bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural basis for the mutual antagonism of cAMP and TRIP8b in regulating HCN channel function
Authors: Saponaro Andrea , Pauleta Sofia R. , Cantini Francesca , Matzapetakis Manolis , Hammann Christian , Donadoni Chiara , Hu Lei , Thiel Gerhard , Banci Lucia , Santoro Bina , Moroni Anna
Published: September 2014

Significance

cAMP regulation of ion channels controls higher brain functions, such as sleep, memory, and cognition. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by the direct binding of cAMP to their cytoplasmic tail and inhibited by the neuronal β-subunit tetratricopeptide repeat-containing Rab8b interacting protein (TRIP8b), which prevents cAMP binding. Understanding the molecular mechanisms of regulation of this family of ion channels is critical because it pertains to the physiological processes and diseases associated with dysfunctions in the HCN current. Here, we explain the dual regulatory system of HCN2 channels in atomic detail. cAMP and TRIP8b do not compete for the same binding site on the HCN2 cytoplasmic tail; rather, they exert their mutual competition by promoting and stabilizing two different conformational states of the protein.
Primed 3D injectable microniches enabling low-dosage cell therapy for critical limb ischemia
Authors: Li Yaqian , Liu Wei , Liu Fei , Zeng Yang , Zuo Simin , Feng Siyu , Qi Chunxiao , Wang Bingjie , Yan Xiaojun , Khademhosseini Ali , Bai Jing , Du Yanan
Published: September 2014

Significance

Optimal cell delivery strategies are in urgent need to enhance the specificity, efficacy, and reproducibility of cell therapy leading to minimized cell dosage and side effects. Here, we addressed this unmet need by developing injectable 3D microscale cellular niches (microniches) based on biocompatible and biodegradable gelatin microcryogels. Dramatic improvement in cell retention, survival, and therapeutic effects enabled by the primed 3D microniches was demonstrated in treatment of critical limb ischemia (CLI) in mouse models compared with the free cell-based therapy. To the best of our knowledge, this is the first convincing demonstration of injectable and primed cell delivery strategy realizing superior therapeutic efficacy with the lowest cell dosage for treating CLI in mouse model.
A rock engraving made by Neanderthals in Gibraltar
Authors: Rodríguez-Vidal Joaquín , d’Errico Francesco , Pacheco Francisco Giles , Blasco Ruth , Rosell Jordi , Jennings Richard P. , Queffelec Alain , Finlayson Geraldine , Fa Darren A. , Gutiérrez López José María , Carrión José S. , Negro Juan José , Finlayson Stewart , Cáceres Luís M. , Bernal Marco A. , Fernández Jiménez Santiago , Finlayson Clive
Published: September 2014

Significance

The production of purposely made painted or engraved designs on cave walls is recognized as a major cognitive step in human evolution, considered exclusive to modern humans. Here we present the first known example of an abstract pattern engraved by Neanderthals, from Gorham’s Cave in Gibraltar. It consists of a deeply impressed cross-hatching carved into the bedrock of the cave older than 39 cal kyr. The engraving was made before the accumulation of Mousterian layer IV. Most of the lines composing the design were made by repeatedly and carefully passing a pointed lithic tool into the grooves, excluding the possibility of an unintentional or utilitarian origin. This discovery demonstrates the Neanderthals’ capacity for abstract thought and expression.
Density-based separation in multiphase systems provides a simple method to identify sickle cell disease
Authors: Kumar Ashok A. , Patton Matthew R. , Hennek Jonathan W. , Lee Si Yi Ryan , D’Alesio-Spina Gaetana , Yang Xiaoxi , Kanter Julie , Shevkoplyas Sergey S. , Brugnara Carlo , Whitesides George M.
Published: September 2014

Significance

Red blood cells with a high density (ρ > 1.120 g/cm
3
) are characteristic of sickle cell disease. This paper demonstrates a density-based separation of red blood cells in a system of aqueous multiphase polymers that enables a visual test that identifies sickle cell disease, starting from samples of whole blood, in less than 12 min. This low-cost, simple test could provide a means to enable diagnosis of sickle cell disease in low-resource settings and enable life-saving interventions for children with the disease. The method itself provides a demonstration of the use of a biophysical indicator (here, density) rather than a biochemical marker (e.g., proteins separated by gel electrophoresis) as a means to do point-of-care hematology.
C-terminal domain small phosphatase 1 and MAP kinase reciprocally control REST stability and neuronal differentiation
Authors: Nesti Edmund , Corson Glen M. , McCleskey Maxwell , Oyer Jon A. , Mandel Gail
Published: September 2014

Significance

A fundamental process involved in nervous-system formation is the conversion of stem cells into mature neurons. A key transcription factor in this regard is repressor element 1 (RE1) silencing transcription factor (REST), which suppresses the neuronal phenotype in stem cells and must be eliminated to promote the expression of neuronal genes in postmitotic neurons. We find that a phosphatase, C-terminal domain small phosphatase 1, coexpressed with REST in stem cells, dephosphorylates a newly identified site on REST and promotes REST stability. Conversely, we find that epidermal growth factor, an extracellular signaling molecule that promotes neurogenesis, induces phosphorylation by extracellular signal-regulated (ERK/MAP) kinases at the same site on REST. The phosphorylation facilitates elimination of REST during the transition to neurons. Our mechanism helps explain the timing of REST degradation during neuronal differentiation.
Single cell sequencing reveals low levels of aneuploidy across mammalian tissues
Authors: Knouse Kristin A. , Wu Jie , Whittaker Charles A. , Amon Angelika
Published: September 2014

Significance

Aneuploidy refers to the gain or loss of individual chromosomes within a cell. Typically, aneuploidy is associated with detrimental consequences at both the cellular and organismal levels. However, reports of high levels of aneuploidy in the brain and liver suggested that aneuploidy might play a positive role in these organs. Here we use single cell sequencing to determine the prevalence of aneuploidy in somatic tissues. We find that aneuploidy is a rare occurrence in the liver and brain and is no more prevalent in these tissues than in skin. Our results demonstrate high karyotypic stability in somatic tissues, arguing against a role for aneuploidy in organ function and reinforcing its adverse effects at the cellular and organismal levels.
Valuation of Hospital Bed-Days Released by Infection Control Programs: A Comparison of Methods
Authors: Stewardson Andrew J. , Harbarth Stephan , Graves Nicholas ,   on behalf of the TIMBER Study Group
Published: September 2014

We performed a contingent valuation survey to elicit the opportunity cost of bed-days consumed by healthcare-associated infections in 11 European hospitals. The opportunity cost of a bed-day was significantly lower than the accounting cost; median values were €72 and €929, respectively (P < .001). Accounting methods overestimate the opportunity cost of bed-days.

Infect Control Hosp Epidemiol 2014;35(10):1294–1297
Over-representation of correlation analysis (ORCA): a method for identifying associations between variable sets
Authors: Pomyen Yotsawat , Segura Marcelo , Ebbels Timothy M. D. , Keun Hector C.
Published: September 2014

Motivation: Often during the analysis of biological data, it is of importance to interpret the correlation structure that exists between variables. Such correlations may reveal patterns of co-regulation that are indicative of biochemical pathways or common mechanisms of response to a related set of treatments. However, analyses of correlations are usually conducted by either subjective interpretation of the univariate covariance matrix or by applying multivariate modeling techniques, which do not take prior biological knowledge into account. Over-representation analysis (ORA) is a simple method for objectively deciding whether a set of variables of known or suspected biological relevance, such as a gene set or pathway, is more prevalent in a set of variables of interest than we expect by chance. However, ORA is usually applied to a set of variables differentiating a single experimental variable and does not take into account correlations.

Results: Over-representation of correlation analysis (ORCA) is a novel combination of ORA and correlation analysis that provides a means to test whether more associations exist between two specific groups of variables than expected by chance. The method is exemplified by application to drug sensitivity and microRNA expression data from a panel of cancer cell lines (NCI60). ORCA highlighted a previously reported correlation between sensitivity to alkylating anticancer agents and topoisomerase inhibitors. We also used this approach to validate microRNA clusters predicted by mRNA correlations. These observations suggest that ORCA has the potential to reveal novel insights from these data, which are not readily apparent using classical ORA.

Availability and implementation: The R code of the method is available at https://github.com/ORCABioinfo/ORCAcode

Supplementary information:  Supplementary data are available at Bioinformatics online.
CCharPPI web server: computational characterization of protein–protein interactions from structure
Authors: Moal Iain H. , Jiménez-García Brian , Fernández-Recio Juan
Published: September 2014

Summary: The atomic structures of protein–protein interactions are central to understanding their role in biological systems, and a wide variety of biophysical functions and potentials have been developed for their characterization and the construction of predictive models. These tools are scattered across a multitude of stand-alone programs, and are often available only as model parameters requiring reimplementation. This acts as a significant barrier to their widespread adoption. CCharPPI integrates many of these tools into a single web server. It calculates up to 108 parameters, including models of electrostatics, desolvation and hydrogen bonding, as well as interface packing and complementarity scores, empirical potentials at various resolutions, docking potentials and composite scoring functions.

Availability and implementation: The server does not require registration by the user and is freely available for non-commercial academic use at http://life.bsc.es/pid/ccharppi

Contact:  juanf@bsc.com
Risk assessment of the environmental impact of Norwegian Atlantic salmon farming
Authors: Taranger Geir Lasse , Karlsen Ørjan , Bannister Raymond John , Glover Kevin Alan , Husa Vivian , Karlsbakk Egil , Kvamme Bjørn Olav , Boxaspen Karin Kroon , Bjørn Pål Arne , Finstad Bengt , Madhun Abdullah Sami , Morton H. Craig , Svåsand Terje
Published: September 2014

Norwegian aquaculture has grown from its pioneering days in the 1970s to be a major industry. It is primarily based on culturing Atlantic salmon and rainbow trout and has the potential to influence the surrounding environment and wild populations. To evaluate these potential hazards, the Institute of Marine Research initiated a risk assessment of Norwegian salmon farming in 2011. This assessment has been repeated annually since. Here, we describe the background, methods and limitations of the risk assessment for the following hazards: genetic introgression of farmed salmon in wild populations, regulatory effects of salmon lice and viral diseases on wild salmonid populations, local and regional impact of nutrients and organic load. The main findings are as follows: (i) 21 of the 34 wild salmon populations investigated indicated moderate-to-high risk for genetic introgression from farmed escaped salmon. (ii) of 109 stations investigated along the Norwegian coast for salmon lice infection, 27 indicated moderate-to-high likelihood of mortality for salmon smolts while 67 stations indicated moderate-to-high mortality of wild sea trout. (iii) Viral disease outbreaks (pancreas disease, infectious pancreatic necrosis, heart and skeletal muscle inflammation, and cardiomyopathy syndrome) in Norwegian salmon farming suggest extensive release of viruses in many areas. However, screening of wild salmonids revealed low to very low prevalence of the causal viruses. (iv) From ∼500 yearly investigations of local organic loading under fish farms, only 2% of them displayed unacceptable conditions in 2013. The risk of eutrophication and organic load beyond the production area of the farm is considered low. Despite several limitations, especially limited monitoring data, this work represents one of the world’s first risk assessment of aquaculture. This has provided the Norwegian government with the basis upon which to take decisions for further development of the Norwegian aquaculture industry.
Evaluation of the Functionality of Five Different Soybean Proteins in Hot‐Press Wheat Flour Tortillas
Authors: Perez‐Carrillo Esther , Chew‐Guevara Ana A. , Heredia‐Olea Erick , Chuck‐Hernández Cristina , Serna‐Saldivar Sergio O.
Published: September 2014

Five different soybean protein sources were added to wheat flour to increase the protein content by 15–25%, and the resulting composite flours were optimally processed into hot‐press tortillas in a pilot plant. The rheological properties of composite flours were evaluated with the farinograph, alveograph, and other wheat quality tests. Tortilla‐making qualities of the control and soybean‐fortified flours were evaluated during dough handling, hot pressing, and baking. The resulting tortillas were tested in terms of yield, physical and chemical parameters, sensory properties, color, and objective and subjective texture. The soybean‐fortified tortillas had increased yields because of the higher dough water absorption and enhanced essential amino acid scores. Among the five different soybean proteins, the defatted soybean flour (SBM1) with the lowest fat absorption index and protein dispersibility index (PDI) and the soybean concentrate produced the best fortified tortillas. The protein meals with high PDI and relatively lower water absorption index (SBM3 and SBM4) produced sticky doughs, lower alveograph P/L values, and defective tortillas. All soybean proteins produced higher yields of tortillas with an enhanced protein quality and amount of dietary fiber.
Modeling End‐Use Quality in U.S. Soft Wheat Germplasm
Authors: Kiszonas Alecia M. , Fuerst E. Patrick , Morris Craig F.
Published: September 2014

End‐use quality in soft wheat (Triticum aestivum L.) can be assessed by a wide array of measurements, generally categorized into grain, milling, and baking characteristics. Samples were obtained from four U.S. regional nurseries. Selected parameters included test weight, kernel hardness, kernel size, kernel diameter, wheat protein, polyphenol oxidase activity, flour yield, break flour yield, flour ash content, milling score, flour protein content, flour SDS sedimentation volume, flour swelling volume, Rapid Visco Analyzer peak paste viscosity, solvent retention capacity (SRC) parameters, total and water‐extractable arabinoxylan (TAX and WEAX, respectively), and cookie diameter. The objectives were to model cookie diameter and lactic acid SRC as well as to compare exceptionally performing varieties for each quality parameter. Cookie diameter and lactic acid SRC were modeled by using multiple regression analyses and all of the aforementioned quality parameters. Cookie diameter was positively associated with peak paste viscosity and was negatively associated with or modeled by kernel hardness, flour protein content, sodium carbonate SRC, lactic acid SRC, and water SRC. Lactic acid SRC was positively modeled by break flour yield, milling score, flour SDS sedimentation volume, and sucrose SRC and was negatively modeled by flour protein content. Exceptionally high‐ and low‐performing varieties were selected on the basis of their responses to the aforementioned characteristics in each nursery. High‐ and low‐performing varieties exhibited notably wide variation in kernel hardness, break flour yield, milling score, sodium carbonate SRC, sucrose SRC, water SRC, TAX content, and cookie diameter. This high level of variation in variety performance can facilitate selection for improved quality based on exceptional performance in one or more of these traits. The models described allow a more focused approach toward predicting soft wheat quality.
Acantholytic Acanthoma of the Eyelid: Unusual Presentation
Authors: Mittal Ruchi , Mahapatra Samir
Published: September 2014

Acantholytic acanthoma is a benign epidermal tumor with a truncal predisposition and is not previously reported as an eyelid mass. A 63-year-old man, presented with a history of nodular masses of both his eyelid margin and eyelid surface of 3 years duration. Excision biopsy of lesion of eyelid margin was consistent with dermal nevus. Lesions of the eyelid surface displayed prominent acanthosis, acantholysis, and spongiosis. Variable hyperkeratosis and papillomatosis was also noted. There was absence of cytological atypia or mitoses. The microscopic picture was consistent with acantholytic acanthoma. The presence of extensive acantholysis in the present case excluded incidental focal epidermolytic hyperkeratosis and focal acantholytic dyskeratosis. Acantholytic vesiculobullous disorders and numerous acanthotic disorders, which are more common in the eyelid, need exclusion. To the authors’ best knowledge, as acantholytic acanthoma of the eyelid is not previously reported, they recommend that it should be included as differential diagnoses of benign epidermal lesions of eyelid.
Concurrent Endophthalmitis and Orbital Cellulitis From Metastatic Klebsiella pneumonia Liver Abscess
Authors: Davies Brett W. , Fante Robert G.
Published: September 2014

A 70-year-old Korean female with a history of Klebsiella pneumonia liver abscess was presented to the authors’ service with signs of endophthalmitis and orbital cellulitis. Vitreous biopsy confirmed K. pneumonia as the causative organism. With prolonged intravenous antibiotics and steroids, orbital symptoms resolved, but visual acuity remained at light perception. This is the first case in the literature to report on endophthalmitis and orbital cellulitis from K. pneumonia liver abscess.
Observational Outcome Results Following a Randomized Controlled Trial of Early Amino Acid Administration in Preterm Infants
Authors: van den Akker Chris H.P. , te Braake Frans W.J. , Weisglas‐Kuperus Nynke , van Goudoever Johannes B.
Published: September 2014

Objective:

Several reports have investigated amino acid administration in premature infants during the early postnatal phase. Most of these previous studies, however, have only evaluated short‐term in‐hospital outcomes. Our aim was to describe long‐term outcomes in premature infants previously subjected to different nutritional regimens in a randomized controlled trial. The primary outcome was survival without major disabilities, and the secondary outcomes included anthropometry and mental development.

Methods:

Infants born <32 weeks' gestation and <1500 g were randomized to receive glucose (n = 69) or glucose with 2.4 g · kg−1 · day−1 amino acids (n = 63) from birth. From postnatal day 3 onward, the nutritional intake was similar. At 2 years of corrected age, the surviving infants were assessed for neurodevelopmental outcome and anthropometry.

Results:

Ninety‐seven percent of the surviving infants were examined at follow‐up, with no overall effect on survival without major disabilities. Boys, however, had a normal outcome significantly more often if amino acids were administered from birth onward (crude odds ratio 3.8, 95% confidence interval 1.3–11.4) and following adjustment for confounders (odds ratio 6.2, 95% confidence interval 1.0–38.0). The secondary outcomes exhibited no differences in anthropometric data. The mental developmental index was lower in the small number of girls who survived without major disabilities following the early administration of amino acids.

Conclusions:

In this hypothesis‐generating outcome study, premature boys, but not girls, benefited from amino acid administration directly following birth. The observed lower mental developmental index in a subgroup of girls, however, warrants further studies.
Anxiety Symptoms and Disease Severity in Children and Adolescents With Crohn Disease
Authors: Reigada Laura C. , Hoogendoorn Claire J. , Walsh Lindsay C. , Lai Joanne , Szigethy Eva , Cohen Barry H. , Bao Ruijun , Isola Kimberly , Benkov Keith J.
Published: September 2014

Objectives:

Children and adolescents diagnosed as having Crohn disease (CD), a type of inflammatory bowel disease (IBD), have increased vulnerability for anxiety symptoms that may be related to disease‐related processes. The aims of this article are 3‐fold: to report the proportion of pediatric patients with CD whose self‐reported anxiety symptoms are indicative of distress, to describe the constellation of anxiety symptoms, and to examine the relation between anxiety and disease symptoms.

Methods:

Retrospective medical chart review was performed for 93 youths with CD (ages 9–18 years) who had completed the Screen for Child Anxiety Related Disorders during their gastroenterology visit. Medical records were reviewed for demographic and disease characteristics. the Harvey‐Bradshaw Index (HBI) was used as a measure of CD activity.

Results:

Thirty percent of the youths reported experiencing elevated anxiety symptoms (Screen for Child Anxiety Related Disorder score >20), and 50% had scored above the cutoff in 1 or more anxiety domains, with school anxiety, general anxiety, and separation anxiety symptoms reported most frequently. Youth rated with moderate/severe disease activity on the HBI (n = 4) self‐reported more anxiety symptoms compared with youth with inactive disease (n = 78,P= 0.03). Greater school anxiety was significantly associated with decreased well‐being (P= 0.003), more abdominal pain (P< 0.001), and the number of loose stools (P= 0.01). Having extraintestinal symptoms was significantly associated with higher somatic/panic anxiety (P=0.01).

Conclusions:

Implementing a brief anxiety screen in tertiary pediatric settings may be one approach to identify young patients with CD in distress. Health care providers should consider periodic assessment of school anxiety among youth with CD.
Exploiting short-term memory in soft body dynamics as a computational resource
Authors: Nakajima K. , Li T. , Hauser H. , Pfeifer R.
Published: September 2014

Soft materials are not only highly deformable, but they also possess rich and diverse body dynamics. Soft body dynamics exhibit a variety of properties, including nonlinearity, elasticity and potentially infinitely many degrees of freedom. Here, we demonstrate that such soft body dynamics can be employed to conduct certain types of computation. Using body dynamics generated from a soft silicone arm, we show that they can be exploited to emulate functions that require memory and to embed robust closed-loop control into the arm. Our results suggest that soft body dynamics have a short-term memory and can serve as a computational resource. This finding paves the way towards exploiting passive body dynamics for control of a large class of underactuated systems.
An extracellular polymer at the interface of magnetic bioseparations
Authors: Dhadge Vijaykumar L. , Morgado Patricia I. , Freitas Filomena , Reis Maria A. , Azevedo Ana , Aires-Barros Raquel , Roque A. Cecilia A.
Published: September 2014

FucoPol, a fucose-containing extracellular polysaccharide (EPS) produced by bacterium
Enterobacter
A47 using glycerol as the carbon source, was employed as a coating material for magnetic particles (MPs), which were subsequently functionalized with an artificial ligand for the capture of antibodies. The performance of the modified MPs (MP–EPS-22/8) for antibody purification was investigated using direct magnetic separation alone or combined with an aqueous two-phase system (ATPS) composed of polyethylene glycol (PEG) and dextran. In direct magnetic capturing, and using pure protein solutions of human immunoglobulin G (hIgG) and bovine serum albumin (BSA), MP–EPS-22/8 bound 120 mg hIgG g
−1
MPs, whereas with BSA only 10 ± 2 mg BSA g
−1
MPs was achieved. The hybrid process combining both the ATPS and magnetic capturing leads to a good performance for partitioning of hIgG in the desired phase as well as recovery by the magnetic separator. The MPs were able to bind 145 mg of hIgG g
−1
of particles which is quite high when compared with direct magnetic separation. The theoretical maximum capacity was calculated to be 410 ± 15 mg hIgG adsorbed g
−1
MPs with a binding affinity constant of 4.3 × 10
4
M
−1
. In multiple extraction steps, the MPs bound 92% of loaded hIgG with a final purity level of 98.5%. The MPs could easily be regenerated, recycled and re-used for five cycles with only minor loss of capacity. FucoPol coating allowed both electrostatic and hydrophobic interactions with the antibody contributing to enhance the specificity for the targeted products.
How to manage a revolution: Isaac Newton in the early twentieth century
Authors: Clarke Imogen
Published: September 2014

In the first half of the twentieth century, dramatic developments in physics came to be viewed as revolutionary, apparently requiring a complete overthrow of previous theories. British physicists were keen to promote quantum physics and relativity theory as exciting and new, but the rhetoric of revolution threatened science's claim to stability and its prestigious connections with Isaac Newton. This was particularly problematic in the first decades of the twentieth century, within the broader context of political turmoil, world war, and the emergence of modernist art and literature. This article examines how physicists responded to their cultural and political environment and worked to maintain disciplinary connections with Isaac Newton, emphasizing the importance of both the old and the new. In doing so they attempted to make the physics ‘revolution’ more palatable to a British public seeking a sense of permanence in a rapidly changing world.
An instability theory for the formation of ribbed moraine, drumlins and mega-scale glacial lineations
Authors: Fowler A. C. , Chapwanya M.
Published: September 2014

We present a theory for the coupled flow of ice, subglacial water and subglacial sediment, which is designed to represent the processes which occur at the bed of an ice sheet. The ice is assumed to flow as a Newtonian viscous fluid, the water can flow between the till and the ice as a thin film, which may thicken to form streams or cavities, and the till is assumed to be transported, either through shearing by the ice, squeezing by pressure gradients in the till, or by fluvial sediment transport processes in streams or cavities. In previous studies, it was shown that the dependence of ice sliding velocity on effective pressure provided a mechanism for the generation of bedforms resembling ribbed moraine, while the dependence of fluvial sediment transport on water film depth provides a mechanism for the generation of bedforms resembling mega-scale glacial lineations. Here, we combine these two processes in a single model, and show that, depending largely on the granulometry of the till, instability can occur in a range of types which range from ribbed moraine through three-dimensional drumlins to mega-scale glacial lineations.
Social transmission of tool use and tool manufacture in Goffin cockatoos (Cacatua goffini)
Authors: Auersperg A. M. I. , von Bayern A. M. I. , Weber S. , Szabadvari A. , Bugnyar T. , Kacelnik A.
Published: September 2014

Tool use can be inherited, or acquired as an individual innovation or by social transmission. Having previously reported individual innovative tool use and manufacture by a Goffin cockatoo, we used the innovator (Figaro, a male) as a demonstrator to investigate social transmission. Twelve Goffins saw either demonstrations by Figaro, or ‘ghost’ controls where tools and/or food were manipulated using magnets. Subjects observing demonstrations showed greater tool-related performance than ghost controls, with all three males in this group (but not the three females) acquiring tool-using competence. Two of these three males further acquired tool-manufacturing competence. As the actions of successful observers differed from those of the demonstrator, result emulation rather than high-fidelity imitation is the most plausible transmission mechanism.
Resource allocation during ontogeny is influenced by genetic, developmental and ecological factors in the horned beetle,
Onthophagus taurus
Authors: Schwab Daniel B. , Moczek Armin P.
Published: September 2014

Resource allocation trade-offs arise when developing organs are in competition for a limited pool of resources to sustain growth and differentiation. Such competition may constrain the maximal size to which structures can grow and may force a situation in which the evolutionary elaboration of one structure may only be possible at the expense of another. However, recent studies have called into question both the consistency and evolutionary importance of resource allocation trade-offs. This study focuses on a well-described trade-off between the horns and eyes of
Onthophagus
beetles and assesses the degree to which it is influenced by genetic, developmental and ecological conditions. Contrary to expectations, we observed that trade-off signatures (i) were mostly absent within natural populations, (ii) mostly failed to match naturally evolved divergences in horn investment among populations, (iii) were subject to differential changes in F
1
populations derived from divergent field populations and (iv) remained largely unaffected by developmental genetic manipulations of horn investment. Collectively, our results demonstrate that populations subject to different ecological conditions exhibit different patterns of, and differential plasticity in, resource allocation. Further, variation in ecological conditions, rather than canalized developmental mechanisms, may determine whether and to what degree morphological structures engage in resource allocation trade-offs.
Influenza virus non-structural protein NS1: interferon antagonism and beyond
Authors: Marc Daniel
Published: September 2014

Most viruses express one or several proteins that counter the antiviral defences of the host cell. This is the task of non-structural protein NS1 in influenza viruses. Absent in the viral particle, but highly expressed in the infected cell, NS1 dramatically inhibits cellular gene expression and prevents the activation of key players in the IFN system. In addition, NS1 selectively enhances the translation of viral mRNAs and may regulate the synthesis of viral RNAs. Our knowledge of the virus and of NS1 has increased dramatically during the last 15 years. The atomic structure of NS1 has been determined, many cellular partners have been identified and its multiple activities have been studied in depth. This review presents our current knowledge, and attempts to establish relationships between the RNA sequence, the structure of the protein, its ligands, its activities and the pathogenicity of the virus. A better understanding of NS1 could help in elaborating novel antiviral strategies, based on either live vaccines with altered NS1 or on small-compound inhibitors of NS1.
A Fast 3 ×NMatrix Multiply Routine for Calculation of Protein RMSD
Authors: Haque Imran S. , Beauchamp Kyle A. , Pande Vijay S.
Published: September 2014

The bottleneck for the rapid calculation of the root-mean-square deviation in atomic coordinates (RMSD) between pairs of protein structures for large numbers of conformations is the evaluation of a 3 ×N×N× 3 matrix product over conformation pairs. Here we describe two matrix multiply routines specialized for the 3 ×Ncase that are able to significantly outperform (by up to 3X) off-the-shelf high-performance linear algebra libraries for this computation, reaching machine limits on performance. The routines are implemented in C and Python libraries, and are available athttps://github.com/simtk/IRMSD.
Direct gamete sequencing reveals no evidence for segregation distortion in house mouse hybrids
Authors: Corbett-Detig Russell , Jacobs-Palmer Emily , Hartl Daniel , Hoekstra Hopi
Published: September 2014

Understanding the molecular basis of species formation is an important goal in evolutionary genetics, and Dobzhansky-Muller incompatibilities are thought to be a common source of postzygotic reproductive isolation between closely related lineages. However, the evolutionary forces that lead to the accumulation of such incompatibilities between diverging taxa are poorly understood. Segregation distorters are believed to be an important source of Dobzhansky-Muller incompatibilities betweenDrosophilaspecies and crop plants, but it remains unclear if these selfish genetic elements contribute to reproductive isolation in other species. Here, we collected viable sperm from first-generation hybrid male progeny ofMus musculus castaneusandM. m. domesticus, two subspecies of rodent in the earliest stages of speciation. We then genotyped millions of single nucleotide polymorphisms in these gamete pools and tested for a skew in the frequency of parental alleles across the genome. We show that segregation distorters are not measurable contributors to observed infertility in these hybrid males, despite sufficient statistical power to detect even weak segregation distortion with our novel method. Thus, reduced hybrid male fertility in crosses between these nascent species is attributable to other evolutionary forces.
Rate and cost of adaptation in theDrosophilagenome
Authors: Schiffels Stephan , Lässig Michael , Mustonen Ville
Published: September 2014

Recent studies have consistently inferred high rates of adaptive molecular evolution betweenDrosophilaspecies. At the same time, theDrosophilagenome evolves under different rates of recombination, which results in partial genetic linkage between alleles at neighboring genomic loci. Here we analyze how linkage correlations affect adaptive evolution. We develop a new inference method for adaptation that takes into account the effect on an allele at a focal site caused by neighboring deleterious alleles (background selection) and by neighboring adaptive substitutions (hitchhiking). Using complete genome sequence data and fine-scale recombination maps, we infer a highly heterogeneous scenario of adaptation inDrosophila. In high-recombining regions, about 50% of all amino acid substitutions are adaptive, together with about 20% of all substitutions in proximal intergenic regions. In low-recombining regions, only a small fraction of the amino acid substitutions are adaptive, while hitchhiking accounts for the majority of these changes. Hitchhiking of deleterious alleles generates a substantial collateral cost of adaptation, leading to a fitness decline of about 30/2N per gene and per million years in the lowest-recombining regions. Our results show how recombination shapes rate and efficacy of the adaptive dynamics in eukaryotic genomes.

Author Summary

Because recombination takes place at a limited rate, alleles at neighboring sites in a genome can remain genetically linked over evolutionary periods. In this paper, we show that evolutionary forces generated by genetic linkage have drastic consequences for the adaptive dynamics in low-recombining parts of theDrosophilagenome. Our study is based on a new method to analyze allele frequencies that is applicable to genome data at both high and low rates of recombination. We show that genes in low-recombining regions of theDrosophilagenome incur a substantial cost of adaptation, because deleterious alleles get fixed more frequently than under high recombination. This cost reduces rate and power of the adaptive process. Our results suggest that theDrosophilagenome has evolved to minimize this cost by placing genes under high adaptive pressure in high-recombining regions.
A Consistent Estimator of the Evolutionary Rate
Authors: Bartoszek Krzysztof , Sagitov Serik
Published: September 2014

We consider a branching particle system where particles reproduce according to the pure birth Yule process with the birth rate λ, conditioned on the observed number of particles to be equaln.Particles are assumed to move independently on the real line according to the Brownian motion with the local variance σ2. In this paper we treatnparticles as a sample of related species. The spatial Brownian motion of a particle describes the development of a trait value of interest (e.g. log-body-size). We propose an unbiased estimatorof the evolutionary rateρ2=σ2/λ. The estimatoris proportional to the sample variancecomputed fromntrait values. We find an approximate formula for the standard error ofbased on a neat asymptotic relation for the variance of.
Crossing the boundary between face-centred cubic and hexagonal close packed: the structure of nanosized cobalt is unraveled by a model accounting for shape, size distribution and stacking faults, allowing simulation of XRD, XANES and EXAFS
Authors: Longo Alessandro , Sciortino Luisa , Giannici Francesco , Martorana Antonino
Published: September 2014

The properties of nanostructured cobalt in the fields of magnetic, catalytic and biomaterials depend critically on Co close packing. This paper reports a structural analysis of nanosized cobalt based on the whole X-ray diffraction (XRD) pattern simulation allowed by the Debye equation. The underlying structural model involves statistical sequences of cobalt layers and produces simulated XRD powder patterns bearing the concurrent signatures of hexagonal and cubic close packing (h.c.p. and f.c.c.). Shape, size distribution and distance distribution between pairs of atoms are also modelled. The simulation algorithm allows straightforward fitting to experimental data and hence the quantitative assessment of the model parameters. Analysis of two samples having, respectively, h.c.p. and f.c.c. appearance is reported. Extended X-ray absorption fine-structure (EXAFS) and X-ray absorption near-edge structure (XANES) spectra are simulated on the basis of the model, giving a tool for the interpretation of structural data complementary to XRD. The outlined structural analysis provides a rigorous structural basis for correlations with magnetic and catalytic properties and an experimental reference forab initiomodelling of these properties.
Solving the structures of light-atom compounds with powder charge flipping
Authors: Šišak Jung Dubravka , Baerlocher Christian , McCusker Lynne B. , Yoshinari Tomohiro , Seebach Dieter
Published: September 2014

While the powder charge flipping (pCF) algorithm has been applied successfully to a variety of inorganic compounds, reports on its application to organic structures, in particular those consisting of light atoms only, are rare. To investigate the reason for this apparent incongruity, a series of light-atom structures were tested using the pCF algorithm implemented in the programSuperflip. The data sets, which covered varying degrees of reflection overlap, had resolutions of approximately 1 Å, and the structures ranged from 40 to 136 atoms per unit cell. Both centrosymmetric and noncentrosymmetric structures were investigated. A modified pCF approach, which was developed in a separate study, was tested on several compounds whose structures could not be solved by applying the basic pCF algorithm inSuperflip. The results show that organic structures with no heavy atoms and low symmetry do indeed test the limits of the pCF algorithm inSuperflip. The study has allowed a few guidelines for approaching such problems to be formulated.
Time-resolved coherent X-ray diffraction imaging of surface acoustic waves
Authors: Nicolas Jan-David , Reusch Tobias , Osterhoff Markus , Sprung Michael , Schülein Florian J. R. , Krenner Hubert J. , Wixforth Achim , Salditt Tim
Published: September 2014

Time-resolved coherent X-ray diffraction experiments of standing surface acoustic waves, illuminated under grazing incidence by a nanofocused synchrotron beam, are reported. The data have been recorded in stroboscopic mode at controlled and varied phase between the acoustic frequency generator and the synchrotron bunch train. At each time delay (phase angle), the coherent far-field diffraction pattern in the small-angle regime is inverted by an iterative algorithm to yield the local instantaneous surface height profile along the optical axis. The results show that periodic nanoscale dynamics can be imaged at high temporal resolution in the range of 50 ps (pulse length).
Collimation problem in small-angle X-ray scattering for anisotropic objects: statement and solution
Authors: Zakharov Denis D. , Smirnov Alexander V. , Fedorov Boris A.
Published: September 2014

The problem of removal of collimation distortion due to employing a slit collimation system in small-angle X-ray scattering experiments is considered for anisotropic objects in general and for orientated macromolecules in particular. A mathematical statement of the problem is presented, and two approaches to `de-smear' the experimental scattering intensity are described. The first method seeks the theoretical scattering intensity as a linear combination of two-dimensional basis functions (B splines). The combination coefficients are found using the χ2and two-dimensional curvature-minimization criteria. The second approach is based on the iterative Friedman method, which was generalized to be effective for the problem of interest. The described methods are applied to simulated and experimental data, and the results are discussed.
Phosphaturic mesenchymal tumor, mixed connective tissue type, non‐phosphaturic variant: Report of a case and review of 32 cases from the Japanese published work
Authors: Honda Rie , Kawabata Yuka , Ito Shusaku , Kikuchi Fumihito
Published: September 2014

Phosphaturic mesenchymal tumor, mixed connective tissue type (PMTMCT) is a rare neoplasm that can cause tumor‐induced osteomalacia due to overproduction of a phosphaturic hormone, fibroblast growth factor 23 (FGF23). We report here a case of subcutaneous PMTMCT, non‐phosphaturic variant, in the sole. We also review 32 Japanese cases of PMTMCT reported in detail. They occurred in 16 men and 15 women (one was unknown), with ages ranging 20–73 years (median, 48). Tumors were found in soft tissue, bone and sinuses in 17, 11 and four, respectively. A history of long‐standing osteomalacia was noted in all cases except two non‐phosphaturic variant cases. Serum FGF23 level was elevated in 11 of 12 cases examined. In terms of follow‐up information, metastases were found in four patients, and two patients died of disease. In conclusion, PMTMCT is histologically a benign lesion; however, there may be rare metastatic and malignant cases. Wider recognition of the histological features of this unique neoplasm would aid its distinction from the large number of mesenchymal tumors for which it may be mistaken and should enable correct diagnosis of tumors with osteomalacia.
Case of erythema nodosum associated with granulomatous mastitis probably due to Corynebacterium infection
Authors: Hida Tetsuya , Minami Mitsuyoshi , Kawaguchi Hidetoshi , Oshiro Yumi , Kubo Yoshiaki
Published: September 2014

Granulomatous mastitis (GM) is a rare chronic inflammatory breast disease that can be mistaken for a variety of inflammatory and neoplastic disorders of the breast. Erythema nodosum (EN) is a common panniculitis, and is often associated with a variety of diseases, yet coexistence of EN and GM is very rare. In this paper, we present a young Japanese woman with EN associated with GM probably due to Corynebacterium infection. Both lesions of EN and GM were successfully treated with oral minocycline and surgical drainage. To the best of our knowledge, this is the first case of EN associated with GM due to Corynebacterium infection in the English‐language published work.
Religious Reforming Currents in Sixteenth‐Century Italy: The Spirituali and the Tridentine Debates over Church Reform
Authors: Russell Camilla
Published: September 2014

The history of religious reform in sixteenth century Italy has been the subject of much scholarly debate in recent decades, as well as uncertainty about how best to conceptualise the period, so indelibly marked by epoch‐changing events, such as the Protestant Reformation (from 1517) and the Council of Trent (1545–1563). Reforming currents in Italy were swept along by these events, and indeed appear to have been overwhelmed by them. Commonly, these currents are explored for their theological nature and especially their heterodox, even Protestant, character. Less well studied is their role in the debates over organisational church reform. It is here that we can discern the tenacity of these currents well into the Tridentine period. This article explores key protagonists of reform, known as the spirituali, with particular reference to the humanist bishop, Ludovico Beccadelli, and his role in the debate over episcopal residence. Through an analysis of his contribution to this divisive debate at the Council of Trent, the article seeks to shed light on a strand of the spirituali that was both resilient and prominent in the battle for the future direction of the Catholic Church.
Evaluation of five antibiotics on larval gut bacterial diversity of Plutella xylostella (Lepidoptera: Plutellidae)
Authors: Lin Xiao‐Li , Kang Zhi‐Wei , Pan Qin‐Jian , Liu Tong‐Xian
Published: September 2014

Larvae of the diamondback moth, Plutella xylostella L. (Lepidoptera: Plutellidae), have rich microbial communities inhabiting the gut, and these bacteria contribute to the fitness of the pest. In this study we evaluated the effects of five antibiotics (rifampicin, ampicillin, tetracycline, streptomycin sulfate and chloramphenicol) on the gut bacterial diversity of P. xylostella larvae. We screened five different concentrations for each antibiotic in a leaf disc assay, and found that rifampicin and streptomycin sulfate at 3 mg/mL significantly reduced the diversity of the bacterial community, and some bacterial species could be rapidly eliminated. The number of gut bacteria in the rifampicin group and streptomycin sulfate group decreased more rapidly than the others. With the increase of antibiotic concentration, the removal efficiency was improved, whereas toxic effects became more apparent. All antibiotics reduced larval growth and development, and eventually caused high mortality, malformation of the prepupae, and hindered pupation and adult emergence. Among the five antibiotics, tetracycline was the most toxic and streptomycin sulfate was a relatively mild one. Some dominant bacteria were not affected by feeding antibiotics alone. Denaturing gradient gel electrophoresis graph showed that the most abundant and diverse bacteria in P. xylostella larval gut appeared in the cabbage feeding group, and diet change and antibiotics intake influenced gut flora abundance. Species diversity was significantly reduced in the artificial diet and antibiotics treatment groups. After feeding on the artificial diet with rifampicin, streptomycin sulfate and their mixture for 10 days, larval gut bacteria could not be completely removed as detected with the agarose gel electrophoresis method.