bluuebunny/crossref_metadata_2025 huggingface dataset:
Palaeo‐islands as refugia and sources of genetic diversity within volcanic archipelagos: the case of the widespread endemic Canarina canariensis (Campanulaceae)
Authors: Mairal M. , Sanmartín I. , Aldasoro J. J. , Culshaw V. , Manolopoulou I. , Alarcón M.
Published: June 2015

Geographical isolation by oceanic barriers and climatic stability has been postulated as some of the main factors driving diversification within volcanic archipelagos. However, few studies have focused on the effect that catastrophic volcanic events have had on patterns of within‐island differentiation in geological time. This study employed data from the chloroplast (cpDNA haplotypes) and the nuclear (AFLPs) genomes to examine the patterns of genetic variation in Canarina canariensis, an iconic plant species associated with the endemic laurel forest of the Canary Islands. We found a strong geographical population structure, with a first divergence around 0.8 Ma that has Tenerife as its central axis and divides Canarian populations into eastern and western clades. Genetic diversity was greatest in the geologically stable ‘palaeo‐islands’ of Anaga, Teno and Roque del Conde; these areas were also inferred as the ancestral location of migrant alleles towards other disturbed areas within Tenerife or the nearby islands using a Bayesian approach to phylogeographical clustering. Oceanic barriers, in contrast, appear to have played a lesser role in structuring genetic variation, with intra‐island levels of genetic diversity larger than those between‐islands. We argue that volcanic eruptions and landslides after the merging of the palaeo‐islands 3.5 Ma played key roles in generating genetic boundaries within Tenerife, with the palaeo‐islands acting as refugia against extinction, and as cradles and sources of genetic diversity to other areas within the archipelago.
Real Exchange Rate and Economic Growth: New Empirical Evidence
Authors: Missio Fabrício J. , Jayme Frederico G. , Britto Gustavo , Luis Oreiro José
Published: June 2015

The article empirically analyses the relationship between real exchange rate (RER) and growth rate of output. We first estimate the effect of the index of RER undervaluation on the rate of output growth in two samples of countries from 1978 to 2007. Our contribution is the use of a different dataset that increases the number of countries in the sample, as well as the number of available control variables. In doing so, the article adds to the literature by applying a method that allows for the control of income levels (quantile regressions). So, we present new findings on a non‐linear relationship the RER‐growth nexus. We conclude that maintaining a competitive level of RER has positive effects on growth rate.
Quantitative Imaging In Vivo of Functioning Lymphatic Vessels Around Human Melanoma and Benign Nevi
Authors: Akhras Victoria , Ramakrishnan Rathi , Stanton Anthony W.B. , Levick John R. , Cook Martin G. , Chong Heung , Mortimer Peter S.
Published: June 2015

Objectives

The density of functioning human lymphatics in vivo and of immunohistochemically defined lymphatics was quantified around melanomas, benign nevi, and matched normal skin, to assess the current lymphangiogenesis paradigm. We investigated whether histological and functioning density increased around melanomas compared with benign nevi or matched skin; whether functioning and histological density increased similarly; and whether larger increases occurred around metastatic melanomas.

Methods

Functioning density was quantified in vivo as the total amount of human dermal microlymphatics taking up fluorescent marker injected at the lesion margin. After tissue excision, perilesion histological density was quantified using podoplanin marker D2‐40.

Results

Histological density was raised similarly around metastasising and non‐metastasising melanomas compared with normal skin (+71%, p < 0.0001, n = 32); but was also raised significantly around benign nevi (+17%, p = 0.03, n = 20). In contrast, functioning lymphatic density was substantially reduced around the margins of melanomas (both metastasising and non‐metastasising) compared with benign nevi (by 65%, p = 0.02) or normal skin (by 53%, p = 0.0014).

Conclusions

Raised perilesion histological lymphatic density is not unique to melanoma but occurs also around benign nevi. The findings indicated that the number of functioning lateral lymphatics around human melanomas in vivo but not benign nevi is reduced, despite histologically increased numbers of lymphatics.
RNA degradosomes in bacteria and chloroplasts: classification, distribution and evolution of RNase E homologs
Authors: Aït‐Bara Soraya , Carpousis Agamemnon J.
Published: June 2015

Ribonuclease E (RNase E) of Escherichia coli, which is the founding member of a widespread family of proteins in bacteria and chloroplasts, is a fascinating enzyme that still has not revealed all its secrets. RNase E is an essential single‐strand specific endoribonuclease that is involved in the processing and degradation of nearly every transcript in E. coli. A striking enzymatic property is a preference for substrates with a 5′ monophosphate end although recent work explains how RNase E can overcome the protection afforded by the 5′ triphosphate end of a primary transcript. Other features of E. coli RNase E include its interaction with enzymes involved in RNA degradation to form the multienzyme RNA degradosome and its localization to the inner cytoplasmic membrane. The N‐terminal catalytic core of the RNase E protomer associates to form a tetrameric holoenzyme. Each RNase E protomer has a large C‐terminal intrinsically disordered (ID) noncatalytic region that contains sites for interactions with protein components of the RNA degradosome as well as RNA and phospholipid bilayers. In this review, RNase E homologs have been classified into five types based on their primary structure. A recent analysis has shown that type I RNase E in the γ‐proteobacteria forms an orthologous group of proteins that has been inherited vertically. The RNase E catalytic core and a large ID noncatalytic region containing an RNA binding motif and a membrane targeting sequence are universally conserved features of these orthologs. Although the ID noncatalytic region has low composition and sequence complexity, it is possible to map microdomains, which are short linear motifs that are sites of interaction with protein and other ligands. Throughout bacteria, the composition of the multienzyme RNA degradosome varies with species, but interactions with exoribonucleases (PNPase, RNase R), glycolytic enzymes (enolase, aconitase) and RNA helicases (DEAD‐box proteins, Rho) are common. Plasticity in RNA degradosome composition is due to rapid evolution of RNase E microdomains. Characterization of the RNase E‐PNPase interaction in α‐proteobacteria, γ‐proteobacteria and cyanobacteria suggests that it arose independently several times during evolution, thus conferring an advantage in control and coordination of RNA processing and degradation.
Srr2, a multifaceted adhesin expressed by ST‐17 hypervirulent Group B Streptococcus involved in binding to both fibrinogen and plasminogen
Authors: Six Anne , Bellais Samuel , Bouaboud Abdelouhab , Fouet Agnès , Gabriel Christelle , Tazi Asmaa , Dramsi Shaynoor , Trieu‐Cuot Patrick , Poyart Claire
Published: June 2015

The Group B Streptococcus (GBS) ‘hypervirulent’ ST‐17 clone is strongly associated with invasive neonatal meningitis. Comparative genome analyses revealed that the serine‐rich repeat (Srr) glycoprotein Srr2 is a cell wall‐anchored protein specific for ST‐17 strains, the non‐ST‐17 isolates expressing Srr1. Here, we unravel the binding capacity of GBS Srr proteins to relevant components of the host fibrinolysis pathway. We demonstrate that: (i) Srr2 binds plasminogen and plasmin whereas Srr1 does not; (ii) the ability of ST‐17 strains to bind fibrinogen reflects a high level surface display of Srr2 combined with a higher affinity of Srr2 than Srr1 to bind this ligand; and (iii) Srr2 binding to host plasma proteins results in the formation of bacterial aggregates that are efficiently endocytosed by phagocytes. Importantly, we show that Srr2 increased bacterial survival to phagocytic killing and bacterial persistence in a murine model of meningitis. We conclude that Srr2 is a multifaceted adhesin used by the ST‐17 clone to hijack ligands of the host coagulation system, thereby contributing to bacterial dissemination and invasiveness, and ultimately to meningitis.
Bacillus subtilis SalA is a phosphorylation‐dependent transcription regulator that represses scoC and activates the production of the exoprotease AprE
Authors: Derouiche Abderahmane , Shi Lei , Bidnenko Vladimir , Ventroux Magali , Pigonneau Nathalie , Franz‐Wachtel Mirita , Kalantari Aida , Nessler Sylvie , Noirot‐Gros Marie‐Françoise , Mijakovic Ivan
Published: June 2015

Bacillus subtilis Mrp family protein SalA has been shown to indirectly promote the production of the exoprotease AprE by inhibiting the expression of scoC, which codes for a repressor of aprE. The exact mechanism by which SalA influences scoC expression has not been clarified previously. We demonstrate that SalA possesses a DNA‐binding domain (residues 1–60), which binds to the promoter region of scoC. The binding of SalA to its target DNA depends on the presence of ATP and is stimulated by phosphorylation of SalA at tyrosine 327. The B. subtilis protein‐tyrosine kinase PtkA interacts specifically with the C‐terminal domain of SalA in vivo and in vitro and is responsible for activating its DNA binding via phosphorylation of tyrosine 327. In vivo, a mutant mimicking phosphorylation of SalA (SalA Y327E) exhibited a strong repression of scoC and consequently overproduction of AprE. By contrast, the non‐phosphorylatable SalA Y327F and the ΔptkA exhibited the opposite effect, stronger expression of scoC and lower production of the exoprotease. Interestingly, both SalA and PtkA contain the same ATP‐binding Walker domain and have thus presumably arisen from the common ancestral protein. Their regulatory interplay seems to be conserved in other bacteria.
Regulation of Plasmodium falciparum Origin Recognition Complex subunit 1 (PfORC1) function through phosphorylation mediated by CDK‐like kinase PK5
Authors: Deshmukh Abhijit S. , Agarwal Meetu , Mehra Parul , Gupta Ashish , Gupta Nidhi , Doerig Christian D. , Dhar Suman Kumar
Published: June 2015

Plasmodium falciparum Origin Recognition Complex subunit 1 (PfORC1) has been implicated in DNA replication and var gene regulation. While the C‐terminus is involved in DNA replication, the specific role of N‐terminus has been suggested in var gene regulation in a Sir2‐dependent manner. PfORC1 is localized at the nuclear periphery, where the clustering of chromosomal ends at the early stage of parasite development may be crucial for the regulation of subtelomeric var gene expression. Upon disassembly of telomeric clusters at later stages of parasite development, ORC1 is distributed in the nucleus and parasite cytoplasm where it may be required for its other cellular functions including DNA replication. The level of ORC1 decreases dramatically at the late schizont stage. The mechanisms that mediate regulation of PfORC1 function are largely unknown. Here we show, by the use of recombinant proteins and of transgenic parasites expressing wild type or mutant forms of ORC1, that phosphorylation of the PfORC1‐N terminal domain by the cyclin‐dependent kinase (CDK) PfPK5 abolishes DNA‐binding activity and leads to changes in subcellular localization and proteasome‐mediated degradation of the protein in schizonts. These results reveal that PfORC1 phosphorylation by a CDK is central to the regulation of important biological functions like DNA replication and var gene silencing.
The durably resistant rice cultivar Digu activates defence gene expression before the full maturation of Magnaporthe oryzae appressorium
Authors: Li Weitao , Liu Ya , Wang Jing , He Min , Zhou Xiaogang , Yang Chao , Yuan Can , Wang Jichun , Chern Mawsheng , Yin Junjie , Chen Weilan , Ma Bingtian , Wang Yuping , Qin Peng , Li Shigui , Ronald Pamela , Chen Xuewei
Published: June 2015

Rice blast caused by the fungal pathogen Magnaporthe oryzae is one of the most destructive diseases worldwide. Although the rice–M. oryzae interaction has been studied extensively, the early molecular events that occur in rice before full maturation of the appressorium during M. oryzae invasion are unknown. Here, we report a comparative transcriptomics analysis of the durably resistant rice variety Digu and the susceptible rice variety Lijiangxintuanheigu (LTH) in response to infection by M. oryzae (5, 10 and 20 h post‐inoculation, prior to full development of the appressorium). We found that the transcriptional responses differed significantly between these two rice varieties. Gene ontology and pathway analyses revealed that many biological processes, including extracellular recognition and biosynthesis of antioxidants, terpenes and hormones, were specifically activated in Digu shortly after infection. Forty‐eight genes encoding receptor kinases (RKs) were significantly differentially regulated by M. oryzae infection in Digu. One of these genes, LOC_Os08g10300, encoding a leucine‐rich repeat RK from the LRR VIII‐2 subfamily, conferred enhanced resistance to M. oryzae when overexpressed in rice. Our study reveals that a multitude of molecular events occur in the durably resistant rice Digu before the full maturation of the appressorium after M. oryzae infection and that membrane‐associated RKs play important roles in the early response.
Borrelia burgdorferi sensu lato and co‐infections with Anaplasma phagocytophilum and Rickettsia spp. in Ixodes ricinus in Hamburg, Germany
Authors: MAY K. , JORDAN D. , FINGERLE V. , STRUBE C.
Published: June 2015

To obtain initial data on Borrelia burgdorferi sensu lato (Spirochaetales: Spirochaetaceae) in Ixodes ricinus (Ixodida: Ixodidae) ticks in Hamburg, Germany, 1400 questing ticks were collected by flagging at 10 different public recreation areas in 2011 and analysed using probe‐based quantitative real‐time polymerase chain reaction. The overall rate of infection with B. burgdorferi s.l. was 34.1%; 30.0% of adults were infected (36.7% of females and 26.0% of males), as were 34.5% of nymphs. Significant differences in tick infection rates were observed between the spring and summer/autumn months, as well as among sampling locations. Borrelia genospecies identification by reverse line blotting was successful in 43.6% of positive tick samples. The most frequent genospecies was Borrelia garinii/Borrelia bavariensis, followed by Borrelia afzelii, Borrelia valaisiana, B. burgdorferi sensu stricto, Borrelia spielmanii, Borrelia bissettii and Borrelia lusitaniae. Based on previously published data, co‐infection of Borrelia and Rickettsiales spp. was determined in 25.8% of ticks. Overall, 22.9% of ticks were co‐infected with Rickettsia spp. (Rickettsiales: Rickettsiaceae), 1.7% with Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae), and 1.2% with both pathogens. Study results show a high prevalence of Borrelia‐positive ticks in recreation areas in the northern German city of Hamburg and the potential health risk to humans in these areas should not be underestimated.
Neuronal DNA damage response‐associated dysregulation of signalling pathways and cholesterol metabolism at the earliest stages of Alzheimer‐type pathology
Authors: Simpson Julie E. , Ince Paul G. , Minett Thais , Matthews Fiona E. , Heath Paul R. , Shaw Pamela J. , Goodall Emily , Garwood Claire J. , Ratcliffe Laura E. , Brayne Carol , Rattray Magnus , Wharton Stephen B. ,   the MRC Cognitive Function and Ageing Neuropathology Study Group
Published: June 2015

Aims

Oxidative damage and an associated DNA damage response (DDR) are evident in mild cognitive impairment and early Alzheimer's disease, suggesting that neuronal dysfunction resulting from oxidative DNA damage may account for some of the cognitive impairment not fully explained by Alzheimer‐type pathology.

Methods

Frontal cortex (Braak stage 0–II) was obtained from the Medical Research Council's Cognitive Function and Ageing Study cohort. Neurones were isolated from eight cases (four high and four low DDR) by laser capture microdissection and changes in the transcriptome identified by microarray analysis.

Results

Two thousand three hundred seventy‐eight genes were significantly differentially expressed (1690 up‐regulated, 688 down‐regulated, P < 0.001) in cases with a high neuronal DDR. Functional grouping identified dysregulation of cholesterol biosynthesis, insulin and Wnt signalling, and up‐regulation of glycogen synthase kinase 3β. Candidate genes were validated by quantitative real‐time polymerase chain reaction. Cerebrospinal fluid levels of 24(S)‐hydroxycholesterol associated with neuronal DDR across all Braak stages (rs = 0.30, P = 0.03).

Conclusions

A persistent neuronal DDR may result in increased cholesterol biosynthesis, impaired insulin and Wnt signalling, and increased GSK3β, thereby contributing to neuronal dysfunction independent of Alzheimer‐type pathology in the ageing brain.
Polyglutamine aggregation inHuntington's disease and spinocerebellar ataxia type 3: similar mechanisms in aggregate formation
Authors: Seidel K. , Siswanto S. , Fredrich M. , Bouzrou M. , Brunt E. R. , van Leeuwen F. W. , Kampinga H. H. , Korf H. ‐W. , Rüb U. , den Dunnen W. F. A.
Published: June 2015

Aims

Polyglutamine (polyQ) diseases are characterized by the expansion of a polymorphic glutamine sequence in disease‐specific proteins and exhibit aggregation of these proteins. This is combated by the cellular protein quality control (PQC) system, consisting of chaperone‐mediated refolding as well as proteasomal and lysosomal degradation pathways. Our recent study in thepolyQdisease spinocerebellar ataxia type 3 (SCA3) suggested a distinct pattern of protein aggregation andPQCdysregulation.

Methods

To corroborate these findings we have investigated immunohistochemically stained 5 μm sections from different brain areas ofHuntington's disease (HD) andSCA3patients.

Results

Irrespective of disease and brain region, we observed peri‐ and intranuclearpolyQprotein aggregates. A subset of neurones with intranuclear inclusions bodies exhibited signs of proteasomal dysfunction, up‐regulation ofHSPA1Aand re‐distribution ofDNAJB1. The extent of the observed effects varied depending on brain area and disease protein.

Conclusions

Our results suggest a common sequence, in which formation of cytoplasmic and nuclear inclusions precede proteasomal impairment and induction of the cellular stress response. Clearly, impairment of thePQCis not the primary cause for inclusion formation, but rather a consequence that might contribute to neuronal dysfunction and death. Notably, the inclusion pathology is not directly correlated to the severity of the degeneration in different areas, implying that different populations of neurones respond topolyQaggregation with varying efficacy and that protein aggregation outside the neuronal perikaryon (e.g. axonal aggregates) or other effects ofpolyQaggregation, which are more difficult to visualize, may contribute to neurodegeneration.
Long‐term outcomes for primary glomerulonephritis: New Zealand Glomerulonephritis Study
Authors: Chembo Caroline L , Marshall Mark R , Williams Laurie C , Walker Robert J , Lynn Kelvin L , Irvine John , Pilmore Helen L
Published: June 2015

Aims

Due to the paucity of studies focusing on primary glomerulonephritis, the second commonest cause of end‐stage‐kidney‐disease in most of the developed world, we sought to review outcomes of these renal pathologies.

Methods

We reviewed renal outcomes and mortality for primary glomerulonephritis patients enrolled in the New Zealand Glomerulonephritis Study between 1972 and 1983.

Results

There were 765 patients with median follow‐up of 30 years (range 0.1–42 years). They were predominantly New Zealand European, male and hypertensive. Poor renal outcomes and increased mortality were associated with hypertension, heavy proteinuria, impaired renal function and older age at diagnosis. Ethnicity was not significantly associated with progression to end‐stage‐kidney‐disease although NZ Maori patients were at significantly increased risk of death. Patients with rapidly progressive glomerulonephritis had the highest risk of reaching end‐stage‐kidney‐disease while the cumulative incidence of end‐stage‐kidney‐disease was 20% and 30% for those with immunoglobulin‐A nephropathy and membranous nephropathy respectively. Mortality risk was high for patients with rapidly progressive glomerulonephritis and anti‐glomerular basement membrane disease. The era of diagnosis did not have much effect on outcomes except for patients with focal segmental glomerulosclerosis or immunoglobulin A nephropathy but this could be type II error.

Conclusion

We report one of the longest follow‐up studies on biopsy‐proven glomerulonephritides. Age, hypertension, and severity of chronic kidney disease at diagnosis were strong predictors of the development of end‐stage‐kidney‐disease and death. The specific renal pathology had a profound impact upon prognosis and therefore should continue to drive efforts to find targeted therapeutic options for these glomerulonephritides.
Localization of nuclear receptor subfamily 4, group A, member 3 (NR4A3) in Lewy body disease and multiple system atrophy
Authors: Kon Tomoya , Miki Yasuo , Tanji Kunikazu , Mori Fumiaki , Tomiyama Masahiko , Toyoshima Yasuko , Kakita Akiyoshi , Takahashi Hitoshi , Utsumi Jun , Sasaki Hidenao , Wakabayashi Koichi
Published: June 2015

Nuclear receptor subfamily 4, group A, member 3 (NR4A3), also known as neuron‐derived orphan receptor‐1, is a nuclear receptor which plays key roles in cell cycle, neuronal differentiation, apoptosis and metabolism. These processes may be involved in the pathogenesis of certain neurodegenerative diseases. Previous studies have shown that there are high levels of NR4A3 mRNA in the CNS. Moreover, NR4A2, a transcription factor with homology to NR4A3, has been reported to contribute to the pathogenesis of Parkinson's disease. However, it is uncertain whether NR4A3 is also involved in diseases such as dementia with Lewy bodies, multiple system atrophy, and other neurodegenerative disorders such as tauopathies, TDP‐43 proteinopathies and polyglutamine diseases. In the present study we used immunohistochemistry to examine the brain and spinal cord from patients with various neurodegenerative diseases and normal control subjects using two polyclonal anti‐NR4A3 antibodies. In controls, the cytoplasm of neurons and glial cells was faintly immunostained with anti‐NR4A3 antibodies. In tissues from patients with neurodegenerative diseases, immunoreactivity for NR4A3 was observed in cortical and brainstem‐type Lewy bodies in Parkinson's disease and in dementia with Lewy bodies, as well as in neuronal and glial cytoplasmic inclusions in multiple system atrophy. A double‐labeled immunofluorescence study showed co‐localization of NR4A3 and phosphorylated α‐synuclein in these inclusions. Neuronal and glial inclusions in other neurodegenerative disorders were NR4A3 negative. These findings suggest that accumulation of NR4A3 is specific to α‐synucleinopathy.
Alchemilla schmakovii sp. nov. from eastern Europe
Authors: Chkalov Andrey V.
Published: June 2015

A morphological study of specimens collected by the author and a critical revision of the key herbarium collections revealed a new rather peculiar taxon of Alchemilla occurring in almost every region of the Middle Volga basin, Russia. This novelity is here described as A. schmakovii and images of the principal morphological features of this species are provided. The new species is compared with related species in A. sect. Alchemilla (e.g. A. micans) and sect. Plicatae (e.g. A. breviloba) based on morphological characteristics.
Reduction of hydrogen sulfide synthesis enzymes in the esophagus of patients with achalasia: effect of hydrogen sulfide in achalasia
Authors: Zhang L. , Zhao W. , Zheng Z. , Wang T. , Zhao C. , Zhou G. , Jin H. , Wang B.
Published: June 2015

Background

The aim of the present study was to investigate whether the synthesis of endogenous hydrogen sulfide (H2S) was altered in achalasia patients and to determine the effects of H2S on esophageal motility.

Methods

(1) Tissue samples in lower esophageal sphincter (LES) were obtained from 22 achalasia patients during peroral endoscopic myotomy. LES muscle from eight esophageal carcinoma patients was obtained as control. The expression of cystathionine‐β‐synthase (CBS) and cystathionine‐γ‐lyase (CSE) was detected by immunohistochemical staining. (2) Rabbit esophageal smooth muscle strips were used to measure isometric contractions. The effects of sodium hydrosulfide (NaHS) and L‐cysteine on contractile activity and bethanechol‐stimulated contractile activity were evaluated. The contraction of esophageal muscle strips was also measured after the inhibition of CBS and CSE by aminooxyacetic acid (AOA) and propargylglycine (PAG).

Key Results

Both CBS and CSE could be detected in biopsies from achalasia patients and controls. Compared with controls, the expression of CBS and CSE in the LES of achalasia patients was significantly reduced (p < 0.001). Both NaHS and L‐cysteine concentration‐dependently inhibited esophageal contractile activity (both p < 0.05). After inhibition of CBS and CSE by PAG and AOA, esophageal contractile activity increased significantly, and this effect could be restored by NaHS but not L‐cysteine (p < 0.05).

Conclusions & Inferences

H2S synthesis enzymes are significantly reduced in patients with achalasia compared with the controls. H2S inhibits esophageal contractile activity concentration‐dependently, and the inhibition of H2S synthesis enzymes increases esophageal contractile activity. H2S might be involved in the development of achalasia.
Adapting through glacial cycles: insights from a long‐lived tree (Taxus baccata)
Authors: Mayol Maria , Riba Miquel , González‐Martínez Santiago C. , Bagnoli Francesca , de Beaulieu Jacques‐Louis , Berganzo Elisa , Burgarella Concetta , Dubreuil Marta , Krajmerová Diana , Paule Ladislav , Romšáková Ivana , Vettori Cristina , Vincenot Lucie , Vendramin Giovanni G.
Published: June 2015

Despite the large body of research devoted to understanding the role of Quaternary glacial cycles in the genetic divergence of European trees, the differential contribution of geographic isolation and/or environmental adaptation in creating population genetic divergence remains unexplored. In this study, we used a long‐lived tree (Taxus baccata) as a model species to investigate the impact of Quaternary climatic changes on genetic diversity via neutral (isolation‐by‐distance) and selective (isolation‐by‐adaptation) processes.

We applied approximate Bayesian computation to genetic data to infer its demographic history, and combined this information with past and present climatic data to assess the role of environment and geography in the observed patterns of genetic structure.

We found evidence that yew colonized Europe from the East, and that European samples diverged into two groups (Western, Eastern) at the beginning of the Quaternary glaciations, c. 2.2 Myr before present. Apart from the expected effects of geographical isolation during glacials, we discovered a significant role of environmental adaptation during interglacials at the origin of genetic divergence between both groups.

This process may be common in other organisms, providing new research lines to explore the effect of Quaternary climatic factors on present‐day patterns of genetic diversity.
Genetic interactions between diverged alleles of Early heading date 1 (Ehd1) and Heading date 3a (Hd3a)/ RICE FLOWERING LOCUS T1 (RFT1) control differential heading and contribute to regional adaptation in rice (Oryza sativa)
Authors: Zhao Jing , Chen Hongyi , Ren Ding , Tang Huiwu , Qiu Rong , Feng Jinglei , Long Yunming , Niu Baixiao , Chen Danping , Zhong Tianyu , Liu Yao‐Guang , Guo Jingxin
Published: June 2015

Initiation of flowering, also called heading, in rice (Oryza sativa) is determined by the florigens encoded by Heading date 3a (Hd3a) and RICE FLOWERING LOCUS T1 (RFT1). Early heading date 1 (Ehd1) regulates Hd3a and RFT1. However, different rice varieties have diverged alleles of Ehd1 and Hd3a/RFT1 and their genetic interactions remain largely unclear.

Here we generated three segregating populations for different combinations of diverged Ehd1 and Hd3a/RFT1 alleles, and analyzed their genetic interactions between these alleles. We demonstrated that, in an ehd1 mutant background, Hd3a was silenced, but RFT1 was expressed (although at lower levels than in plants with a functional Ehd1) under short‐day (SD) and long‐day (LD) conditions.

We identified a nonfunctional RFT1 allele (rft1); the lines carrying homozygous ehd1 and Hd3a/rft1 failed to induce the floral transition under SD and LD conditions. Like Hd3a, RFT1 also interacted with 14‐3‐3 proteins, the florigen receptors, but a nonfunctional RFT1 with a crucial E105K mutation failed to interact with 14‐3‐3 proteins. Furthermore, analyses of sequence variation and geographic distribution suggested that functional RFT1 alleles were selected during rice adaptation to high‐latitude regions.

Our results demonstrate the important roles of RFT1 in rice flowering and regional adaptation.
The Casuarina NIN gene is transcriptionally activated throughout Frankia root infection as well as in response to bacterial diffusible signals
Authors: Clavijo Fernando , Diedhiou Issa , Vaissayre Virginie , Brottier Laurent , Acolatse Jennifer , Moukouanga Daniel , Crabos Amandine , Auguy Florence , Franche Claudine , Gherbi Hassen , Champion Antony , Hocher Valerie , Barker David , Bogusz Didier , Tisa Louis S. , Svistoonoff Sergio
Published: June 2015

Root nodule symbioses (RNS) allow plants to acquire atmospheric nitrogen by establishing an intimate relationship with either rhizobia, the symbionts of legumes or Frankia in the case of actinorhizal plants. In legumes, NIN (Nodule INception) genes encode key transcription factors involved in nodulation.

Here we report the characterization of CgNIN, a NIN gene from the actinorhizal tree Casuarina glauca using both phylogenetic analysis and transgenic plants expressing either ProCgNIN::reporter gene fusions or CgNIN RNAi constructs.

We have found that CgNIN belongs to the same phylogenetic group as other symbiotic NIN genes and CgNIN is able to complement a legume nin mutant for the early steps of nodule development. CgNIN expression is correlated with infection by Frankia, including preinfection stages in developing root hairs, and is induced by culture supernatants. Knockdown mutants were impaired for nodulation and early root hair deformation responses were severely affected. However, no mycorrhizal phenotype was observed and no induction of CgNIN expression was detected in mycorrhizas.

Our results indicate that elements specifically required for nodulation include NIN and possibly related gene networks derived from the nitrate signalling pathways.
Neuroendocrine mechanisms underlying behavioral stability: implications for the evolutionary origin of personality
Authors: Duckworth Renée A.
Published: June 2015

Personality traits are behaviors that show limited flexibility over time and across contexts, and thus understanding their origin requires an understanding of what limits behavioral flexibility. Here, I suggest that insight into the evolutionary origin of personality traits requires determining the relative importance of selection and constraint in producing limits to behavioral flexibility. Natural selection as the primary cause of limits to behavioral flexibility assumes that the default state of behavior is one of high flexibility and predicts that personality variation arises through evolution of buffering mechanisms to stabilize behavioral expression, whereas the constraint hypothesis assumes that the default state is one of limited flexibility and predicts that the neuroendocrine components that underlie personality variation are those most constrained in flexibility. Using recent work on the neurobiology of sensitive periods and maternal programming of offspring behavior, I show that some of the most stable aspects of the neuroendocrine system are structural components and maternally induced epigenetic effects. Evidence of numerous constraints to changes in structural features of the neuroendocrine system and far fewer constraints to flexibility of epigenetic systems suggests that structural constraints play a primary role in the origin of behavioral stability and that epigenetic programming may be more important in generating adaptive variation among individuals.
NF‐κB signaling in B‐1 cell development
Authors: Pedersen Gabriel K. , Ádori Monika , Hedestam Gunilla B. Karlsson
Published: June 2015

NF‐κB transcription factors play essential roles in hematopoiesis. In this review, we summarize the requirements of different components of the NF‐κB pathway for B‐1 cell development and maintenance. The B‐1 cell developmental steps are also reviewed, with particular emphasis on stages where NF‐κB signaling may be critical.
Maternal body mass index and risk of birth and maternal health outcomes in low‐ and middle‐income countries: a systematic review and meta‐analysis
Authors: Rahman M. M. , Abe S. K. , Kanda M. , Narita S. , Rahman M. S. , Bilano V. , Ota E. , Gilmour S. , Shibuya K.
Published: June 2015

We conducted a systematic review and meta‐analysis of population‐based cohort studies of maternal body mass index (BMI) and risk of adverse birth and health outcomes in low‐ and middle‐income countries. PubMed, Embase, CINAHL and the British Nursing Index were searched from inception to February 2014. Forty‐two studies were included. Our study found that maternal underweight was significantly associated with higher risk of preterm birth (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.01–1.27), low birthweight (OR, 1.66; 95% CI, 1.50–1.84) and small for gestational age (OR, 1.85; 95% CI, 1.69–2.02). Compared with mothers with normal BMI, overweight or obese mothers were at increased odds of gestational diabetes, pregnancy‐induced hypertension, pre‐eclampsia, caesarean delivery and post‐partum haemorrhage. The population‐attributable risk (PAR) indicated that if women were entirely unexposed to overweight or obesity during the pre‐pregnancy or early pregnancy period, 14% to 35% fewer women would develop gestational diabetes, pre‐eclampsia or pregnancy‐induced hypertension in Brazil, China, India, Iran or Thailand. The highest PAR of low birthweight attributable to maternal underweight was found in Iran (20%), followed by India (18%), Thailand (10%) and China (8%). Treatment and prevention of maternal underweight, overweight or obesity may help reduce the burden on maternal and child health in developing countries.
Pulmonary Vein Isolation Using the First‐Generation Cryoballoon Technique in Chinese Patients
Authors: ZHOU GONG‐BU , GUO XIAO‐GANG , LIU XU , YANG JIAN‐DU , SUN QI , MA JIAN , ZHANG SHU
Published: June 2015

Background

Cryoballoon ablation is an alternative for the treatment of atrial fibrillation (AF). We assess the relationship among pulmonary vein (PV) electrophysiology, balloon temperature, and persistent PV isolation (PVI), and report procedural properties, safety, and efficacy of this technique in a Chinese center for the first time.

Methods

A total of 70 patients with paroxysmal (n = 57) and persistent (n = 13) AF were consecutively enrolled. PVI was performed with cryoballoon catheter. Real‐time recording of dissociation of PV potentials was attempted using a circumferential mapping catheter.

Results

Successful PVI was achieved in 274 of 282 (97.2%) PVs. Procedural duration was 115.2 ± 24.8 minutes and fluoroscopy time was 29.6 ± 8.9 minutes. Real‐time PV potential recording was achieved in 232 (84.3%) PVs. Regarding time to isolation, a cut‐off value of less than 60 seconds was predictive of persistent PVI with a sensitivity of 0.76 and specificity of 0.82 (area under curve = 0.835; P < 0.0001). The nadir balloon temperature was significantly lower in PVs without early reconduction (–46.3 ± 0.5°C vs –40.2 ± 1.3°C, P < 0.0001). However, there was an insignificant trend that the balloon temperature at isolation was higher in PVs without reconduction (–33.9 ± 0.7°C vs –36.4 ± 2.0°C, P = 0.14). The overall complication rate was 5.7%. After a median follow‐up of 6.5 (range 3.2–14.9) months, 76% of patients were free of AF recurrence with a blanking period of 3 months.

Conclusions

Real‐time PV potentials can be recorded in most PVs. The time to isolation is predictive of the persistency of PVI. The nadir balloon temperature, not the balloon temperature at isolation, is significantly lower in PVs without reconduction.
QRS Duration Changes in Patients with Single Ventricle Physiology: Birth to 10 Years
Authors: KHAN SAIRAH , NADORLIK HOLLY , KERTESZ NAOMI , NICHOLSON LISA , RO PAMELA S. , CUA CLIFFORD L.
Published: June 2015

Background

QRS prolongation may be a predictor of mortality in certain forms of congenital heart disease. Minimal data exist describing changes in QRS duration in patients with single ventricles (SVs). The goal was to describe changes in QRS duration in patients with SV and to determine if differences existed between single right ventricle (sRV) versus single left ventricle (sLV) patients.

Methods

Chart review was performed on patients with SV physiology. Patients were divided into sRV and sLV groups. QRS durations were measured monthly for the first 6 months, at 1 year, and then yearly until 10 years. t‐tests were used for analysis.

Results

One hundred sixty patients were evaluated (95 sRV, 65 sLV). The greatest change in QRS duration for the entire cohort occurred in the first 6 months of life versus 6 months to 10 years of age (1.81 ms/month vs 0.20 ms/month). sRV QRS durations were significantly longer than sLV QRS durations at 1 year (78.9 ± 12.6 ms vs 73.2 ± 11.9 ms), 2 year (81.7 ± 14.7 ms vs 73.4 ± 12.5 ms), 4 year (84.2 ± 12.1 ms vs 77.9 ± 16.4 ms), 6 year (90.8 ± 12.7 ms vs 83.4 ± 13.4 ms), 7 year (90.8 ± 16.5 ms vs 81.2 ± 16.6 ms), and 8 year (96.7 ± 13.6 ms vs 84.8 ± 13.9 ms) time points.

Conclusion

The greatest change in QRS duration in SV patients occurred in the first 6 months of life when these patients’ ventricles were volume loaded. Differences in QRS duration between sRV and sLV patients occurred early in life. Further studies are needed to determine if minimizing volume load early in life decreases the rate of change in QRS duration.
Sevoflurane exposure during the neonatal period induces long‐term memory impairment but not autism‐like behaviors
Authors: Chung Woosuk , Park Saegeun , Hong Jiso , Park Sangil , Lee Soomin , Heo Junyoung , Kim Daesoo , Ko Youngkwon
Published: June 2015

Objective

To examine whether neonatal exposure to sevoflurane induces autism‐like behaviors in mice.

Background

There are continuing reports regarding the potential negative effects of anesthesia on the developing brain. Recently, several studies suggest that neurotoxicity caused by anesthesia may lead to neurodevelopmental impairments. However, unlike reports focusing on learning and memory, there are only a few animal studies focusing on neurodevelopmental disorders after general anesthesia. Therefore, we have focused on autism, a representative neurodevelopmental disorder.

Methods

Neonatal mice (P6–7) were exposed to a titrated dose of sevoflurane for 6 h. Apoptosis was evaluated by assessing the expression level of cleaved (activated) caspase‐3. Autism‐like behaviors, general activity, anxiety level, and long‐term memory were evaluated with multiple behavioral assays.

Results

Western blotting confirmed that neonatal exposure to sevoflurane increased the expression level of activated caspase‐3, indicative of apoptosis. Mice exposed to sevoflurane also showed impaired long‐term memory in fear tests. However, sevoflurane‐exposed mice did not exhibit autism‐like features in all of the following assays: social interaction (three‐chamber test, caged social interaction), social communication (ultrasonic vocalization test), or repetitive behavior (self‐grooming test, digging). There were also no differences in general activity (open field test, home cage activity) and anxiety (open field test, light‐dark box) after sevoflurane exposure.

Conclusions

Our results confirm previous studies that neonatal sevoflurane exposure causes neurodegeneration and long‐term memory impairment in mice. However, sevoflurane did not induce autism‐like features. Our study suggests that mice are more vulnerable to long‐term memory deficits than autism‐like behaviors after exposure to sevoflurane.
Complex Regional Pain Syndrome in Children: a Multidisciplinary Approach and Invasive Techniques for the Management of Nonresponders
Authors: Rodriguez‐ Lopez Manuel J. , Fernandez‐Baena Mariano , Barroso Alex , Yáñez‐Santos Jose A.
Published: June 2015

Complex regional pain syndrome (CRPS) is multifactorial condition with complex pathogenesis characterized by spontaneous or stimulus‐induced pain that is disproportionate to the inciting event. It is also commonly accompanied by a myriad of autonomic and motor disturbances in highly variable combinations. This condition has been underreported in children until recently. Consequently, the management of CRPS in the pediatric population presents an even greater challenge than in adults, partly because there is a lack of clinical data concerning the efficacy of the diverse treatment methods available, and partly because successful treatment of CRPS involves a multidisciplinary approach. In this retrospective case series, a multidisciplinary management plan is presented in 10 children for whom the standard noninvasive treatment was unsuccessful. Within this management plan, novel drugs were included such as the capsaicin 8% patch, in addition to invasive techniques in patients who did not respond to noninvasive therapies.
Pedigree‐based analysis of derivation of genome segments of an elite rice reveals key regions during its breeding
Authors: Zhou Degui , Chen Wei , Lin Zechuan , Chen Haodong , Wang Chongrong , Li Hong , Yu Renbo , Zhang Fengyun , Zhen Gang , Yi Junliang , Li Kanghuo , Liu Yaoguang , Terzaghi William , Tang Xiaoyan , He Hang , Zhou Shaochuan , Deng Xing Wang
Published: June 2015

Analyses of genome variations with high‐throughput assays have improved our understanding of genetic basis of crop domestication and identified the selected genome regions, but little is known about that of modern breeding, which has limited the usefulness of massive elite cultivars in further breeding. Here we deploy pedigree‐based analysis of an elite rice, Huanghuazhan, to exploit key genome regions during its breeding. The cultivars in the pedigree were resequenced with 7.6× depth on average, and 2.1 million high‐quality single nucleotide polymorphisms (SNPs) were obtained. Tracing the derivation of genome blocks with pedigree and information on SNPs revealed the chromosomal recombination during breeding, which showed that 26.22% of Huanghuazhan genome are strictly conserved key regions. These major effect regions were further supported by a QTL mapping of 260 recombinant inbred lines derived from the cross of Huanghuazhan and a very dissimilar cultivar, Shuanggui 36, and by the genome profile of eight cultivars and 36 elite lines derived from Huanghuazhan. Hitting these regions with the cloned genes revealed they include numbers of key genes, which were then applied to demonstrate how Huanghuazhan were bred after 30 years of effort and to dissect the deficiency of artificial selection. We concluded the regions are helpful to the further breeding based on this pedigree and performing breeding by design. Our study provides genetic dissection of modern rice breeding and sheds new light on how to perform genomewide breeding by design.
Melanopsin photoreception in the eye regulates light‐induced skin colour changes through the production of α‐MSH in the pituitary gland
Authors: Bertolesi Gabriel E. , Hehr Carrie L. , McFarlane Sarah
Published: June 2015

How skin colour adjusts to circadian light/dark cycles is poorly understood. Melanopsin (Opn4) is expressed in melanophores, where in vitro studies suggest it regulates skin pigmentation through a ‘primary colour response’ in which light photosensitivity is translated directly into pigment movement. However, the entrainment of the circadian rhythm is regulated by a population of melanopsin‐expressing retinal ganglion cells (mRGCs) in the eye. Therefore, in vivo, melanopsin may trigger a ‘secondary colour response’ initiated in the eye and controlled by the neuro‐endocrine system. We analysed the expression of opn4m and opn4x and melanin aggregation induced by light (background adaptation) in Xenopus laevis embryos. While opn4m and opn4x are expressed at early developmental times, light‐induced pigment aggregation requires the eye to become functional. Pharmacological inhibition of melanopsin suggests a model whereby mRGC activation lightens skin pigmentation via a secondary response involving negative regulation of alpha‐melanocyte‐stimulating hormone (α‐MSH) secretion by the pituitary.
Recurrent Kawasaki disease: USA and Japan
Authors: Maddox Ryan A , Holman Robert C , Uehara Ritei , Callinan Laura S , Guest Jodie L , Schonberger Lawrence B , Nakamura Yosikazu , Yashiro Mayumi , Belay Ermias D
Published: June 2015

Background

Descriptive epidemiologic studies of recurrent and non‐recurrent Kawasaki disease (KD) may identify other potentially important differences between these illnesses.

Methods

Data from the USA and Japan, the Centers for Disease Control and Prevention (CDC) national KD surveillance(1984–2008) and the 17th Japanese nationwide survey (2001–2002), respectively, were analyzed to examine recurrent KD patients <18 years of age meeting the CDC KD case or atypical KD case definition. These patients were compared with non‐recurrent KD patients.

Results

Of the 5557 US KD patients <18 years of age during 1984–2008, 97 (1.7%) were identified as having had recurrent KD. Among the US Asian/Pacific Islander KD patients, 3.5% had recurrent KD, which was similar to the percentage identified among KD patients (3.5%) in the Japanese survey. Compared with non‐recurrent KD patients, KD patients [with recurrent KD] were more likely to be older, fulfill the atypical KD case definition, and have coronary artery abnormalities (CAA) despite i.v. immunoglobulin (IVIG) treatment.

Conclusions

Differences in the age, race, and frequency of CAA exist between recurrent and non‐recurrent KD patients. The increased association of CAA with recurrent KD suggests that more aggressive treatment strategies in conjunction with IVIG may be indicated for the second episode of KD.