken by regulators does not match the patients’ perspective of what is relevant for healthcare quality. In addition, patients seem to be more tolerant of what they perceive to be clinical or management errors than of perceived relational deficiencies in care providers. If regulators want to give patients a voice, they should expand their horizon beyond the medical framework.
Prescribing Errors With Low-Molecular-Weight Heparins
Authors: Slikkerveer Marielle , van de Plas Afke , Driessen Johanna H.M. , Wijngaard Robin , de Vries Frank , Olie Renske , Meertens Nathalie , van den Bemt Patricia
Published: August 2017

Background

Low–molecular-weight heparins (LMWHs) are used in the prevention and treatment of venous thromboembolism (VTE). Bleeding is the primary major complication of LMWH therapy, which is associated with dose. The administration of appropriate dosages of LMWHs depends on the patient’s risk of VTE, risk of bleeding, bodyweight, and renal function. Therefore, LMWH prescribing is prone to errors. However, no earlier study has explored the frequency of prescribing errors with LMWH.

Purpose

The aim of the study was to determine the frequency and determinants of in-hospital LMWH-prescribing errors.

Methods

A cross-sectional study was conducted to examine the frequency and determinants of LMWH prescribing errors between April and August 2014. We randomly selected 500 patients 18 years and older with at least one LMWH prescription during inpatient hospitalization. A prescribing error was a deviation from the internal hospital guidelines. Logistic regression estimated determinants of prescribing error.

Results

A prescribing error was present with 34% of all LMWH users. The most frequently recorded error was a dose that was not adjusted to body weight and/or renal function (85%). Prophylactic LMWH prescribing in medical wards was associated with a higher risk of prescribing error as compared with surgical wards.

Conclusions

The frequency of prescribing errors was 34% in a tertiary care hospital. Being a patient with prophylactic LMWH use on a medical ward is a determinant for LMWH prescribing error. Interventions that will lead to better electronic recording of body weight and more awareness among medical doctors may reduce the total number of prescribing errors.
miRNA-214 Protects Sepsis-Induced Myocardial Injury
Authors: Ge Chen , Liu Junhang , Dong Shimin
Published: August 2017

Sepsis can cause myocardial injury, which is one of the leading causes of death in critically ill patients. The underlying mechanisms associated with sepsis-induced myocardial injury (SIMI) include impaired cardiac contractility, excessive cardiac inflammation, oxidative stress, cardiomyocyte apoptosis, and so on. SIMI is usually accompanied with dynamic changes of microRNAs (miRNAs) expression. And previous studies have shown that miR-214 plays a vital role in the protection of cardiomyocyte subjected to oxidative stress. In this study, we aimed to test whether miRNA-214 plays any roles in sepsis-induced myocardial injury. We performed quantitative real-time polymerase chain reaction in the septic mouse model induced by cecal ligation and puncture (CLP) and found the expression of miR-214 was upregulated. Then we transfected with the miRNA-214 precursor (pre-miR-214) to upregulate miR-214 expression and with the miR-214 inhibitor (anti-miR-214) to downregulate miR-214 expression respectively. Pre-miR-214 mouse model, anti-miR-214 mouse model, and wild-type mice were subjected to CLP or sham surgery. We observed that compared with control wild types, cardiac function, inflammatory response, the degree of myocardial injury, and myocyte apoptosis were remarkably alleviated in CLP-treated pre-miR-214 mice and aggravated in CLP-treated anti-miR-214 mice. Taken together, our study reveals that miR-214 has a protective effect in SIMI and thereby may provide a potential novel approach to treat SIMI.
Responses of neurogenesis and neuroplasticity related genes to elevated CO
2
levels in the brain of three teleost species
Authors: Lai Floriana , Fagernes Cathrine E. , Bernier Nicholas J. , Miller Gabrielle M. , Munday Philip L. , Jutfelt Fredrik , Nilsson Göran E.
Published: August 2017

The continuous increase of anthropogenic CO
2
in the atmosphere resulting in ocean acidification has been reported to affect brain function in some fishes. During adulthood, cell proliferation is fundamental for fish brain growth and for it to adapt in response to external stimuli, such as environmental changes. Here we report the first expression study of genes regulating neurogenesis and neuroplasticity in brains of three-spined stickleback (
Gasterosteus aculeatus
), cinnamon anemonefish (
Amphiprion melanopus
) and spiny damselfish (
Acanthochromis polyacanthus
) exposed to elevated CO
2
. The mRNA expression levels of the neurogenic differentiation factor (NeuroD) and doublecortin (DCX) were upregulated in three-spined stickleback exposed to high-CO
2
compared with controls, while no changes were detected in the other species. The mRNA expression levels of the proliferating cell nuclear antigen (PCNA) and the brain-derived neurotrophic factor (BDNF) remained unaffected in the high-CO
2
exposed groups compared to the control in all three species. These results indicate a species-specific regulation of genes involved in neurogenesis in response to elevated ambient CO
2
levels. The higher expression of NeuroD and DCX mRNA transcripts in the brain of high-CO
2
–exposed three-spined stickleback, together with the lack of effects on mRNA levels in cinnamon anemonefish and spiny damselfish, indicate differences in coping mechanisms among fish in response to the predicted-future CO
2
level.
Ernest Armstrong McCulloch. 21 April 1926—20 January 2011
Authors: Mak Tak Wah
Published: August 2017

Ernest Armstrong McCulloch was half of the brilliant partnership that discovered haematopoietic stem cells (HSCs) and changed how we think about human tissue generation and regeneration. Based at the Ontario Cancer Institute (now the Princess Margaret Cancer Centre) in Toronto, the haematologist ‘Bun’ McCulloch, together with James E. Till, a physicist with a steel-trap mind, exercised their penchant for adventurous ‘big picture’ thinking in devising experiments to identify stem cells. This exceptional team was the first to demonstrate that HSCs have the dual capacity to self-renew and to differentiate into a vast array of mature haematopoietic cells. Their trainees, as well as investigators elsewhere, built on McCulloch and Till's findings not only to isolate and characterize HSCs and progenitors derived from them, but also to devise therapies for certain blood disorders. Later in his career, Ernest focused on characterizing the malignant cells of human leukaemias and determining the effects of various drugs on leukaemic cell growth. The implications of Till and McCulloch's work continue to be profound and underpin many significant breakthroughs in our knowledge of normal cellular physiology, pathophysiology, tumorigenesis and tissue transplantation. Indeed, regenerative medicine owes its very existence to the stem cell discoveries of McCulloch, Till and others. At times eccentric and demanding, but always well spoken, incisive and erudite, Ernest personified the outstanding research scientist cloaked in Canadian modesty. His legacy lives on in the bright therapeutic future emerging from the rigorous stem cell research being conducted in Canada and around the world.
Finite cell-size effects on protein variability in Turing patterned tissues
Authors: Buceta Javier
Published: August 2017

Herein we present a framework to characterize different sources of protein expression variability in Turing patterned tissues. In this context, we introduce the concept of granular noise to account for the unavoidable fluctuations due to finite cell-size effects and show that the nearest-neighbours autocorrelation function provides the means to measure it. To test our findings, we performin silicoexperiments of growing tissues driven by a generic activator–inhibitor dynamics. Our results show that the relative importance of different sources of noise depends on the ratio between the characteristic size of cells and that of the pattern domains and on the ratio between the pattern amplitude and the effective intensity of the biochemical fluctuations. Importantly, our framework provides the tools to measure and distinguish different stochastic contributions during patterning: granularity versus biochemical noise. In addition, our analysis identifies the protein species that buffer the stochasticity the best and, consequently, it can help to determine key instructive signals in systems driven by a Turing instability. Altogether, we expect our study to be relevant in developmental processes leading to the formation of periodic patterns in tissues.
Human movement, cooperation and the effectiveness of coordinated vector control strategies
Authors: Stone Chris M. , Schwab Samantha R. , Fonseca Dina M. , Fefferman Nina H.
Published: August 2017

Vector-borne disease transmission is often typified by highly focal transmission and influenced by movement of hosts and vectors across different scales. The ecological and environmental conditions (including those created by humans through vector control programmes) that result in metapopulation dynamics remain poorly understood. The development of control strategies that would most effectively limit outbreaks given such dynamics is particularly urgent given the recent epidemics of dengue, chikungunya and Zika viruses. We developed a stochastic, spatial model of vector-borne disease transmission, allowing for movement of hosts between patches. Our model is applicable to arbovirus transmission by
Aedes aegypti
in urban settings and was parametrized to capture Zika virus transmission in particular. Using simulations, we investigated the extent to which two aspects of vector control strategies are affected by human commuting patterns: the extent of coordination and cooperation between neighbouring communities. We find that transmission intensity is highest at intermediate levels of host movement. The extent to which coordination of control activities among neighbouring patches decreases the prevalence of infection is affected by both how frequently humans commute and the proportion of neighbouring patches that commits to vector surveillance and control activities. At high levels of host movement, patches that do not contribute to vector control may act as sources of infection in the landscape, yet have comparable levels of prevalence as patches that do cooperate. This result suggests that real cooperation among neighbours will be critical to the development of effective pro-active strategies for vector-borne disease control in today's commuter-linked communities.
A biophysical approach to daunorubicin interaction with model membranes: relevance for the drug's biological activity
Authors: Alves Ana Catarina , Ribeiro Daniela , Horta Miguel , Lima José L. F. C. , Nunes Cláudia , Reis Salette
Published: August 2017

Daunorubicin is extensively used in chemotherapy for diverse types of cancer. Over the years, evidence has suggested that the mechanisms by which daunorubicin causes cytotoxic effects are also associated with interactions at the membrane level. The aim of the present work was to study the interplay between daunorubicin and mimetic membrane models composed of different ratios of 1,2-dimyristoyl-
sn
-glycero-
3
-phosphocholine (DMPC), sphingomyelin (SM) and cholesterol (Chol). Several biophysical parameters were assessed using liposomes as mimetic model membranes. Thereby, the ability of daunorubicin to partition into lipid bilayers, its apparent location within the membrane and its effect on membrane fluidity were investigated. The results showed that daunorubicin has higher affinity for lipid bilayers composed of DMPC, followed by DMPC : SM, DMPC : Chol and lastly by DMPC : SM : Chol. The addition of SM or Chol into DMPC membranes not only increases the complexity of the model membrane but also decreases its fluidity, which, in turn, reduces the amount of anticancer drug that can partition into these mimetic models. Fluorescence quenching studies suggest a broad distribution of the drug across the bilayer thickness, with a preferential location in the phospholipid tails. The gathered data support that daunorubicin permeates all types of membranes to different degrees, interacts with phospholipids through electrostatic and hydrophobic bonds and causes alterations in the biophysical properties of the bilayers, namely in membrane fluidity. In fact, a decrease in membrane fluidity can be observed in the acyl region of the phospholipids. Ultimately, such outcomes can be correlated with daunorubicin's biological action, where membrane structure and lipid composition have an important role. In fact, the results indicate that the intercalation of daunorubicin between the phospholipids can also take place in rigid domains, such as rafts that are known to be involved in different receptor processes, which are important for cellular function.
FGFR3–TACC3 cancer gene fusions cause mitotic defects by removal of endogenous TACC3 from the mitotic spindle
Authors: Sarkar Sourav , Ryan Ellis L. , Royle Stephen J.
Published: August 2017

Fibroblast growth factor receptor 3–transforming acidic coiled-coil containing protein 3 (FGFR3–TACC3; FT3) is a gene fusion resulting from rearrangement of chromosome 4 that has been identified in many cancers including those of the urinary bladder. Altered FGFR3 signalling in FT3-positive cells is thought to contribute to cancer progression. However, potential changes in TACC3 function in these cells have not been explored. TACC3 is a mitotic spindle protein required for accurate chromosome segregation. Errors in segregation lead to aneuploidy, which can contribute to cancer progression. Here we show that FT3-positive bladder cancer cells have lower levels of endogenous TACC3 on the mitotic spindle, and that this is sufficient to cause mitotic defects. FT3 is not localized to the mitotic spindle, and by virtue of its TACC domain, recruits endogenous TACC3 away from the spindle. Knockdown of the fusion gene or low-level overexpression of TACC3 partially rescues the chromosome segregation defects in FT3-positive bladder cancer cells. This function of FT3 is specific to TACC3 as inhibition of FGFR3 signalling does not rescue the TACC3 level on the spindle in these cancer cells. Models of FT3-mediated carcinogenesis should, therefore, include altered mitotic functions of TACC3 as well as altered FGFR3 signalling.
Differential metal-binding properties of dynamic acylhydrazone polymers and their sensing applications
Authors: Gao Siheng , Li Lijie , Vohra Ismail , Zha Daijun , You Lei
Published: August 2017

As one of common dynamic covalent bonds, acylhydrazone bond plays an important role in developing intelligent responsive materials. In this report, we present acylhydrazone-based dynamic polymers with multi-stimuli responsiveness, particularly metal recognition behaviours and their modulation. A series of polyacylhydrazones with different metal-binding sites were designed and prepared in a modular fashion. Titration of these receptors with a diverse set of metal ions, including Cu
2+
, Zn
2+
and La
3+
, resulted in unique optical changes, and both the sensitivity and selectivity profiles can be regulated. Moreover, the metal-binding feature was facilely modulated by changing the solvent. The addition of weakly basic anions was employed to further fine-tune the responsiveness of the polymers by taking advantage of the cooperative effect with metal coordination. Finally, the sensitive detection of 6-mercaptopurine and pyrophosphate was achieved to demonstrate the application potential of these systems.
Recursive modular modelling methodology for lumped-parameter dynamic systems
Authors: Orsino Renato Maia Matarazzo
Published: August 2017

This paper proposes a novel approach to the modelling of lumped-parameter dynamic systems, based on representing them by hierarchies of mathematical models of increasing complexity instead of a single (complex) model. Exploring the multilevel modularity that these systems typically exhibit, a general recursive modelling methodology is proposed, in order to conciliate the use of the already existing modelling techniques. The general algorithm is based on a fundamental theorem that states the conditions for computing projection operators recursively. Three procedures for these computations are discussed: orthonormalization, use of orthogonal complements and use of generalized inverses. The novel methodology is also applied for the development of a recursive algorithm based on the Udwadia–Kalaba equation, which proves to be identical to the one of a Kalman filter for estimating the state of a static process, given a sequence of noiseless measurements representing the constraints that must be satisfied by the system.
Organic molecule fluorescence as an experimental test-bed for quantum jumps in thermodynamics
Authors: Browne Cormac , Farrow Tristan , Dahlsten Oscar C. O. , Taylor Robert A. , Vlatko Vedral
Published: August 2017

We demonstrate with an experiment how molecules are a natural test bed for probing fundamental quantum thermodynamics. Single-molecule spectroscopy has undergone transformative change in the past decade with the advent of techniques permitting individual molecules to be distinguished and probed. We demonstrate that the quantum Jarzynski equality for heat is satisfied in this set-up by considering the time-resolved emission spectrum of organic molecules as arising from quantum jumps between states. This relates the heat dissipated into the environment to the free energy difference between the initial and final state. We demonstrate also how utilizing the quantum Jarzynski equality allows for the detection of energy shifts within a molecule, beyond the relative shift.
Numerical simulations of drumlin formation
Authors: Fannon J. S. , Fowler A. C. , Moyles I. R.
Published: August 2017

We summarize the present form of the instability theory for drumlin formation, which describes the coupled subglacial flow of ice, water and sediment. This model has evolved over the last 20 years, and is now at the point where it can predict instabilities corresponding to ribbed moraine, drumlins and mega-scale glacial lineations, but efforts to provide numerical solutions of the model have been limited. The present summary adds some slight nuances to previously published versions of the theory, notably concerning the constitutive description of the subglacial water film and its flow. A new numerical method is devised to solve the model, and we show that it can be solved for realistic values of most of the parameters, with the exception of that corresponding to the water film thickness. We show that evolved bedforms can be three-dimensional and of the correct sizes, and we explore to some extent the variation of the solutions with the model’s parameters.
What difference does a century make? Shifts in the ecosystem structure of the Ross Sea, Antarctica, as evidenced from a sentinel species, the Weddell seal
Authors: Hückstädt Luis A. , McCarthy Matthew D. , Koch Paul L. , Costa Daniel P.
Published: August 2017

The arrival of humans to Antarctica's Ross Sea (100+ years ago) led to a slow, but sustained increase in human activities in the area. To investigate if human presence has influenced the structure of the ecosystem over the last century, we compared historical (
ca
100 years old) and modern samples of a sentinel species, the Weddell seal (
Leptonychotes weddellii
), using both bulk tissue and compound-specific stable isotope analysis. The historical isotopic niche of Weddell seals was over five times larger than the modern niche. The isotopic values of individual amino acids showed a clear segregation between historical and modern samples, indicative of differences at the base of the trophic web. Further, we found no significant differences in the trophic position of Weddell seals between the two periods. Our study revealed that the Ross Sea has undergone detectable changes (i.e. in the primary producers community) in the last century, but the presence of humans has not disrupted trophic interactions supporting Weddell seals.
The four-flipper swimming method of plesiosaurs enabled efficient and effective locomotion
Authors: Muscutt Luke E. , Dyke Gareth , Weymouth Gabriel D. , Naish Darren , Palmer Colin , Ganapathisubramani Bharathram
Published: August 2017

The extinct ocean-going plesiosaurs were unique within vertebrates because they used two flipper pairs identical in morphology for propulsion. Although fossils of these Mesozoic marine reptiles have been known for more than two centuries, the function and dynamics of their tandem-flipper propulsion system has always been unclear and controversial. We address this question quantitatively for the first time in this study, reporting a series of precisely controlled water tank experiments that use reconstructed plesiosaur flippers scaled from well-preserved fossils. Our aim was to determine which limb movements would have resulted in the most efficient and effective propulsion. We show that plesiosaur hind flippers generated up to 60% more thrust and 40% higher efficiency when operating in harmony with their forward counterparts, when compared with operating alone, and the spacing and relative motion between the flippers was critical in governing these increases. The results of our analyses show that this phenomenon was probably present across the whole range of plesiosaur flipper motion and resolves the centuries-old debate about the propulsion style of these marine reptiles, as well as indicating why they retained two pairs of flippers for more than 100 million years.
How predation shapes the social interaction rules of shoaling fish
Authors: Herbert-Read James E. , Rosén Emil , Szorkovszky Alex , Ioannou Christos C. , Rogell Björn , Perna Andrea , Ramnarine Indar W. , Kotrschal Alexander , Kolm Niclas , Krause Jens , Sumpter David J. T.
Published: August 2017

Predation is thought to shape the macroscopic properties of animal groups, making moving groups more cohesive and coordinated. Precisely how predation has shaped individuals' fine-scale social interactions in natural populations, however, is unknown. Using high-resolution tracking data of shoaling fish (Poecilia reticulata) from populations differing in natural predation pressure, we show how predation adapts individuals' social interaction rules. Fish originating from high predation environments formed larger, more cohesive, but not more polarized groups than fish from low predation environments. Using a new approach to detect the discrete points in time when individuals decide to update their movements based on the available social cues, we determine how these collective properties emerge from individuals' microscopic social interactions. We first confirm predictions that predation shapes the attraction–repulsion dynamic of these fish, reducing the critical distance at which neighbours move apart, or come back together. While we find strong evidence that fish align with their near neighbours, we do not find that predation shapes the strength or likelihood of these alignment tendencies. We also find that predation sharpens individuals' acceleration and deceleration responses, implying key perceptual and energetic differences associated with how individuals move in different predation regimes. Our results reveal how predation can shape the social interactions of individuals in groups, ultimately driving differences in groups' collective behaviour.
Coevolution in the timing of GABAergic and pyramidal neuron maturation in primates
Authors: Charvet Christine J. , Šimić Goran , Kostović Ivica , Knezović Vinka , Vukšić Mario , Babić Leko Mirjana , Takahashi Emi , Sherwood Chet C. , Wolfe Marnin D. , Finlay Barbara L.
Published: August 2017

The cortex of primates is relatively expanded compared with many other mammals, yet little is known about what developmental processes account for the expansion of cortical subtype numbers in primates, including humans. We asked whether GABAergic and pyramidal neuron production occurs for longer than expected in primates than in mice in a sample of 86 developing primate and rodent brains. We use high-resolution structural, diffusion MR scans and histological material to compare the timing of the ganglionic eminences (GE) and cortical proliferative pool (CPP) maturation between humans, macaques, rats, and mice. We also compare the timing of post-neurogenetic maturation of GABAergic and pyramidal neurons in primates (i.e. humans, macaques) relative to rats and mice to identify whether delays in neurogenesis are concomitant with delayed post-neurogenetic maturation. We found that the growth of the GE and CPP are both selectively delayed compared with other events in primates. By contrast, the timing of post-neurogenetic GABAergic and pyramidal events (e.g. synaptogenesis) are predictable from the timing of other events in primates and in studied rodents. The extended duration of GABAergic and pyramidal neuron production is associated with the amplification of GABAerigc and pyramidal neuron numbers in the human and non-human primate cortex.
A rare missense mutation inMYH6confers high risk of coarctation of the aorta
Authors: Bjornsson Thorsteinn , Thorolfsdottir Rosa B. , Sveinbjornsson Gardar , Sulem Patrick , Norddahl Gudmundur L. , Helgadottir Anna , Gretarsdottir Solveig , Magnusdottir Audur , Danielsen Ragnar , Sigurdsson Emil L. , Adalsteinsdottir Berglind , Gunnarsson Sverrir I. , Jonsdottir Ingileif , Arnar David O. , Helgason Hrodmar , Gudbjartsson Tomas , Gudbjartsson Daniel F. , Thorsteinsdottir Unnur , Holm Hilma , Stefansson Kari
Published: August 2017

Coarctation of the aorta (CoA) accounts for 4-8% of congenital heart defects (CHDs) and carries substantial morbidity despite treatment1. We performed a genome-wide association study (GWAS) of CoA among 120 Icelandic cases and 355,166 controls and found association with a rare (frequency = 0.34%) missense mutation p.Arg721Trp inMYH6(odds ratio (OR) = 44.2,P= 5.0x10-22), encoding an essential sarcomere protein. Approximately 20% of CoA cases in Iceland carry p.Arg721Trp. This is the first mutation associated with non-familial or sporadic CoA at a population level. P.Arg721Trp also associates with risk of bicuspid aortic valve (BAV) and other CHDs and has been reported to have a broad effect on cardiac electrical function and to associate strongly with sick sinus syndrome (SSS) and atrial fibrillation (AF)2. These findings suggest that p.Arg721Trp inMYH6causes a cardiac syndrome with highly variable expressivity, and emphasize the major importance of sarcomere integrity for cardiac development and function.
Dominance of ST131Escherichia colicarryingblaCTX-Min patients with bloodstream infections caused by cephalosporin-resistant strains in Australia, New Zealand and Singapore: whole genome analysis of isolates from a randomised trial
Authors: Harris Patrick N. A. , Ben Zakour Nouri L. , Roberts Leah W. , Wailan Alexander M. , Zowawi Hosam M. , Tambyah Paul A. , Lye David C. , Jureen Roland , Lee Tau H. , Yin Mo , Izharuddin Ezlyn , Looke David , Runnegar Naomi , Rogers Benjamin , Bhally Hasan , Crowe Amy , Schembri Mark A. , Beatson Scott , Paterson David L. ,   on behalf of the MERINO Trial investigators
Published: August 2017

Synopsis/Abstract

Objectives

To characterise multi-drug resistantEscherichia coliisolated from patients in Australia, New Zealand and Singapore with bloodstream infection (BSI).

Methods

We prospectively collected third-generation cephalosporin resistant (3GC-R)E. colifrom blood cultures obtained from patients enrolled in a randomised controlled trial. Whole genome sequencing was used to characterise antibiotic resistance genes, sequence types (STs), plasmids and phylogenetic relationships. Antibiotic susceptibility was determined using disk diffusion and Etest.

Results

A total of 70E. coliwere included, of which the majority were ST131 (61.4%). BSI was most frequently from a urinary source (69.6%), community-associated (62.9%) and in older patients (median age 71 years [IQR 64-81]). The median Pitt bacteraemia score at presentation was 1 (IQR 0-2, range 0-3) and ICU admission was infrequent (3.1%). ST131 possessed significantly more acquired resistance genes than non-ST131 (p=0.003). Clade C1/C2 ST131 predominated (30.2% and 53.5% of all ST131 respectively) and these were all resistant to ciprofloxacin. All clade A ST131 were community-associated. The predominant ESBL types wereblaCTX-M(78.6% of isolates) and were strongly associated with ST131, with the majorityblaCTX-M-15. Clade C1 was associated withblaCTX-M-14andblaCTX-M-27, whereasblaCTX-M-15predominated in clade C2. Plasmid-mediated AmpC (p-AmpC) genes (mainlyblaCMY-2) were also frequent (17.1%) but were more common with non-ST131 strains (p< 0.001). The majority of plasmid replicon types were IncF.

Conclusions

In a prospective collection of 3GC-RE. colicausing BSI in the Australasian region, community-associated Clade C1/C2 ST131 predominate in association withblaCTX-MESBLs, although a significant proportion of non-ST131 strains carriedblaCMY-2.
Fishing for New Bt Receptors in Diamondback Moth
Authors: Chen Yazhou , Huang Yuping , Liu Qun , Xu Jun , Hogenhout Saskia , Huang Yongping , Tan Anjiang
Published: August 2017

Bt toxins bind to receptors in the brush border membrane of the insect gut and create pores, leading to insect death. Bt-resistant insects demonstrate reduced binding of the Bt toxins to gut membranes. However, our understanding of the gut receptors involved in Bt toxin binding, and which receptors confer resistance to these toxins is incomplete, especially in diamondback moth (Plutella xylostella), a major agricultural pest. Identifying receptors has remained challenging because we lack sufficiently sensitive methods to detect Bt receptor interactions. Here, we report a modified far-immunoblotting technique, which revealed a broad spectrum of binding targets for the Bt toxins Cry1Ac, Cry1Ab, and Cry1Bd in diamondback moth. We confirm the role of the glucosinolate sulfatases GSS1 and GSS2 in Cry1Bd toxicity. GSS1 and GSS2 bind directly to Cry1Bd, and their expression is crucial for Cry1Bd toxicity. These results improve our understanding of the molecular mechanisms of Bt toxicity.

AUTHOR SUMMARY

The Bt toxins, from the soil bacteriumBacillus thuringiensis, have wide applications in agriculture as insecticides applied to plants or expressed in genetically modified crops. Bt toxins bind to receptors in the brush border membrane of the insect gut and create pores leading to insect death. The success of the Bt toxins in controlling insect pests has been hindered by the emergence of resistant insects, which show reduced binding of Bt to their gut membranes. Although ongoing research has identified a few receptors, many remain unknown and the mechanisms by which these receptors cause resistance remain unclear. Here, we used a modified far-immunoblotting technique to identify proteins that bind to the toxins Cry1Ac, Cry1Ab, and Cry1Bd in the diamondback moth. This identified two glucosinolate sulfatases that bind directly to Cry1Bd; also, the toxicity of Cry1Bd requires expression of these glucosinolate sulfatases. Therefore, identification of these candidate receptors improves our understanding of Bt function and resistance.
GenomeDISCO: A concordance score for chromosome conformation capture experiments using random walks on contact map graphs
Authors: Ursu Oana , Boley Nathan , Taranova Maryna , Wang Y.X. Rachel , Yardimci Galip Gurkan , Noble William Stafford , Kundaje Anshul
Published: August 2017

Motivation

The three-dimensional organization of chromatin plays a critical role in gene regulation and disease. High-throughput chromosome conformation capture experiments such as Hi-C are used to obtain genome-wide maps of 3D chromatin contacts. However, robust estimation of data quality and systematic comparison of these contact maps is challenging due to the multi-scale, hierarchical structure of chromatin contacts and the resulting properties of experimental noise in the data. Measuring concordance of contact maps is important for assessing reproducibility of replicate experiments and for modeling variation between different cellular contexts.

Results

We introduce a concordance measure called GenomeDISCO (DIfferences between Smoothed COntact maps) for assessing the similarity of a pair of contact maps obtained from chromosome conformation capture experiments. The key idea is to smooth contact maps using random walks on the contact map graph, before estimating concordance. We use simulated datasets to benchmark GenomeDISCO’s sensitivity to different types of noise that affect chromatin contact maps. When applied to a large collection of Hi-C datasets, GenomeDISCO accurately distinguishes biological replicates from samples obtained from different cell types. GenomeDISCO also generalizes to other chromosome conformation capture assays, such as HiChIP.

Availability

Software implementing GenomeDISCO is available athttps://github.com/kundajelab/genomedisco.

Contact

akundaje@stanford.edu

Supplementary information

Supplementary data are available atBioinformaticsonline.
Identifying weak signals in inhomogeneous neuronal images for large-scale tracing of neurites
Authors: Li Shiwei , Quan Tingwei , Zhou Hang , Yin FangFang , Li Anan , Fu Ling , Luo Qingming , Gong Hui , Zeng Shaoqun
Published: August 2017

Reconstructing neuronal morphology across different regions or even the whole brain is important in many areas of neuroscience research. Large-scale tracing of neurites constitutes the core of this type of reconstruction and has many challenges. One key challenge is how to identify a weak signal from an inhomogeneous background. Here, we addressed this problem by constructing an identification model. In this model, empirical observations made from neuronal images are summarized into rules, which are used to design feature vectors that display the differences between the foreground and background, and a support vector machine is used to learn these feature vectors. We embedded this identification model into a tool that we previously developed, SparseTracer, and termed this integration SparseTracer-Learned Feature Vector (ST-LFV). ST-LFV can trace neurites with extremely weak signals (signal-to-background-noise ratio <1.1) against an inhomogeneous background. By testing 12 sub-blocks extracted from a whole imaging dataset, ST-LFV can achieve an average recall rate of 0.99 and precision rate of 0.97, which is superior to that of SparseTracer (which has an average recall rate of 0.93 and average precision rate of 0.86), indicating that this method is well suited to weak signal identification. We applied ST-LFV to trace neurites from large-scale images (approximately 105 GB). During the tracing process, obtaining results equivalent to the ground truth required only one round of manual editing for ST-LFV compared to 20 rounds of manual editing for SparseTracer. This improvement in the level of automatic reconstruction indicates that ST-LFV has the potential to rapidly reconstruct sparsely distributed neurons at the scale of an entire brain.