bluuebunny/crossref_metadata_2025 huggingface dataset:
Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice
Authors: Wang Huizhen , Larson Melissa , Jablonka-Shariff Albina , Pearl Christopher A. , Miller William L. , Conn P. Michael , Boime Irving , Kumar T. Rajendra
Published: April 2014

Significance

Although the two pituitary gonadotropins luteinizing hormone (LH) and FSH are synthesized in the same cell, gonadotrope, their intracellular trafficking and secretion pattern are distinct. LH is released as pulses via the regulated pathway, whereas FSH is constitutively secreted. Why this hormone-specific pattern has evolved and whether the target organ, the ovary, senses specific hormone release pattern is not understood. In this paper, a gonadotrope-specific sorting determinant on LH has been identified, and FSH was diverted into the LH secretory pathway in vivo. FSH released like LH from pituitary dramatically enhanced the ovarian responses. Our studies provide a molecular basis for the evolution of distinct patterns of gonadotropin secretion and explain the origin of estrus cycles in mammals.
Functional evolution of Erg potassium channel gating reveals an ancient origin for I
Kr
Authors: Martinson Alexandra S. , van Rossum Damian B. , Diatta Fortunay H. , Layden Michael J. , Rhodes Sarah A. , Martindale Mark Q. , Jegla Timothy
Published: April 2014

Significance

Ether-a-go-go related gene (Erg) family K
+
channels regulate excitability of muscle and neurons. However, mammalian and
Drosophila
Erg channels have distinctive gating phenotypes, suggesting divergent physiological roles. We examined the origins of Erg channel gating properties by investigating the functional evolution of the Erg family in Eumetazoa. We find that the mammalian I
Kr
-like Erg channel phenotype is ancestral. Thus, the gating features that specialize Erg1 for cardiac action potential repolarization may have had their origins in the slow wave contractions of early metazoans. These gating features, inactivation and slow deactivation, have been lost in the
Drosophila
Erg,
Caenorhabditis elegans
Erg, and some sea anemone (
Nematostella
) Ergs. Loss of the Ether-a-go-go domain, which regulates channel closing, accompanies and may in part explain phenotypic conversion.
Understanding the mechanism of proteasome 20S core particle gating
Authors: Latham Michael P. , Sekhar Ashok , Kay Lewis E.
Published: April 2014

Significance

The proteasome plays a critical role in regulating cellular homeostasis by degrading target protein substrates. Gating residues that are part of the barrel-like proteasome structure provide a barrier to prevent inadvertent proteolysis. With NMR spectroscopy, the mechanism by which the gates interconvert between open and closed states is studied. We show that collisions with water molecules provide a driving force for gate interconversion and that the process takes place via many small steps that involve protein segments smaller than 4 Å. The effect of cellular lysate on proteasome gating is explored, establishing that gating equilibria and kinetics are not perturbed relative to buffer solutions under conditions of similar viscosity.
Radiocarbon evidence for alternating northern and southern sources of ventilation of the deep Atlantic carbon pool during the last deglaciation
Authors: Skinner Luke C. , Waelbroeck Claire , Scrivner Adam E. , Fallon Stewart J.
Published: April 2014

Significance

This study sheds light on the mechanisms of deglacial atmospheric CO
2
rise and, more specifically, on the hypothesized role of a “bipolar seesaw” in deep Atlantic ventilation. Comparing new high-resolution radiocarbon reconstructions from the Northeast Atlantic with existing data from the Southern Ocean, we show that a bipolar ventilation seesaw did indeed operate during the last deglaciation. Whereas today the deep Atlantic’s carbon pool is “flushed” from the north by North Atlantic Deep Water export, it was flushed instead from the south during Heinrich Stadial 1 and the Younger Dryas, in time with sustained atmospheric CO
2
rise.
Oxytocin promotes group-serving dishonesty
Authors: Shalvi Shaul , De Dreu Carsten K. W.
Published: April 2014

Significance

Very little is known about the biological foundations of immoral behavior. We report here the results of a double-blind, placebo-controlled experiment showing that the hormone oxytocin promotes group-serving dishonesty. Compared with participants receiving placebo, participants receiving oxytocin lied more to benefit their groups, did so quicker, and did so without expectation of reciprocal dishonesty from their group members. A control setting ruled out that oxytocin drives self-serving dishonesty. These findings support the functional approach to morality and reveal the underlying biological circuitries associated with group-serving dishonesty.
IL-15 adjuvanted multivalent vaccinia-based universal influenza vaccine requires CD4
+
T cells for heterosubtypic protection
Authors: Valkenburg Sophie A. , Li Olive T. W. , Mak Polly W. Y. , Mok Chris K. P. , Nicholls John M. , Guan Yi , Waldmann Thomas A. , Peiris J. S. Malik , Perera Liyanage P. , Poon Leo L. M.
Published: April 2014

Significance

We present a novel vaccine that elicits protective immune responses against many different influenza viruses belonging to both group 1 and 2 lineages. The vaccine uses a live vaccinia virus that expresses multiple H5N1 influenza viral proteins and the cytokine IL-15 to stimulate the immune system. The vaccine was able to induce T-cell immune responses that recognize different influenza viruses and these immune responses were augmented when exposed to a challenge virus, resulting in protection against a lethal disease. Vaccine-induced CD4
+
T cells that coordinate immune responses were found to be more important than CD8
+
T cells in conferring protection. Our vaccine provides a promising strategy for universal protection against novel and emerging influenza viruses.
Observing (non)linear lattice dynamics in graphite by ultrafast Kikuchi diffraction
Authors: Liang Wenxi , Vanacore Giovanni M. , Zewail Ahmed H.
Published: April 2014

Significance

Mechanical, electrical, and thermal properties of materials are governed by the nature of constituent atoms and their motions. Mapping atomic motions in the nonequilibrium regime, and thus the linear and nonlinear responses to stimuli, is nontrivial to achieve. Here, we report the methodology of ultrafast electron diffraction, enabling visualization of the atoms in motion. By using a special variant called Kikuchi diffraction, we map out the response of the lattice of nanoscale graphite. Following an impulsive excitation, two types of motions are resolved, one involving the reflections of strain between the two surfaces and the other involving planes of atoms in the transverse direction. The approach presented here has the potential for a wide range of applications.
Chapter 2. The p-model of data and evidence in linguistics
Authors: Kertész András , Rákosi Csilla
Published: April 2014

The p-model is a metatheoretical approach to linguistic theorising that has been designed to capture the nature of linguistic data and evidence in an unorthodox and novel, but well-motivated and effective way. Its starting point is the insight that the latest literature on linguistic data and evidence acknowledged the uncertainty of the latter as their key feature. Since the main characteristic of plausible inferences is that they facilitate drawing conclusions from uncertain premises, and since chains of plausible inferences constitute the main body of the process of plausible argumentation, the basic idea of the p-model is that the structure of linguistic theories is based on various techniques of plausible argumentation. This chapter summarises the main hypotheses of the p-model, which the case studies in the volume are expected to apply to various linguistic theories.
Chapter 5. Hungarian verbs of natural phenomena with explicit and implicit subject arguments
Authors: Németh T. Enikő
Published: April 2014

The present chapter has two main aims. First, it attempts to provide a novel account for the occurrence of Hungarian verbs of natural phenomena with subject arguments. The problem which the present chapter wants to resolve is that there is an inconsistency between the previous explanations of the behaviour of verbs of natural phenomena with and without an explicit subject and the data. The previous approaches have considered the Hungarian verbs of natural phenomena subjectless, although data from various direct sources (such as written corpora, intuition, introspection, and spoken discourses) testify to occurrences of verbs of natural phenomena with explicit subjects. To eliminate this inconsistency, the chapter argues for a new, unified approach, according to which Hungarian verbs of natural phenomena have subject arguments in their lexical-semantic representations which can (or even should) be lexically unrealised in some contexts, while in others they can be explicitly expressed and contextual, grammatical as well as lexical-semantic factors together license the implicit or explicit occurrence of subject arguments. Second, applying Kertész & Rákosi’s (this volume, 2012) p-model, the chapter aims to reflect on a metalinguistic level on how the proposed explanation has been reached in the course of the research as well as how the new account can resolve the above mentioned problem.
Chapter 6. The development of a taxonomy of verbal disagreements in the light of the p-model
Authors: Koczogh Helga Vanda
Published: April 2014

The main objective of this chapter is to find a category system that is the most capable of describing Hungarian disagreement based on certain criteria set beforehand. As none of the rival approaches to disagreement to be introduced in this chapter seem to satisfy each criterion, a new taxonomy is proposed. Distinguishing between strategies and pragmatic force modifiers (PFMs), this new category system is more reliable and more capable of capturing the complex nature of (Hungarian) disagreements that the rival models. A detailed description of the metatheoretical research is provided including a step-by-step description of the analytical procedure(s) employed. By describing each step of the research along with the decisions and re-evaluations of the information at hand as well as the p-context, the chapter demonstrates the cyclic, retrospective and prismatic nature of the plausible argumentation process.
Chapter 7. A case of disagreement
Authors: Rákosi György
Published: April 2014

The chapter discusses the so-called Hungarian reduplicating particle verb construction that has generated some interest in the pertinent generative literature on Hungarian. This literature is divided over whether reduplicating particles can bear plural morphology in the presence of a third person plural oblique associate or not: some accept and some reject the resulting agreeing reduplicating particle verb construction, thus creating a par excellence context of data inconsistency. The chapter offers a detailed and critical overview of the literature, and presents some novel arguments in an effort to find a paraconsistent solution to this problem within the framework of the p-model of Kertész and Rákosi (2012). This solution rests and on the claim that the plural and the non-plural reduplicating particle verb constructions are radically different in their grammar, since the particle only acts as a pronominal in the case of the former construction type. The pronominal use of the particle is a marked option, rendering the agreeing reduplicating particle verb construction a marked phenomenon of Hungarian grammar.
Chapter 8. A plausibility-based model of shifted indexicals
Authors: Vecsey Zoltán
Published: April 2014

In his groundbreaking formal work on context-dependent expressions, Kaplan (1989a) argued that the conventional meaning of natural language indexicals cannot be modified by sentential operators. Kaplan’s original theory, however, has been recently challenged by empirical studies. It turned out that in certain languages, for example in Amharic and Zazaki, attitude operators are able to modify the meaning of indexicals. Some of these empirical findings appear to be clearly inconsistent with the Kaplanian account. From a metatheoretical point of view, the current debate about the operator-sensitivity of indexicals can also be interpreted as a debate about the role of linguistic data. In following the p-model and considering linguistic data as statements with plausibility values, one can make some progress in this field of research.
Chapter 9. Thought experiments and real experiments as converging data sources in pragmatics
Authors: Kertész András , Rákosi Csilla
Published: April 2014

The aim of the present chapter is to reconstruct the relationship between thought experiments and real experiments in pragmatics. In the first part, Searle’s (1969) thought experiment on Kennst du das Land, wo die Zitronen blühn? is analysed with the help of the p-model. The second part reconstructs the argumentation structure of the real experiments reported on in Holtgraves & Ashley (2001), and shows that the latter and Searle’s thought experiment closely interact. Basically, their relationship is characterised by the dynamic process of the cyclic, prismatic and retrospective re-evalutation of information in the sense of the p-model. However, they have different strengths and weaknesses. Accordingly, the generalised finding is that the conscious integration of real and thought experiments as data sources within some research may considerably enhance the reliability of pragmatic hypotheses.
Infectious Salmon Anemia (ISA) Virus: Infectivity in Seawater under Different Physical Conditions
Authors: Vike Siri , Oelckers Karin , Duesund Henrik , Erga Svein Rune , Gonzalez Javier , Hamre Børge , Frette Øyvind , Nylund Are
Published: April 2014

Infectious salmon anemia (ISA) virus (genus Isavirus, family Orthomyxoviridae), present in all major salmon producing countries, is the causative agent for a serious and commercially important disease affecting Atlantic Salmon Salmo salar. Nearly all ISA outbreaks occur in the marine production phase and knowledge about survival time for ISA virions in seawater is crucial for an adequate strategy to combat the disease. To acquire knowledge about this important factor, a study of ISA virus exposed to four different physical conditions was carried out. The virions’ survival was tested in sterile seawater, sterile seawater with normal ultraviolet light radiation (UVR), natural seawater, and natural seawater with UVR. During the 72-h experiment both presence of ISA virus RNA and the infectivity of ISA virions were monitored. The result of this study showed that the infectivity of ISA virions is lost within 3 h of exposure to natural seawater or sterile seawater with UVR. However, it was possible to detect ISA virus RNA throughout the experimental period. This indicates that the effect of both UVR and biological activity of natural seawater limits the survival time of ISA virions under normal conditions. The survival time of ISA virions in sterile seawater was less than 24 h. Based on the available literature and the present study it is not very likely that passive horizontal transmission in seawater over long distances can occur. This is due to the following factors: (1) the effect of UVR and biological activity on ISA virions infectivity found in the present study, (2) the speed and dilution effect in seawater currents in salmon farming areas, (3) the temperature during the major outbreak periods, and (4) the need for an infective dose of ISA virions to reach naive Atlantic Salmon.

Received August 22, 2013; accepted November 7, 2013
Interleukin-7 receptor mutants initiate early T cell precursor leukemia in murine thymocyte progenitors with multipotent potential
Authors: Treanor Louise M. , Zhou Sheng , Janke Laura , Churchman Michelle L. , Ma Zhijun , Lu Taihe , Chen Shann-Ching , Mullighan Charles G. , Sorrentino Brian P.
Published: April 2014

Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) exhibits lymphoid, myeloid, and stem cell features and is associated with a poor prognosis. Whole genome sequencing of human ETP-ALL cases has identified recurrent mutations in signaling, histone modification, and hematopoietic development genes but it remains to be determined which of these abnormalities are sufficient to initiate leukemia. We show that activating mutations in the interleukin-7 receptor identified in human pediatric ETP-ALL cases are sufficient to generate ETP-ALL in mice transplanted with primitive transduced thymocytes from p19Arf−/− mice. The cellular mechanism by which these mutant receptors induce ETP-ALL is the block of thymocyte differentiation at the double negative 2 stage at which myeloid lineage and T lymphocyte developmental potential coexist. Analyses of samples from pediatric ETP-ALL cases and our murine ETP-ALL model show uniformly high levels of LMO2 expression, very low to undetectable levels of BCL11B expression, and a relative lack of activating NOTCH1 mutations. We report that pharmacological blockade of Jak–Stat signaling with ruxolitinib has significant antileukemic activity in this ETP-ALL model. This new murine model recapitulates several important cellular and molecular features of ETP-ALL and should be useful to further define novel therapeutic approaches for this aggressive leukemia.
Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy
Authors: Fan Xiaozhou , Quezada Sergio A. , Sepulveda Manuel A. , Sharma Padmanee , Allison James P.
Published: April 2014

Cytotoxic T lymphocyte antigen-4 (CTLA-4) blockade with a monoclonal antibody yields durable responses in a subset of cancer patients and has been approved by the FDA as a standard therapy for late-stage melanoma. We recently identified inducible co-stimulator (ICOS) as a crucial player in the antitumor effects of CTLA-4 blockade. We now show that concomitant CTLA-4 blockade and ICOS engagement by tumor cell vaccines engineered to express ICOS ligand enhanced antitumor immune responses in both quantity and quality and significantly improved rejection of established melanoma and prostate cancer in mice. This study provides strong support for the development of combinatorial therapies incorporating anti–CTLA-4 and ICOS engagement.
CRTAM controls residency of gut CD4+CD8+ T cells in the steady state and maintenance of gut CD4+ Th17 during parasitic infection
Authors: Cortez Victor S. , Cervantes-Barragan Luisa , Song Christina , Gilfillan Susan , McDonald Keely G. , Tussiwand Roxane , Edelson Brian T. , Murakami Yoshinori , Murphy Kenneth M. , Newberry Rodney D. , Sibley L. David , Colonna Marco
Published: April 2014

Retention of lymphocytes in the intestinal mucosa requires specialized chemokine receptors and adhesion molecules. We find that both CD4+CD8+ and CD4+ T cells in the intestinal epithelium, as well as CD8+ T cells in the intestinal mucosa and mesenteric lymph nodes, express the cell adhesion molecule class I–restricted T cell–associated molecule (Crtam) upon activation, whereas the ligand of Crtam, cell adhesion molecule 1 (Cadm1), is expressed on gut CD103+DCs. Lack of Crtam–Cadm1 interactions in Crtam−/− and Cadm1−/− mice results in loss of CD4+CD8+ T cells, which arise from mucosal CD4+ T cells that acquire a CD8 lineage expression profile. After acute oral infection with Toxoplasma gondii, both WT and Crtam−/− mice mounted a robust TH1 response, but markedly fewer TH17 cells were present in the intestinal mucosa of Crtam−/− mice. The almost exclusive TH1 response in Crtam−/− mice resulted in more efficient control of intestinal T. gondii infection. Thus, Crtam–Cadm1 interactions have a major impact on the residency and maintenance of CD4+CD8+ T cells in the gut mucosa in the steady state. During pathogenic infection, Crtam–Cadm1 interactions regulate the dynamic equilibrium between newly formed CD4+ T cells and their retention in the gut, thereby shaping representation of disparate CD4+ T cell subsets and the overall quality of the CD4+ T cell response.
European Society for Pediatric Gastroenterology, Hepatology, and Nutrition/European Society for Pediatric Infectious Diseases Evidence‐Based Guidelines for the Management of Acute Gastroenteritis in Children in Europe
Authors: Guarino Alfredo , Ashkenazi Shai , Gendrel Dominique , Lo Vecchio Andrea , Shamir Raanan , Szajewska Hania
Published: April 2014

Objectives:

These guidelines update and extend evidence‐based indications for the management of children with acute gastroenteritis in Europe.

Methods:

The guideline development group formulated questions, identified data, and formulated recommendations. The latter were graded with the Muir Gray system and, in parallel, with the Grading of Recommendations, Assessment, Development and Evaluations system.

Results:

Gastroenteritis severity is linked to etiology, and rotavirus is the most severe infectious agent and is frequently associated with dehydration. Dehydration reflects severity and should be monitored by established score systems. Investigations are generally not needed. Oral rehydration with hypoosmolar solution is the major treatment and should start as soon as possible. Breast‐feeding should not be interrupted. Regular feeding should continue with no dietary changes including milk. Data suggest that in the hospital setting, in non–breast‐fed infants and young children, lactose‐free feeds can be considered in the management of gastroenteritis. Active therapy may reduce the duration and severity of diarrhea. Effective interventions include administration of specific probiotics such as Lactobacillus GG or Saccharomyces boulardii, diosmectite or racecadotril. Anti‐infectious drugs should be given in exceptional cases. Ondansetron is effective against vomiting, but its routine use requires safety clearance given the warning about severe cardiac effects. Hospitalization should generally be reserved for children requiring enteral/parenteral rehydration; most cases may be managed in an outpatients setting. Enteral rehydration is superior to intravenous rehydration. Ultrarapid schemes of intravenous rehydration are not superior to standard schemes and may be associated with higher readmission rates.

Conclusions:

Acute gastroenteritis is best managed using a few simple, well‐defined medical interventions.
Mucosal Healing in Children With Treated Celiac Disease
Authors: Ghazzawi Youssef , Rubio‐Tapia Alberto , Murray Joseph A. , Absah Imad
Published: April 2014

Objectives:

Limited data suggest complete mucosal healing in treated children with celiac disease (CD), but recent data from adult endoscopic biopsies have shown substantial numbers with persistent mucosal injury. We aimed to assess the rate of mucosal healing and indications for repeat small bowel (SB) biopsy in children with CD.

Methods:

We retrospectively reviewed records of children (ages 1–18 years) with CD who underwent a second SB biopsy. All of the children were seen at Mayo Clinic (Rochester, MN) from January 1997 through June 2013.

Results:

Forty children were identified (14 boys); average age at diagnosis was 8.5 years. Indications for second SB biopsy were abdominal pain (n = 20), diarrhea (n = 7), constipation (n = 5), non–celiac‐related concern (n = 2), follow‐up (n = 5), and persistent serology (n = 1). Average time between biopsies was 24 months (range 4–120 months). Histology on the second biopsy showed complete healing (n = 25), intraepithelial lymphocytes (n = 9), and persistent villous atrophy (n = 6). Of these, 3 patients had partial villous atrophy and 3 had with complete villous atrophy. Persistent villous atrophy was observed in 2 of 20 patients with abdominal pain and 1 of 7 with diarrhea. All of the patients with persistent constipation (n = 5) had complete resolution.

Conclusions:

Mucosal healing in children with CD may not be complete as previously assumed. Abdominal pain was the most common indication for repeating the SB biopsy. Persistence of abdominal pain, diarrhea, and constipation was poorly associated with persistence of mucosal injury.
The genetical theory of social behaviour
Authors: Lehmann Laurent , Rousset François
Published: April 2014

We survey the population genetic basis of social evolution, using a logically consistent set of arguments to cover a wide range of biological scenarios. We start by reconsidering Hamilton's (Hamilton 1964J. Theoret. Biol.7, 1–16 (doi:10.1016/0022-5193(64)90038-4)) results for selection on a social trait under the assumptions of additive gene action, weak selection and constant environment and demography. This yields a prediction for the direction of allele frequency change in terms of phenotypic costs and benefits and genealogical concepts of relatedness, which holds for any frequency of the trait in the population, and provides the foundation for further developments and extensions. We then allow for any type of gene interaction within and between individuals, strong selection and fluctuating environments and demography, which may depend on the evolving trait itself. We reach three conclusions pertaining to selection on social behaviours under broad conditions. (i) Selection can be understood by focusing on a one-generation change in mean allele frequency, a computation which underpins the utility of reproductive value weights; (ii) in large populations under the assumptions of additive gene action and weak selection, this change is of constant sign for any allele frequency and is predicted by a phenotypic selection gradient; (iii) under the assumptions of trait substitution sequences, such phenotypic selection gradients suffice to characterize long-term multi-dimensional stochastic evolution, with almost no knowledge about the genetic details underlying the coevolving traits. Having such simple results about the effect of selection regardless of population structure and type of social interactions can help to delineate the common features of distinct biological processes. Finally, we clarify some persistent divergences within social evolution theory, with respect to exactness, synergies, maximization, dynamic sufficiency and the role of genetic arguments.
Evolutionary dynamics ofn-player games played by relatives
Authors: Ohtsuki Hisashi
Published: April 2014

One of the core concepts in social evolution theory is kin selection. Kin selection provides a perspective to understand how natural selection operates when genetically similar individuals are likely to interact. A family-structured population is an excellent example of this, where relatives are engaged in social interactions. Consequences of such social interactions are often described in game-theoretical frameworks, but there is a growing consensus that a naive inclusive fitness accounting with dyadic relatedness coefficients are of limited use when non-additive fitness effects are essential in those situations. Here, I provide a general framework to analyse multiplayer interactions among relatives. Two important results follow from my analysis. First, it is generally necessary to know then-tuple genetic association of family members whennindividuals are engaged in social interactions. However, as a second result, I found that, for a special class of games, we need only measures of lower-order genetic association to fully describe its evolutionary dynamics. I introduce the concept ofdegreeof the game and show how this degree is related to the degree of genetic association.
Hamilton's rule and the causes of social evolution
Authors: Bourke Andrew F. G.
Published: April 2014

Hamilton's rule is a central theorem of inclusive fitness (kin selection) theory and predicts that social behaviour evolves under specific combinations of relatedness, benefit and cost. This review provides evidence for Hamilton's rule by presenting novel syntheses of results from two kinds of study in diverse taxa, including cooperatively breeding birds and mammals and eusocial insects. These are, first, studies that empirically parametrize Hamilton's rule in natural populations and, second, comparative phylogenetic analyses of the genetic, life-history and ecological correlates of sociality. Studies parametrizing Hamilton's rule are not rare and demonstrate quantitatively that (i) altruism (net loss of direct fitness) occurs even when sociality is facultative, (ii) in most cases, altruism is under positive selection via indirect fitness benefits that exceed direct fitness costs and (iii) social behaviour commonly generates indirect benefits by enhancing the productivity or survivorship of kin. Comparative phylogenetic analyses show that cooperative breeding and eusociality are promoted by (i) high relatedness and monogamy and, potentially, by (ii) life-history factors facilitating family structure and high benefits of helping and (iii) ecological factors generating low costs of social behaviour. Overall, the focal studies strongly confirm the predictions of Hamilton's rule regarding conditions for social evolution and their causes.
How Darwinian is cultural evolution?
Authors: Claidière Nicolas , Scott-Phillips Thomas C. , Sperber Dan
Published: April 2014

Darwin-inspired population thinking suggests approaching culture as a population of items of different types, whose relative frequencies may change over time. Three nested subtypes of populational models can be distinguished: evolutionary, selectional and replicative. Substantial progress has been made in the study of cultural evolution by modelling it within the selectional frame. This progress has involved idealizing away from phenomena that may be critical to an adequate understanding of culture and cultural evolution, particularly the constructive aspect of the mechanisms of cultural transmission. Taking these aspects into account, we describe cultural evolution in terms ofcultural attraction, which is populational and evolutionary, but only selectional under certain circumstances. As such, in order to model cultural evolution, we must not simply adjust existing replicative or selectional models but we should rathergeneralizethem, so that, just as replicator-based selection is one form that Darwinian selection can take, selection itself is one of several different forms that attraction can take. We present an elementary formalization of the idea of cultural attraction.
Prevalence of IncI1-Iγ and IncFIA-FIB type plasmids in extended-spectrum β-lactamase-producing Klebsiella pneumoniae strains isolated from the NICU of a North Indian hospital
Authors: Ali Saeedut Zafar , Ali Syed Manazir , Khan Asad U.
Published: April 2014

We studied the molecular mechanism of resistance in extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae isolated from a neonatal intensive care unit (NICU) of one of the hospitals in North India. A total of 3000 clinical samples were collected from a NICU (January 2009 to February 2011), of which 523 strains were K. pneumoniae positive and 262 of them were ESBL-producing K. pneumoniae strains. All of the ESBL-producing clinical isolates were susceptible to carbapenems. However, the majority of the clinical isolates (30–96 %) were resistant to a wide range of antibiotics including antibiotic/inhibitor combinations. The MIC values confirmed that these isolates were highly resistant to cephalosporins and aztreonam. In the 262 ESBL-producing K. pneumoniae isolates, 15 different enterobacterial repetitive intergenic consensus (ERIC)-PCR-typed phylogenetic groups were identified and reconfirmed by PFGE. Characterization of plasmids from each representative member of these phylogenetic groups revealed the presence of three plasmids of different sizes. Conjugation experiments confirmed the presence of different resistance markers only on the 154 kb plasmid. PCR amplification and sequence analysis revealed that bla
CTX-M-3, bla
TEM-1, bla
SHV-1, bla
OXA-1 and armA were the predominant resistance markers. Plasmid-replicon typing showed that IncI1-Iγ and IncFIA-FIB types are the most prevalent. This study shows the co-existence of multiple ESBL-encoding genes and their polyclonal dissemination among K. pneumoniae clinical isolates in the NICU of a North Indian hospital.
Structural determinants of the interaction between the Haemophilus influenzae Hap autotransporter and fibronectin
Authors: Spahich Nicole A. , Kenjale Roma , McCann Jessica , Meng Guoyu , Ohashi Tomoo , Erickson Harold P. , St. Geme Joseph W.
Published: April 2014

Haemophilus influenzaeis a Gram-negative cocco-bacillus that initiates infection by colonizing the upper respiratory tract. Hap is anH. influenzaeserine protease autotransporter protein that mediates adherence, invasion and microcolony formation in assays with human epithelial cells and is presumed to facilitate the process of colonization. Additionally, Hap mediates adherence to fibronectin, laminin and collagen IV, extracellular matrix (ECM) proteins that are present in the respiratory tract and are probably important targets forH. influenzaecolonization. The region of Hap responsible for adherence to ECM proteins has been localized to the C-terminal 511 aa of the Hap passenger domain (HapS). In this study, we characterized the structural determinants of the interaction between HapSand fibronectin. Using defined fibronectin fragments, we established that Hap interacts with the fibronectin repeat fragment called FNIII(1–2). Using site-directed mutagenesis, we found a series of motifs in the C-terminal region of HapSthat contribute to the interaction with fibronectin. Most of these motifs are located on the F1 and F3 faces of the HapSstructure, suggesting that the F1 and F3 faces may be responsible for the HapS–fibronectin interaction.
Whole-Cell Patch-Clamp Recordings of Ca2+ Currents from Isolated Neonatal Mouse Dorsal Root Ganglion (DRG) Neurons
Authors: Gandini María A. , Sandoval Alejandro , Felix Ricardo
Published: April 2014

Primary culture of sensory neurons from dorsal root ganglia (DRGs) is a widely used model for studying Ca2+ channels. DRG neurons can be collected from neonate or adult mice; the production of cultures can take a couple of hours, and cells so derived can be used almost immediately or maintained for as long as 1 wk. This method allows the isolation of neurons for numerous experimental purposes, including whole-cell patch-clamp recording. The purpose of this protocol is to provide a description of methods commonly used for the harvest and growth of DRG neonatal neurons as well as for recording whole-cell currents through voltage-sensitive Ca2+ channels in these cells.
Immunopanning of Retrograde-Labeled Corticospinal Motor Neurons from Early Postnatal Rodents
Authors: Mandemakers Wim
Published: April 2014

Here we describe a method to purify corticospinal motor neurons (CSMNs). It combines the versatility of retrograde labeling with the advantages of immunopanning. Rat cortices with CSMNs that have been labeled with cholera toxin beta (CTB) are dissected and dissociated, and the CSMNs are specifically purified via immunopanning with an anti-CTB antibody. We show the efficacy of this method in early rat pups by purifying CSMNs to >99% purity. The method can be used to highly purify any neuronal cell type whose projections can be selectively labeled via retrograde tracing.
Strategies to Achieve Conditional Gene Mutation in Mice
Authors: Gierut Jessica J. , Jacks Tyler E. , Haigis Kevin M.
Published: April 2014

The laboratory mouse is an ideal model organism for studying disease because it is physiologically similar to human and also because its genome is readily manipulated. Genetic engineering allows researchers to introduce specific loss-of-function or gain-of-function mutations into genes and then to study the resulting phenotypes in an in vivo context. One drawback of using traditional transgenic and knockout mice to study human diseases is that many mutations passed through the germline can profoundly affect development, thus impeding the study of disease phenotypes in adults. New technology has made it possible to generate conditional mutations that can be introduced in a spatially and/or temporally restricted manner. Mouse strains carrying conditional mutations represent valuable experimental models for the study of human diseases and they can be used to develop strategies for prevention and treatment of these diseases. In this article, we will describe the most widely used DNA recombinase systems used to achieve conditional gene mutation in mouse models and discuss how these systems can be employed in vivo.
Purification and Culture of Corticospinal Motor Neurons
Authors: Mandemakers Wim
Published: April 2014

Corticospinal motor neurons (CSMNs) residing in cortical layer V of the mammalian brain project their axons to the spinal cord, where they connect with spinal motor neurons (SMNs) located in the ventral horn of the spinal cord. CSMNs and SMNs control voluntary movements, and their importance becomes obvious in situations where this network breaks down (i.e., in amyotrophic lateral sclerosis [ALS] and after spinal cord injury). Here we provide an overview of recent progress in the anatomical, morphological, and genetic characterization of developing CSMNs, as well as their survival requirements. We also describe model systems used to study CSMNs and introduce an immunopanning procedure for the purification and culture of CSMNs. Although these procedures have so far been used to purify only rodent CSMNs, in principle they should work to purify CSMNs from any vertebrate species, as well any type of central nervous system (CNS) or peripheral nervous system (PNS) neuron that can be retrograde labeled.
Dynamics and Organization of Cortical Microtubules as Revealed by Superresolution Structured Illumination Microscopy
Authors: Komis George , Mistrik Martin , Šamajová Olga , Doskočilová Anna , Ovečka Miroslav , Illés Peter , Bartek Jiri , Šamaj Jozef
Published: April 2014

Plants employ acentrosomal mechanisms to organize cortical microtubule arrays essential for cell growth and differentiation. Using structured illumination microscopy (SIM) adopted for the optimal documentation of Arabidopsis (Arabidopsis thaliana) hypocotyl epidermal cells, dynamic cortical microtubules labeled with green fluorescent protein fused to the microtubule-binding domain of the mammalian microtubule-associated protein MAP4 and with green fluorescent protein-fused to the alpha tubulin6 were comparatively recorded in wild-type Arabidopsis plants and in the mitogen-activated protein kinase mutant mpk4 possessing the former microtubule marker. The mpk4 mutant exhibits extensive microtubule bundling, due to increased abundance and reduced phosphorylation of the microtubule-associated protein MAP65-1, thus providing a very useful genetic tool to record intrabundle microtubule dynamics at the subdiffraction level. SIM imaging revealed nano-sized defects in microtubule bundling, spatially resolved microtubule branching and release, and finally allowed the quantification of individual microtubules within cortical bundles. Time-lapse SIM imaging allowed the visualization of subdiffraction, short-lived excursions of the microtubule plus end, and dynamic instability behavior of both ends during free, intrabundle, or microtubule-templated microtubule growth and shrinkage. Finally, short, rigid, and nondynamic microtubule bundles in the mpk4 mutant were observed to glide along the parent microtubule in a tip-wise manner. In conclusion, this study demonstrates the potential of SIM for superresolution time-lapse imaging of plant cells, showing unprecedented details accompanying microtubule dynamic organization.
Optimal planning for mitigating the impacts of roads on wildlife
Authors: Polak Tal , Rhodes Jonathan R. , Jones Darryl , Possingham Hugh P.
Published: April 2014

Roads have a significant impact on wildlife world‐wide. Two of the ways to mitigate the impact of roads are to improve connectivity and reduce mortality through fences and wildlife crossings. However, these are expensive actions that will have different effects in different places. Thus, deciding where and how to act in order to achieve the greatest return on investment is crucial. Currently, there are no quantitative approaches to prioritize different road mitigation options.

Here, we use a decision science framework to determine the most cost‐effective combination of actions to mitigate the effects of roads on wildlife under budget constraints. We illustrate our approach using a case study of a threatened koala Phascolarctos cinereus population in south‐east Queensland. We applied a spatially explicit population model to explore the benefits of three kinds of mitigation actions: no action at all and fences with or without crossings, on different road segments.

We explored the trade‐off between expected koala population size, relative to the best outcome, and budget. There is a strong demand for mitigation as the already declining population was reduced even further when no mitigation was employed, while applying the most cost‐effective combination of mitigation actions minimized that decline. Additionally, uncertainty in species attributes (speed of crossing a road and population growth rate) affected population viability but not the decision about which suite of actions (mitigation measures) to take – so our advice on the best action is robust to uncertainty even if the outcome is not. Most importantly, the trade‐off curves between investment and population size are almost linear in this case study. Hence, there is no cheap solution and any reduction in the budget will result in a substantial reduction in expected population size.

Synthesis and applications. This is the first time that the problem of mitigating the effects of roads on wildlife was formulated mathematically and systematically using decision science. Our approach is adaptable to a diversity of species and systems affected by road mortality allowing flexibility for a range of mitigation actions and biological outcomes. Our method will allow managers and decision‐makers to increase the efficiency of mitigation actions.
Satellite remote sensing for applied ecologists: opportunities and challenges
Authors: Pettorelli Nathalie , Laurance William F. , O'Brien Timothy G. , Wegmann Martin , Nagendra Harini , Turner Woody
Published: April 2014

Habitat loss and degradation, overexploitation, climate change and the spread of invasive species are drastically depleting the Earth's biological diversity, leading to detrimental impacts on ecosystem services and human well‐being.

Our ability to monitor the state of biodiversity and the impacts of global environmental change on this natural capital is fundamental to designing effective adaptation and mitigation strategies for preventing further loss of biological diversity. This requires the scientific community to assess spatio‐temporal changes in the distribution of abiotic conditions (e.g. temperature, rainfall) and in the distribution, structure, composition and functioning of ecosystems.

The potential for satellite remote sensing (SRS) to provide key data has been highlighted by many researchers, with SRS offering repeatable, standardized and verifiable information on long‐term trends in biodiversity indicators. SRS permits one to address questions on scales inaccessible to ground‐based methods alone, facilitating the development of an integrated approach to natural resource management, where biodiversity, pressures to biodiversity and consequences of management decisions can all be monitored.

Synthesis and applications. Here, we provide an interdisciplinary perspective on the prospects of satellite remote sensing (SRS) for ecological applications, reviewing established avenues and highlighting new research and technological developments that have a high potential to make a difference in environmental management. We also discuss current barriers to the ecological application of SRS‐based approaches and identify possible ways to overcome some of these limitations.
EnvironmentalDNAsurveillance for invertebrate species: advantages and technical limitations to detect invasive crayfishProcambarus clarkiiin freshwater ponds
Authors: Tréguier Anne , Paillisson Jean‐Marc , Dejean Tony , Valentini Alice , Schlaepfer Martin A. , Roussel Jean‐Marc
Published: April 2014

The introduction of non‐native species is a major threat to biodiversity. While eradication programs of well‐established invaders are costly and hazardous for non‐target species, the early detection of a non‐native species at low density is critical for preventing biological invasions in recipient ecosystems. Recent studies reveal that environmentalDNA(eDNA) is a powerful tool for detecting target species in aquatic ecosystems, but these studies focus mostly on fish and amphibians.

We examine the reliability of using eDNAto detect the presence of an invasive freshwater crustacean species, the red swamp crayfishProcambarus clarkii. Species‐specific primers and probes were designed; their specificity was tested usingin silicoPCRsimulations and against tissues of other crayfish species. Limits of detection and quantification were specified for the targetDNAsequence by means of quantitativePCRamplifications on dilution series of known amount ofP. clarkiiDNA.

The method was applied to water samples collected in 158 ponds in aFrenchNaturePark, and results were compared to a traditional method using food‐baited funnel traps. EnvironmentalDNAhad a better detection efficiency but predominantly led to divergent results compared with the trapping method. While habitat features partly explained the failure of crayfish detection by trapping, detection by eDNAwas problematic at low crayfish abundances. WhenP. clarkiiwas detected, the estimated concentrations of crayfishDNAin water samples were always below the limit of quantification for the targetDNAsequence.

Synthesis and applications. The combination of environmentalDNA(eDNA) and conventional trapping methods is recommended to monitor the invasion byP. clarkiiin small waterbodies such as ponds. However, the risk of mortality for non‐target species, notably amphibians, has to be carefully evaluated before large‐scale deployment of traps. Contrary to fish and amphibians, a low amount of extracellularDNAin water is suspected to be the major limitation for crayfish detection by molecular approaches. Current advancements inPCRtechnology, together with optimization of the water sampling method, promise upcoming developments of eDNAdetection for aquatic invertebrate species.
Response of photosynthesis and respiration to temperature under water deficit in two evergreen Nothofagus species
Authors: Sanhueza Carolina , Bascunan‐Godoy Luisa , Turnbull Matthew H. , Corcuera Luis Julian
Published: April 2014

Respiration and photosynthesis were studied in two Nothofagus species with different drought tolerance in order to evaluate the effect of water deficit on foliar carbon balance and the possible role of the alternative pathway on respiratory adjustment. We propose that under severe water deficit the more drought‐tolerant species N. dombeyi is able to decrease its respiration more than the less drought‐tolerant species N. nitida, thus carbon gain could be maintained when photosynthesis is suppressed by drought. Dark respiration (Rd) and carbon assimilation under saturating light (Asat) were evaluated under seasonal field conditions and during drying and re‐watering cycles under glasshouse. In addition, respiratory pathway changes were evaluated by oxygen isotope fractionation. In the field, N. dombeyi displayed greater light‐saturated photosynthetic capacity than N. nitida, but Rd did not differ between species during summer. In the glasshouse, N. dombeyi displayed an unchanged rate of Rd and increased carbon loss under severe water deficit. Nothofagus nitida displayed a more flexible respiratory response to water deficit, with a lower thermal sensitivity of respiration (decrease in Q10) and a decrease in Rd. This contributed to maintaining leaf carbon balance during the water deficit period. Respiratory electron flow was mainly via the cytochrome pathway for both species and under all treatments, indicating no strong participation of alternative respiration. Our results suggest that under severe water stress, N. dombeyi could be more injured than N. nitida and that the lack of control in the carbon loss under prolonged periods of drought could be limiting for its survival.