bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure and mechanism of the primosome protein DnaT– functional structures for homotrimerization, dissociation of ssDNA from the PriB·ssDNA complex, and formation of the DnaT·ssDNA complex
Authors: Fujiyama Saki , Abe Yoshito , Tani Junya , Urabe Masashi , Sato Kenji , Aramaki Takahiko , Katayama Tsutomu , Ueda Tadashi
Published: September 2014

In Escherichia coli, the primosome plays an essential role in replication restart after dissociation of replisomes at the damaged replication fork. As well as PriA and PriB, DnaT, an ssDNA‐binding protein, is a key member of the primosome. In this study, limited proteolysis indicated that E. coli DnaT was composed of two domains, consistent with the results of recent studies using Klebsiella pneumonia DnaT. We also found that a specific 24‐residue region (Phe42–Asp66) in the N‐terminal domain (1–88) was crucial for DnaT trimerization. Moreover, we determined the structure of the DnaT C‐terminal domain (89–179) by NMR spectroscopy. This domain included three α‐helices and a long flexible C‐terminal tail, similar to the C‐terminal subdomain of the AAA+ ATPase family. The neighboring histidines, His136 and His137, at a position corresponding to the AAA+ sensor II motif, were suggested to form an ssDNA‐binding site. Furthermore, we found that the acidic linker between the two domains had an activity for dissociating ssDNA from the PriB·ssDNA complexes in a manner supported by the conserved acidic residues Asp70 and Glu76. Thus, these findings provide a novel structural basis for understanding the mechanism of DnaT in exposure of ssDNA and reloading of the replicative helicase at the stalled replication fork.

Database

The coordinates used for the ensemble of NMR structures have been deposited in the Protein Data Bank under accession code 2ru8. The NMR data have been deposited in the BioMagResBank (www.bmrb.wisc.edu) under accession number 11549.

Structured digital abstract

DnaT and DnaT bind by nuclear magnetic resonance (View interaction)

DnaT and PriB bind by isothermal titration calorimetry (View interaction)

DnaT and DnaT bind by molecular sieving (View interaction)
Lithium stimulates human bone marrow derived mesenchymal stem cell proliferation through GSK‐3β‐dependent β‐catenin/Wnt pathway activation
Authors: Zhu Zhenzhong , Yin Junhui , Guan Junjie , Hu Bin , Niu Xin , Jin Dongxu , Wang Yang , Zhang Changqing
Published: September 2014

Mesenchymal stem cells (MSCs) are multipotent cells that have been widely used in cell based transplantation therapy. The use of MSCs requires in vitro expansion in order to fulfill their regenerative capacity. Therefore the proliferative ability of MSCs is one of the key factors which determine MSC therapeutic efficacy. In the present study, we showed for the first time that lithium, a well‐known antidepressant, reversibly promoted the proliferation of human bone marrow derived MSCs in vitro. MSCs treated with 5 mm lithium proliferated more rapidly than untreated cells without undergoing apoptosis. Lithium increased the proportion of cells in S phase as well as cyclin D1 expression. Mechanistic studies revealed that these effects were dependent upon the activation of the glycogen synthase kinase 3β (GSK‐3β) mediated canonical Wnt pathway. Lithium induced Ser9 phosphorylation, which results in the inhibition of GSK‐3β activity, β‐catenin accumulation and Wnt pathway activation. Utilizing a specific GSK‐3β inhibitor SB216763 or siRNA‐mediated inhibition of GSK‐3β produced effects similar to those induced by lithium. In contrast, either quercetin, an inhibitor of the β‐catenin/TCF pathway, or siRNA‐mediated knockdown of β‐catenin abolished the proliferative effect of lithium, suggesting that lithium stimulates MSC proliferation via the GSK‐3β‐dependent β‐catenin/Wnt pathway. Collectively, these studies elucidate a novel role of lithium, which may not only provide a simple and effective way to strengthen MSC transplantation therapy efficacy but also shed light on lithium's clinical application for the treatment of certain disorders resulting from β‐catenin/Wnt pathway suppression.
Cyanobacterial bloom termination: the disappearance of Planktothrix rubescens from Lake Bourget (France) after restoration
Authors: Jacquet Stéphan , Kerimoglu Onur , Rimet Frédéric , Paolini Gérard , Anneville Orlane
Published: September 2014

Like many large freshwater ecosystems in Europe, Lake Bourget suffered from eutrophication during the second part of the 20th century and since the 1980s has been partially restored by reductions in nutrient loadings.

Here, we analyse a data set comprised of field measurements of physicochemical and biological variables in Lake Bourget covering the period from 2004 to 2011 and complement this data set with laboratory experiments, to gain an understanding of the changes in phytoplankton community structure during recent years and drivers of these changes.

Between 1995 and 2008, Lake Bourget was characterised by the proliferation of the red‐coloured filamentous and toxic cyanobacterium Planktothrix rubescens, comprising 34.1–52.6% of the total phytoplanktonic biomass between 2004 and 2008.

In 2009, although the contribution of P. rubescens to the total biomass was still considerable (25.3%), it was significantly lower (P < 0.05) compared with previous years. The cyanobacterium disappeared completely during the autumn to winter transition of 2009/2010 and has not been recorded since this time.

Concomitantly, total phytoplanktonic biomass declined sharply and a new phytoplanktonic community occurred consisting predominantly of mixotrophic genera, such as Dinobryon spp., Rhodomonas, Cryptomonas and a variety of different diatoms such as Stephanodiscus, Cyclotella and Fragilaria.

Our findings suggest declines in phosphorus concentration as a key variable in bloom termination, although a number of other factors could also be important, such as temperature‐dependent water column mixing, light availability, zooplankton grazing and seasonal cyanobacterial inoculums.
Breeding in the stable boreal landscape: lake habitat variability drives brood production in the teal (Anas crecca)
Authors: Holopainen Sari , Nummi Petri , Pöysä Hannu
Published: September 2014

Boreal forest lakes are normally considered stable environments, but from a duck's point of view, both resource abundance and habitat quality in the lakes may differ from 1 year to another. Duck species differ in their flexibility to respond to variation in environmental factors, such as habitat quality, habitat variability and weather. Anas crecca, the common teal, has been suggested to be a species that can readily colonise newly formed habitat.

We studied the effect of habitat quality (invertebrate food resources, amount of spring flood, beaver flood abundance, predation pressure), weather (temperature, precipitation, timing of ice break‐up) and pair abundance on breeding success of teal at the landscape scale in Southern Finland. We used 20 years of data (1989–2008) from a study area consisting of 50 lakes. This is typical boreal breeding area for the teal, whose population size is markedly variable. We express breeding success as number of broods in two different age classes.

The number of broods in both age classes was explained well by habitat quality, but different variables seem to operate during different phases of the breeding season. Increases in abundance of breeding pairs and of food led to increased production of younger broods. Habitat factors including food and flood abundance were the most important predictors for older broods, which are the more influential in terms of recruitment. These factors manifested in an age‐specific manner, highlighting the importance of comprehensive breeding time surveys of boreal breeding ducks to understand variation in their recruitment.

Our research underlines the importance of high‐quality habitats for breeding teal populations in the boreal forest landscape. The existence of these habitats depends substantially on human actions, such as managing beaver populations and preserving seasonal pond habitats.
Mortality, movement and behaviour of native mussels during a planned water‐level drawdown in the Upper Mississippi River
Authors: Newton Teresa J. , Zigler Steve J. , Gray Brian R.
Published: September 2014

Managers in the Upper Mississippi River (UMR) are using reductions in the River's water levels during summer to mimic historical water regimes and rehabilitate habitats for vegetation and other species. Concerns for the unintended effects of these actions on mussel populations threatened to halt these projects.

Our objective was to characterise the survival and movement of two mussel species in the UMR associated with a water level drawdown. During 2009 (no drawdown) and 2010 (0.3 m summer drawdown), we glued passive integrated transponder tags to 10 Amblema plicata and 10 Lampsilis cardium at each of 11 sites. Five sites were in shallow areas expected to be minimally affected by the drawdown (reference sites), and six sites were in shallow areas expected to be directly affected by the drawdown (treatment sites). About equal numbers of sites within both the reference and treatment areas had low and high slopes. Tagged mussels were randomly allocated across sites (within years).

Recovery of tagged mussels was >88% in 2009 and 2010. Mortality was similar and low (mean, c. 5% in both species) among reference sites but was variable and relatively high (means, c. 27% in L. cardium and c. 52% in A. plicata) among treatment sites; variation in mortality among treatment sites appeared related to slope.

The study found evidence of drawdown associations with net horizontal movements in A. plicata but not L. cardium. Weekly horizontal movements in both species were significantly correlated with changes in water elevation. We observed significant slope associations related to the drawdown for mortality and net horizontal movement in A. plicata.

There were strong species‐specific differences in the effects of the drawdown on mortality, vertical movement and horizontal movement. These results suggest that A. plicata responded to the drawdown by vertical movement into the substratum, whereas L. cardium responded by horizontal movement to deeper water. No directionality of movement was observed in either species.

Collectively, these data suggest that drawdowns can influence the mortality, movement and behaviour of mussels in the UMR. However, more information on spatial and temporal distributions of mussels is needed to better understand the magnitude of these effects. Results from this study are being used by resource managers to better evaluate the effects of this management tool on native mussel assemblages.
Effects of nutrients and warming on Planktothrix dynamics and diversity: a palaeolimnological view based on sedimentary DNA and RNA
Authors: Savichtcheva Olga , Debroas Didier , Perga Marie Elodie , Arnaud Fabien , Villar Clément , Lyautey Emilie , Kirkham Amy , Chardon Cécile , Alric Benjamin , Domaizon Isabelle
Published: September 2014

Decennial changes in Planktothrix rubescens diversity and dynamics were reconstructed by applying molecular tools to analyse DNA and RNA extracted from lake sediments. The sediments studied were sampled from a deep peri‐alpine lake that has experienced both dramatic shifts in trophic conditions and large‐scale climatic changes. Palaeolimnological proxies were combined with statistical modelling to investigate the relative influence of phosphorus concentrations and temperature changes on the extent of Planktothrix blooms over the last century.

Phylogenetic analysis revealed that the overall composition of the cyanobacterial community changed over the transition from oligotrophic to eutrophic conditions. When the relative abundance of Planktothrix decreased in the 1970s, concomitant with eutrophication, total cyanobacterial abundance remained high and more Anabaena and Microcystis sequences were detected. In spite of such drastic environmental changes, the lake provided a constant niche for one particular Planktothrix species, which was consistently present from the 1920s to the present day.

Phosphorus concentration was found to be the dominant driver of the relative abundance of P. rubescens, with the highest abundances observed during mesotrophic conditions. The relative role of climate was nutrient‐dependent, with warmer springs having a positive effect on P. rubescens abundance only during mesotrophic periods.

Overall, this study confirms that analysis of genetic signatures preserved in sediment archives allows assessment of key palaeoenvironmental indicator species that have no diagnostic microscopic cellular features in the sediment record. In the case of cyanobacteria, palaeogenetics offer unique opportunities to anticipate how future climate change might affect the response of P. rubescens to phosphorus concentration.
Reduced investment in sex as a cost of inducible defence inBrachionus calyciflorus(Rotifera)
Authors: Yin Xu Wang , Zhou Yan Chun , Li Xiao Chun , Li Wen Xiang
Published: September 2014

Inducible defences reduce the probability of prey being killed by their predators. However, these defences are often accompanied by costs. Most studies associated with aquatic communities have focused on the effects of inducible defences on the growth and reproduction of prey species, while their effects on sex investment remain unclear.

Brachionus calyciflorusis a common freshwater rotifer that develops a defensive morphology in response to the kairomones released by the predatory rotiferAsplanchna. Some studies have reported that no detectable cost, such as decreased reproductive output, is associated with the spines inB. calyciflorus. Thus, we studied the sex investment (i.e. production of mictic offspring and resting eggs) ofB. calycifloruspopulations at threeAsplanchnakairomone concentrations (0, 10, and 100 Asplanchna L−1) and two food levels (1 and 12 mg C L−1) to evaluate the sex cost of inducible defences. We also evaluated the crowding threshold required to trigger sex investment (i.e. lowest population density at which mictic female is produced) inB. calyciflorusunder different kairomone and food treatments.

Results showed that (i) theB. calycifloruspopulation exposed to kairomones produced offspring with elongated posterolateral spines; (ii) the production of mictic offspring and resting eggs decreased in theB. calycifloruspopulation exposed to kairomones, suggesting an investment trade‐off exists between inducible defence and sex investment; (iii) the decrease in sex investment was higher at the high kairomone concentration than at the low kairomone concentration; (iv) the decrease of sex investment was higher at the low food level than at the high food level; and (v) the crowding threshold of theB. calycifloruspopulation increased upon exposure to kairomones.

The results of this study suggest that the decreased sex investment in defendedB. calyciflorusis a form of defence cost. Our findings add to our understanding of the effect of predation on the ecology and evolution of phenotypic plasticity in rotifers.
Normal stress‐induced permeability hysteresis of a fracture in a granite cylinder
Authors: Selvadurai A. P. S.
Published: September 2014

The paper examines the influence of axial stress‐induced closure of a fracture on its permeability. The experiments were conducted on a cylinder of Barre Granite measuring 457 mm in diameter and 510 mm in height, containing a central cylindrical cavity of diameter 75 mm. Radial flow hydraulic pulse tests were conducted in a previous research investigation (Selvadurai et al., PAGEOPH, 2005) to determine the permeability characteristics of the intact granite. In the continuation of the research, a fracture was introduced in the cylinder with its nominal plane normal to the axis of the cylinder. Axial compressive stress was applied normal to the plane of the fracture. An increase in the compressive normal stress acting on the fracture caused a reduction in the aperture of the fracture, which resulted in the reduction in its permeability. Steady state radial flow tests were conducted on the fractured axially stressed sample to determine the variation of fracture permeability with axial normal stress. The analytical developments also take into account flow through the matrix region as the normal stress increases. The results of the experimental investigations indicate that the complete stress relief of a fracture previously subjected to a normal stress of 7.5 MPa can result in a permeability increase of approximately three orders of magnitude. These findings are relevant to shallow depth geotechnical construction activities where enhanced fluid flow can be activated by stress relief. As the fracture aperture closes with high normal stress, the flow through the matrix can be appreciable and if this factor is not taken into consideration the interpretation of fracture permeability can be open to error. This factor can be of interest to the interpretation of permeability of fractures in deep crustal settings where the stresses acting normal to the fracture surface can inhibit flow in the fracture.
Expression of haem oxygenase‐1 correlates with tumour aggressiveness and BRAFV600E expression in thyroid cancer
Authors: Wang Tao‐Yeuan , Liu Chien‐Liang , Chen Ming‐Jen , Lee Jie‐Jen , Pun Pou Chu , Cheng Shih‐Ping
Published: September 2014

Aims

Haem oxygenase‐1 (HO‐1) is an inducible enzyme that participates in haem degradation. Recent studies have indicated that HO‐1 activation may play a role in tumour development and progression. The aim of this study was to evaluate the expression of HO‐1 in thyroid cancer and its clinicopathological significance.

Methods and results

We observed up‐regulation of HO‐1 in papillary thyroid tumours in comparison with normal thyroid tissue. Immunohistochemical analysis revealed that 48% of papillary cancers and 36% of follicular cancers, but none of normal thyroid tissues, were positive for HO‐1 expression. Among 129 differentiated thyroid cancers, HO‐1 expression was associated with patient age (P = 0.001), TNM stage (P = 0.001), and Mayo Clinic metastasis, patient age, completeness of resection, local invasion and tumour size score (P = 0.001). BRAFV600E expression was evaluated immunohistochemically and validated by Sanger sequencing. There was a strong association between HO‐1 and BRAFV600E expression in papillary cancers (P = 0.002).

Conclusions

Overexpression of HO‐1 in a subset of thyroid cancers is associated with tumour aggressiveness and BRAFV600E expression. HO‐1 might have a potential role in prognosis and targeted treatment in patients with thyroid cancer.
Current concepts of colorectal cancer resection pathology
Authors: Nagtegaal Iris D
Published: September 2014

The discussion of pathology results is one of the important items in the multidisciplinary meeting. These results describe not only the adequacy of earlier treatments (neoadjuvant therapy, surgery), but guide subsequent treatment decisions by providing staging information and additional prognostic and predictive factors. In the era of next‐generation sequencing, every so often the emphasis is put on the molecular background of tumours, but the information that can be retrieved from the resection specimen remains essential for optimal patient care. In the current review the different surgical approaches will be described, together with the relevant macroscopic evaluations. Microscopic features will be addressed, giving an overview that is aimed at optimal information exchange in the multidisciplinary meeting. Finally, special requirements for reporting local excisions and specimen after neoadjuvant therapy will be discussed.
A study of the interleukin‐1 gene cluster polymorphisms and inflammatory external root resorption in replanted permanent teeth
Authors: Bastos J. V. , Côrtes M. I. S. , Silva J. F. C. , Goulart E. M. A. , Colosimo E. A. , Gomez R. S. , Dutra W. O.
Published: September 2014

Aim

To investigate whether single nucleotide polymorphisms (SNPs) within the interleukin‐1 gene cluster (IL1) are associated with the occurrence and severity of inflammatory external root resorption (IERR) after replantation of avulsed permanent teeth.

Methodology

Indexes ofIERRwere radiographically assessed in 182 mature replanted permanent teeth from 146 patients at the onset of endodontic therapy.DNAwas extracted from buccal mucosa cells and genotyped using TaqMan probes‐based assays for theSNPsIL1A‐889C/T (rs 180058),IL1B+3954C/T (rs1143634) andIL1RN+2018C/T (rs419598). Teeth were grouped into two categories:IERRabsent to mild (indexes ≤4) and moderate to severeIERR(indexes >4). Genetic variations in theIL1gene cluster were tested for their effect on the occurrence and extension ofIERRusing theGEEmodel (generalized estimation equation). Patient's age at the moment of injury, timing of pulpectomy, extra‐alveolar period and storage condition of the avulsed teeth was included as possible confounders.

Results

No association was found betweenSNPsIL1A‐889C/T,IL1B+3954C/T (rs1143634) andIL1RN+2018C/T (rs419598) andIERRindexes. Timing of pulpectomy (OR3.5IC95% 2.0–6.2P < 0.001) and patient's age at the moment of trauma (OR0.29IC95% 0.12–0.67P = 0.004) significantly affected the risk of developing severeIERR.

Conclusions

While timing of pulpectomy and patient's age at the moment of trauma were confirmed as important risk factors,SNPs within theIL1gene cluster did not affect the susceptibility forIERRafter replantation of permanent teeth.
Triptolide inhibits transforming growth factor‐β1‐induced proliferation and migration of rat airway smooth muscle cells by suppressing nuclear factor‐κB but not extracellular signal‐regulated kinase 1/2
Authors: Chen Ming , Shi Jian‐Ting , Lv Zhi‐Qiang , Huang Lin‐Jie , Lin Xiao‐Ling , Zhang Wei , Liang Rui‐Yun , Li Yi‐Qun , Jiang Shan‐Ping
Published: September 2014

Airway remodelling contributes to increased mortality in asthma. We have reported that triptolide can inhibit airway remodelling in a mouse asthma model. In this study, we aimed to investigate the effect of triptolide on proliferation and migration of airway smooth muscle cells (ASMC), and the possible mechanism. Rat ASMC were cultured and synchronized, then pre‐treated with different concentrations of triptolide before being stimulated by transforming growth factor‐β1 (TGF‐β1). Cell proliferation was evaluated by cell counting and MTT assay. Flow cytometry was used to study the influence of triptolide on the cell cycle. Migration was measured by Transwell analysis. Signal proteins [nuclear factor‐κB (NF‐κB) p65 and extracellular signal‐regulated kinase 1/2 (ERK1/2)] were detected by Western blotting. A lactate dehydrogenase releasing test and flow cytometry analysis of apoptosis were also performed to explore the potential cytotoxic or pro‐apoptotic effects of triptolide. Triptolide significantly inhibited TGF‐β1‐induced ASMC proliferation and migration (P < 0·05). The cell cycle was dose‐dependently blocked at G1/S‐interphase by triptolide. Western blotting analysis showed that TGF‐β1‐induced NF‐κB p65 phosphorylation was inhibited by triptolide pre‐treatment, but ERK1/2 was not affected. No cytotoxic or pro‐apoptotic effects were detected under the concentration of triptolide that was used. Triptolide may function as an inhibitor of asthma airway remodelling by suppressing ASMC proliferation and migration through inactivation of the NF‐κB pathway.
Diaspora Institutions and Diaspora Governance
Authors: Gamlen Alan
Published: September 2014

Why do governments form institutions devoted to emigrants and their descendants in the diaspora? Such institutions have become a regular feature of political life in many parts of the world: Over half all United Nations Member States now have one. Diaspora institutions merit research because they connect new developments in the global governance of migration with new patterns of national and transnational sovereignty and citizenship, and new ways of constructing individual identity in relation to new collectivities. But these institutions are generally overlooked. Migration policy is still understood as immigration policy, and research on diaspora institutions has been fragmented, case-study dominated, and largely descriptive. In this article, I review and extend the relevant theoretical literature and highlight empirical research priorities. I argue that existing studies focus too exclusively on national-level interests and ideas to explain how individual states tap diaspora resources and embrace these groups within the nation-state. However, these approaches cannot explain the global spread of diaspora institutions. This, I argue, requires a comparative approach and greater attention to the role of efforts to create a coherent but decentralized system of global governance in the area of international migration.
Reconsidering Migration and Class
Authors: Van Hear Nicholas
Published: September 2014

While once a mainstay of social science, class has lately been eclipsed in much of migration studies by consideration of other forms of social difference, affinity, and allegiance such as ethnicity, gender, generation, and lately religion. This article puts the case for renewing attention on the part class plays in shaping migration – particularly who is able to move and to where. It argues that the form of migration and ultimately its outcomes are shaped by the resources that would-be migrants can muster and that in turn the capacity to mobilize such resources is largely determined by socio-economic background or class. Drawing on Bourdieu, class can be conceived in terms of the disposal of different forms of capital – economic, social, and cultural. Having access to combinations of such capital shapes the routes and channels migrants can follow, the destinations they can reach, and their life chances after migration. The article first reflects briefly on ideas of class in social science and sketches treatment of mobility in the migration literature, before considering the ways in which class, mobility, and immobility shape each other. The article concludes by considering the interplay between migration, class, and collective action among those who move and those who stay, against the background of broader currents of social change and transformation.
Migration Infrastructure
Authors: Xiang Biao , Lindquist Johan
Published: September 2014

Based on the authors’ long-term field research on low-skilled labor migration from China and Indonesia, this article establishes that more than ever labor migration is intensively mediated. Migration infrastructure – the systematically interlinked technologies, institutions, and actors that facilitate and condition mobility – serves as a concept to unpack the process of mediation. Migration can be more clearly conceptualized through a focus on infrastructure rather than on state policies, the labor market, or migrant social networks alone. The article also points to a trend of “infrastructural involution,” in which the interplay between different dimensions of migration infrastructure make it self-perpetuating and self-serving, and impedes rather than enhances people's migratory capability. This explains why labor migration has become both more accessible and more cumbersome in many parts of Asia since the late 1990s. The notion of migration infrastructure calls for research that is less fixated on migration as behavior or migrants as the primary subject, and more concerned with broader societal transformations.
The International Migration Review at 50: Reflecting on Half a Century of International Migration Research and Looking Ahead
Authors: Lee Jennifer , Carling Jørgen , Orrenius Pia
Published: September 2014

When the International Migration Review was established half a century ago, international migration was a peripheral area of research, and migration issues were far less prominent on policy agendas than they are today. This essay introduces the 50th Anniversary Issue of the International Migration Review and begins by identifying seven main areas of change in migration research and migration trends during the journal's lifetime. Subsequently, we examine changes in the geographical distribution of authorship of IMR articles. We also explore the IMR's current positioning in the scientific landscape by analyzing citation relationships with other journals. The ten articles that make up the body of the special issue seek to advance the research frontier on international migration, covering diverse areas of the IMR's thematic scope. We account for how the papers were selected and present each one. In the final section of the article, we look ahead and suggest new frontiers in international migration research. Among the research themes that we foresee as increasingly important are connections between migration and inequality, and the growth of migration flows that are driven by humanitarian crises, but not accommodated by the international refugee regime.
The effect of parity on morphological evolution among phrynosomatid lizards
Authors: Oufiero C. E. , Gartner G. E. A.
Published: September 2014

The shift from egg laying to live‐bearing is one of the most well‐studied transitions in evolutionary biology. Few studies, however, have assessed the effect of this transition on morphological evolution. Here, we evaluated the effect of reproductive mode on the morphological evolution of 10 traits, among 108 species of phrynosomatid lizards. We assess whether the requirement for passing shelled eggs through the pelvic girdle has led to morphological constraints in oviparous species and whether long gestation times in viviparous species have led to constraints in locomotor morphology. We fit models to the data that vary both in their tempo (strength and rate of selection) and mode of evolution (Brownian or Ornstein‐Uhlenbeck) and estimates of trait optima. We found that most traits are best fit by a generalized multipeak OU model, suggesting differing trait optima for viviparous vs. oviparous species. Additionally, rates (σ2) of both pelvic girdle and forelimb trait evolution varied with parity; viviparous species had higher rates. Hindlimb traits, however, exhibited no difference in σ2 between parity modes. In a functional context, our results suggest that the passage of shelled eggs constrains the morphology of the pelvic girdle, but we found no evidence of morphological constraint of the locomotor apparatus in viviparous species. Our results are consistent with recent lineage diversification analyses, leading to the conclusion that transitions to viviparity increase both lineage and morphological diversification.
Grandparental effects in marine sticklebacks: transgenerational plasticity across multiple generations
Authors: Shama L. N. S. , Wegner K. M.
Published: September 2014

Nongenetic inheritance mechanisms such as transgenerational plasticity (TGP) can buffer populations against rapid environmental change such as ocean warming. Yet, little is known about how long these effects persist and whether they are cumulative over generations. Here, we tested for adaptiveTGPin response to simulated ocean warming across parental and grandparental generations of marine sticklebacks. Grandparents were acclimated for two months during reproductive conditioning, whereas parents experienced developmental acclimation, allowing us to compare the fitness consequences of short‐term vs. prolonged exposure to elevated temperature across multiple generations. We found that reproductive output of F1 adults was primarily determined by maternal developmental temperature, but carry‐over effects from grandparental acclimation environments resulted in cumulative negative effects of elevated temperature on hatching success. In very early stages of growth, F2 offspring reached larger sizes in their respective paternal and grandparental environment down the paternal line, suggesting that other factors than just the paternal genome may be transferred between generations. In later growth stages, maternal and maternal granddam environments strongly influenced offspring body size, but in opposing directions, indicating that the mechanism(s) underlying the transfer of environmental information may have differed between acute and developmental acclimation experienced by the two generations. Taken together, our results suggest that the fitness consequences of parental and grandparentalTGPare highly context dependent, but will play an important role in mediating some of the impacts of rapid climate change in this system.
Oh sister, where art thou? Spatial population structure and the evolution of an altruistic defence trait
Authors: Pamminger T. , Foitzik S. , Metzler D. , Pennings P. S.
Published: September 2014

The evolution of parasite virulence and host defences is affected by population structure. This effect has been confirmed in studies focusing on large spatial scales, whereas the importance of local structure is not well understood. Slavemaking ants are social parasites that exploit workers of another species to rear their offspring. Enslaved workers of the host species Temnothorax longispinosus have been found to exhibit an effective post‐enslavement defence behaviour: enslaved workers were observed killing a large proportion of the parasites’ offspring. As enslaved workers do not reproduce, they gain no direct fitness benefit from this ‘rebellion’ behaviour. However, there may be an indirect benefit: neighbouring host nests that are related to ‘rebel’ nests can benefit from a reduced raiding pressure, as a result of the reduction in parasite nest size due to the enslaved workers’ killing behaviour. We use a simple mathematical model to examine whether the small‐scale population structure of the host species could explain the evolution of this potentially altruistic defence trait against slavemaking ants. We find that this is the case if enslaved host workers are related to nearby host nests. In a population genetic study, we confirm that enslaved workers are, indeed, more closely related to host nests within the raiding range of their resident slavemaker nest, than to host nests outside the raiding range. This small‐scale population structure seems to be a result of polydomy (e.g. the occupation of several nests in close proximity by a single colony) and could have enabled the evolution of ‘rebellion’ by kin selection.
Household measures for river flood risk reduction in the Czech Republic
Authors: Duží B. , Vikhrov D. , Kelman I. , Stojanov R. , Juřička D.
Published: September 2014

Interviews with 304 households were used to determine flood risk reduction measures adopted in the case study of the Becva River in the Czech Republic. Uptake of measures was low, irrespective of experience with floods. Financial cost seemed to be a barrier towards implementation, but more work is needed to understand the combination of factors limiting adoption of household flood risk reduction measures. Regression analysis indicated that socio‐demographic factors play an important role in household decision making. More men and more children in a household support the adoption of measures. Perception of living in a flood risk zone, rather than actual experience of flooding, also positively influenced probability of adopting some measures. When a house is elevated up from ground level by 1 metre or more, the likelihood of taking further measures decreased by 20%. Further investigation of these factors and why, not just how, they influence household choices would support flood risk reduction measures, especially under a changing climate.
Novel personalized therapies for cystic fibrosis: treating the basic defect in all patients
Authors: Amaral M. D.
Published: September 2014

Cystic fibrosis (CF) is the most common genetic life‐shortening condition in Caucasians. Despite being a multi‐organ disease, CF is classically diagnosed by symptoms of acute/chronic respiratory disease, with persistent pulmonary infections and mucus plugging of the airways and failure to thrive. These multiple symptoms originate from dysfunction of the CF transmembrane conductance regulator (CFTR) protein, a channel that mediates anion transport across epithelia. Indeed, establishment of a definite CF diagnosis requires proof of CFTR dysfunction, commonly through the so‐called sweat Cl− test. Many drug therapies, including mucolytics and antibiotics, aim to alleviate the symptoms of CF lung disease. However, new therapies to modulate defective CFTR, the basic defect underlying CF, have started to reach the clinic, and several others are in development or in clinical trials. The novelty of these therapies is that, besides targeting the basic defect underlying CF, they are mutation specific. Indeed, even this monogenic disease is influenced by a large number of different genes and biological pathways as well as by environmental factors that are difficult to assess. Accordingly, every person with CF is unique and so functional assessment of patients' tissues ex vivo is key for diagnosing and predicting the severity of this disease. Of note, such assessment will also be crucial to assess drug responses, in order to effectively treat all CF patients. It is not because it is a monogenic disorder that personalized treatment for CF is much easier than for complex disorders.
Gene loss in plants: Evidence from genome‐wide phylogenetic analysis of thiamine pyrophosphate‐dependent enzymes
Authors: Tian Xin‐Min , Wang Peng , Hu Wen‐Bin , Gao Da‐Hai , Li Qiong
Published: September 2014

Thiamine pyrophosphate (TPP)‐dependent enzymes are present in all domains of life, which share a cofactor with TPP. However, a comprehensive analysis of TPP‐dependent enzymes from sequenced genomes has not been reported and little is known about the evolutionary dynamics of this gene family in plants. In this study, the evolutionary relationships of the TPP‐dependent enzymes were investigated by using a comprehensive genome‐wide phylogenetic analysis. A total of 103 plant TPP‐dependent enzyme sequences were identified in 16 plant species. Phylogenetic analyses suggest that these plant TPP‐dependent genes fell into three major groups, acetolactate synthase, pyruvate dehydrogenase, and 2‐hydroxyphytanoyl‐CoA lyase. Our results showed fewer TPP‐dependent genes in plants than that in other living organisms, with many types of genes lost during evolution possibly because they do not largely influence plant function. Within the plant kingdom, seed plants have more TPP genes compared to non‐seed basal plants, which probably imply that seed plants developed more TPP genes to adapt to their environment. The present study provides important information for understanding the evolution and function of the TPP‐dependent gene family in plants.
Interferon‐free treatment of chronic hepatitis C with faldaprevir, deleobuvir and ribavirin: SOUND‐C3, a Phase 2b study
Authors: Zeuzem Stefan , Dufour Jean‐François , Buti Maria , Soriano Vicente , Buynak Robert J. , Mantry Parvez , Taunk Jawahar , Stern Jerry O. , Vinisko Richard , Gallivan John‐Paul , Böcher Wulf , Mensa Federico J. ,   the SOUND‐C3 study group
Published: September 2014

Background & Aims

The safety and efficacy of the interferon‐free combination of faldaprevir (NS3/A4 protease inhibitor), deleobuvir (BI 207127, non‐nucleoside polymerase inhibitor), and ribavirin in treatment‐naïve patients chronically infected with HCV genotype‐1 was explored.

Methods

SOUND‐C3 was a multicenter, open‐label Phase 2b study. Treatment‐naïve patients chronically infected with HCV genotype‐1a (IL28B CC genotype only; n = 12) and genotype‐1b (n = 20) were assigned to 16 weeks of treatment with faldaprevir 120 mg once daily, deleobuvir 600 mg twice daily, and weight‐based ribavirin. Patients with compensated liver disease, including cirrhosis, were eligible for inclusion in this study. The primary endpoint was sustained virological response 12 weeks after completion of therapy.

Results

Sustained virological response rates 12 weeks after completion of therapy were 17% and 95% in patients infected with HCV genotype‐1a and genotype‐1b respectively. All four patients with cirrhosis achieved sustained virological response 12 weeks after completion of therapy. The most frequently reported adverse events of at least moderate intensity were anaemia (16%), nausea, vomiting and fatigue (9% each). Three (9%) patients discontinued because of adverse events.

Conclusions

The interferon‐free regimen of faldaprevir, deleobuvir and ribavirin was efficacious in patients infected with genotype‐1b and generally well tolerated.
Stark sexual display divergence among jumping spider populations in the face of gene flow
Authors: Blackburn Gwylim S. , Maddison Wayne P.
Published: September 2014

Gene flow can inhibit evolutionary divergence by eroding genetic differences between populations. A current aim in speciation research is to identify conditions in which selection overcomes this process. We focused on a state of limited differentiation, asking whether selection enables divergence with gene flow in a set of Habronattus americanus jumping spider populations that exhibit three distinct male sexual display morphs. We found that each population is at high frequency or fixed for a single morph. These strong phenotypic differences contrast with low divergence at 210 AFLP markers, suggesting selection has driven or maintains morph divergence. Coinciding patterns of isolation by distance and ‘isolation by phenotype’ (i.e. increased genetic divergence among phenotypically contrasting populations) across the study area support several alternative demographic hypotheses for display divergence, each of which entails gene flow. Display‐associated structure appears broadly distributed across the genome and the markers producing this pattern do not stand out from background levels of differentiation. Overall, the results suggest selection can promote stark sexual display divergence in the face of gene flow among closely related populations.
Crossing to safety: dispersal, colonization and mate choice in evolutionarily distinct populations ofSteller sea lions,Eumetopias jubatus
Authors: O'Corry‐Crowe Greg , Gelatt Tom , Rea Lorrie , Bonin Carolina , Rehberg Michael
Published: September 2014

Population growth typically involves range expansion and establishment of new breeding sites, while the opposite occurs during declines. Although density dependence is widely invoked in theoretical studies of emigration and colonization in expanding populations, few empirical studies have documented the mechanisms. Still fewer have documented the direction and mechanisms of individual transfer in declining populations. Here, we screen large numbers of pups sampled on their natal rookeries for variation in mtDNA(n = 1106) and 16 microsatellite loci (n = 588) and show that new Steller sea lion breeding sites did not follow the typical paradigm and were instead colonized by sea lions from both a declining (Endangered) population and an increasing population. Dispersing individuals colonized rookeries in the distributional hiatus between two evolutionarily distinct ( = 0.222, = 0.053,K = 2) metapopulations recently described as separate subspecies. Hardy–Weinberg, mixed‐stock and relatedness analysis revealed levels of interbreeding on the new rookeries that exclude (i) assortative mating among eastern and western forms, and (ii) inbreeding avoidance as primary motivations for dispersal. Positive and negative density dependence is implicated in both cases of individual transfer. Migration distance limits, and conspecific attraction and performance likely influenced the sequence of rookery colonizations. This study demonstrates that resource limitation may trigger an exodus of breeding animals from declining populations, with substantial impacts on distribution and patterns of genetic variation. It also revealed that this event is rare because colonists dispersed across an evolutionary boundary, suggesting that the causative factors behind recent declines are unusual or of larger magnitude than normally occur.
Lipoastrocytoma: A rare case report and review of literature
Authors: Sharma Divya , Khurana Nita
Published: September 2014

Lipoastrocytoma is an extremely rare tumor, with only a few cases described. We report a case of a low‐grade astrocytoma occupying the right cortical lobe in the parafalcine location. The patient was admitted with headache, vomiting and altered sensorium for duration of 1 year. MRI revealed a large heterogeneous enhancing mass in the right fronto‐parieto‐temporal lobe with intratumoral fat along with cystic changes and calcification (correlated with CT) showing mass effect in the third ventricle. A gross total excision of the tumor was performed. Histologically, the tumor showed glial cells that contained lipid droplets coalescing into a single large droplet, similar in appeareance to adipocytes. Immunohistocemically, tumor cells strongly expressed GFAP and S‐100 protein. Ki‐67 labelling index was low. The patient remained in good neurological condition at 3 months follow‐up. This case represents a rare variant of low‐grade astrocytoma that is designated as lipoastrocytoma.
Quality of life in women with infertility via the FertiQoL and the Hospital Anxiety and Depression Scales
Authors: Kahyaoglu Sut Hatice , Balkanli Kaplan Petek
Published: September 2014

The aim of this study was to examine the relationships between quality of life, anxiety, and depression in female patients with infertility. This was a cross‐sectional study with 89 women with infertility. Patients completed a questionnaire that included demographic data, the FertiQoL scale, and the Hospital Anxiety and Depression Scale. The average total FertiQoL score was 66.0 ± 14.5. There were negative correlations between the treatment and core FertiQoL scores and the Hospital Anxiety‐Depression subscale scores. The attempted conception duration was negatively correlated with the total and core (emotional, mind‐body, and social subscales) scores of the FertiQoL. The number of in vitro fertilizations was negatively correlated with the total, core (mind‐body subscale), and treatment (tolerability subscale) scores of the FertiQoL. In conclusion, infertility significantly reduces quality of life in women by increasing their anxiety and depression levels. Thus, healthcare professionals should consider quality of life with a holistic approach when examining and treating women with infertility.
Extensive cross‐environment fitness variation lies along few axes of genetic variation in the model alga, Chlamydomonas reinhardtii
Authors: Malcom Jacob W. , Hernandez Kyle M. , Likos Raquel , Wayne Tierney , Leibold Mathew A. , Juenger Thomas E.
Published: September 2014

Variation is essential to ecological and evolutionary dynamics, but genetic variation of quantitative traits may be concentrated in a limited number of dimensions, constraining ecoevolutionary dynamics. We describe high‐dimension variation in natural accessions of the model alga, Chlamydomonas reinhardtii, and test the hypothesis that extensive fitness variation across 30 environments is constrained to a small number of axes.

We used high‐throughput phenotyping to investigate morphological, fitness, and genotype × environment (G × E) variation in 18 natural C. reinhardtii accessions in 30 environments.

The organismal phenotypes of cell cycle, cell size, and phototactic behavior exhibited substantial genetic variation between lines, and we found up to 74‐fold fitness variation across accessions and environments. Approximately 47% of the extensive G × E variation is accounted for by the first two principal components (PCs) of the G‐matrix corresponding to covariation in metals response, nitrogen availability, or salt and nutrient response.

The natural variation of C. reinhardtii accessions supports the hypothesis that, despite abundant genetic variation across single environments, the species' adaptive response should be constrained along few major axes of selection. These results highlight the utility of natural accessions for integrating ecoevolutionary and genetic research.