bluuebunny/crossref_metadata_2025 huggingface dataset:
Translocations of Chromosome End-Segments and Facultative Heterochromatin Promote Meiotic Ring Formation in Evening Primroses
Authors: Golczyk Hieronim , Massouh Amid , Greiner Stephan
Published: March 2014

Due to reciprocal chromosomal translocations, many species of Oenothera (evening primrose) form permanent multichromosomal meiotic rings. However, regular bivalent pairing is also observed. Chiasmata are restricted to chromosomal ends, which makes homologous recombination virtually undetectable. Genetic diversity is achieved by changing linkage relations of chromosomes in rings and bivalents via hybridization and reciprocal translocations. Although the structural prerequisite for this system is enigmatic, whole-arm translocations are widely assumed to be the mechanistic driving force. We demonstrate that this prerequisite is genome compartmentation into two epigenetically defined chromatin fractions. The first one facultatively condenses in cycling cells into chromocenters negative both for histone H3 dimethylated at lysine 4 and for C-banding, and forms huge condensed middle chromosome regions on prophase chromosomes. Remarkably, it decondenses in differentiating cells. The second fraction is euchromatin confined to distal chromosome segments, positive for histone H3 lysine 4 dimethylation and for histone H3 lysine 27 trimethylation. The end-segments are deprived of canonical telomeres but capped with constitutive heterochromatin. This genomic organization promotes translocation breakpoints between the two chromatin fractions, thus facilitating exchanges of end-segments. We challenge the whole-arm translocation hypothesis by demonstrating why reciprocal translocations of chromosomal end-segments should strongly promote meiotic rings and evolution toward permanent translocation heterozygosity. Reshuffled end-segments, each possessing a major crossover hot spot, can furthermore explain meiotic compatibility between genomes with different translocation histories.
Global Dissection of Alternative Splicing in Paleopolyploid Soybean
Authors: Shen Yanting , Zhou Zhengkui , Wang Zheng , Li Weiyu , Fang Chao , Wu Mian , Ma Yanming , Liu Tengfei , Kong Ling-An , Peng De-Liang , Tian Zhixi
Published: March 2014

Alternative splicing (AS) is common in higher eukaryotes and plays an important role in gene posttranscriptional regulation. It has been suggested that AS varies dramatically among species, tissues, and duplicated gene families of different sizes. However, the genomic forces that govern AS variation remain poorly understood. Here, through genome-wide identification of AS events in the soybean (Glycine max) genome using high-throughput RNA sequencing of 28 samples from different developmental stages, we found that more than 63% of multiexonic genes underwent AS. More AS events occurred in the younger developmental stages than in the older developmental stages for the same type of tissue, and the four main AS types, exon skipping, intron retention, alternative donor sites, and alternative acceptor sites, exhibited different characteristics. Global computational analysis demonstrated that the variations of AS frequency and AS types were significantly correlated with the changes of gene features and gene transcriptional level. Further investigation suggested that the decrease of AS within the genome-wide duplicated genes were due to the diminution of intron length, exon number, and transcriptional level. Altogether, our study revealed that a large number of genes were alternatively spliced in the soybean genome and that variations in gene structure and transcriptional level may play important roles in regulating AS.
Evolutionary Origins of a Bioactive Peptide Buried within Preproalbumin
Authors: Elliott Alysha G. , Delay Christina , Liu Huanle , Phua Zaiyang , Rosengren K. Johan , Benfield Aurélie H. , Panero Jose L. , Colgrave Michelle L. , Jayasena Achala S. , Dunse Kerry M. , Anderson Marilyn A. , Schilling Edward E. , Ortiz-Barrientos Daniel , Craik David J. , Mylne Joshua S.
Published: March 2014

The de novo evolution of proteins is now considered a frequented route for biological innovation, but the genetic and biochemical processes that lead to each newly created protein are often poorly documented. The common sunflower (Helianthus annuus) contains the unusual gene PawS1 (Preproalbumin with SFTI-1) that encodes a precursor for seed storage albumin; however, in a region usually discarded during albumin maturation, its sequence is matured into SFTI-1, a protease-inhibiting cyclic peptide with a motif homologous to unrelated inhibitors from legumes, cereals, and frogs. To understand how PawS1 acquired this additional peptide with novel biochemical functionality, we cloned PawS1 genes and showed that this dual destiny is over 18 million years old. This new family of mostly backbone-cyclic peptides is structurally diverse, but the protease-inhibitory motif was restricted to peptides from sunflower and close relatives from its subtribe. We describe a widely distributed, potential evolutionary intermediate PawS-Like1 (PawL1), which is matured into storage albumin, but makes no stable peptide despite possessing residues essential for processing and cyclization from within PawS1. Using sequences we cloned, we retrodict the likely stepwise creation of PawS1's additional destiny within a simple albumin precursor. We propose that relaxed selection enabled SFTI-1 to evolve its inhibitor function by converging upon a successful sequence and structure.
Discovery of a Chlorophyll Binding Protein Complex Involved in the Early Steps of Photosystem II Assembly in Synechocystis
Authors: Knoppová Jana , Sobotka Roman , Tichý Martin , Yu Jianfeng , Konik Peter , Halada Petr , Nixon Peter J. , Komenda Josef
Published: March 2014

Efficient assembly and repair of the oxygen-evolving photosystem II (PSII) complex is vital for maintaining photosynthetic activity in plants, algae, and cyanobacteria. How chlorophyll is delivered to PSII during assembly and how vulnerable assembly complexes are protected from photodamage are unknown. Here, we identify a chlorophyll and β-carotene binding protein complex in the cyanobacterium Synechocystis PCC 6803 important for formation of the D1/D2 reaction center assembly complex. It is composed of putative short-chain dehydrogenase/reductase Ycf39, encoded by the slr0399 gene, and two members of the high-light-inducible protein (Hlip) family, HliC and HliD, which are small membrane proteins related to the light-harvesting chlorophyll binding complexes found in plants. Perturbed chlorophyll recycling in a Ycf39-null mutant and copurification of chlorophyll synthase and unassembled D1 with the Ycf39-Hlip complex indicate a role in the delivery of chlorophyll to newly synthesized D1. Sequence similarities suggest the presence of a related complex in chloroplasts.
A Cyanobacterial Chlorophyll Synthase-HliD Complex Associates with the Ycf39 Protein and the YidC/Alb3 Insertase
Authors: Chidgey Jack W. , Linhartová Markéta , Komenda Josef , Jackson Philip J. , Dickman Mark J. , Canniffe Daniel P. , Koník Peter , Pilný Jan , Hunter C. Neil , Sobotka Roman
Published: March 2014

Macromolecular membrane assemblies of chlorophyll-protein complexes efficiently harvest and trap light energy for photosynthesis. To investigate the delivery of chlorophylls to the newly synthesized photosystem apoproteins, a terminal enzyme of chlorophyll biosynthesis, chlorophyll synthase (ChlG), was tagged in the cyanobacterium Synechocystis PCC 6803 (Synechocystis) and used as bait in pull-down experiments. We retrieved an enzymatically active complex comprising ChlG and the high-light-inducible protein HliD, which associates with the Ycf39 protein, a putative assembly factor for photosystem II, and with the YidC/Alb3 insertase. 2D electrophoresis and immunoblotting also provided evidence for the presence of SecY and ribosome subunits. The isolated complex contained chlorophyll, chlorophyllide, and carotenoid pigments. Deletion of hliD elevated the level of the ChlG substrate, chlorophyllide, more than 6-fold; HliD is apparently required for assembly of FLAG-ChlG into larger complexes with other proteins such as Ycf39. These data reveal a link between chlorophyll biosynthesis and the Sec/YidC-dependent cotranslational insertion of nascent photosystem polypeptides into membranes. We expect that this close physical linkage coordinates the arrival of pigments and nascent apoproteins to produce photosynthetic pigment-protein complexes with minimal risk of accumulating phototoxic unbound chlorophylls.
Differential allocation and deployment of direct and indirect defences by Vicia sepium along elevation gradients
Authors: Rasmann Sergio , Buri Aline , Gallot‐Lavallée Marie , Joaquim Jessica , Purcell Jessica , Pellissier Loïc
Published: March 2014

Dissecting drivers of plant defence investment remains central for understanding the assemblage of communities across different habitats. There is increasing evidence that direct defence strategies against herbivores, including secondary metabolites production, differ along ecological gradients in response to variation in biotic and abiotic conditions. In contrast, intraspecific variation in indirect defences remains unexplored.

Here, we investigated variation in herbivory rate, resistance to herbivores and indirect defences in ant‐attracting Vicia species along the elevation gradient of the Alps. Specifically, we compared volatile organic compounds (VOCs) and ant attraction in high‐ and low‐elevation ecotypes.

Consistent with adaptation to the lower herbivory conditions that we detected at higher elevations in the field, high‐elevation plants were visited by fewer ants and were more susceptible to herbivore attack. In parallel, constitutive volatile organic compound production and subsequent ant attraction were lower in the high‐elevation ecotypes.

We observed an elevation‐driven trade‐off between constitutive and inducible production of VOCs and ant attraction along the environmental cline. At higher elevations, inducible defences increased, while constitutive defence decreased, suggesting that the high‐elevation ecotypes compensate for lower indirect constitutive defences only after herbivore attack.

Synthesis. Overall, direct and indirect defences of plants vary along elevation gradients. Our findings show that plant allocation to defences are subject to trade‐offs depending on local conditions, and point to a feedback mechanism linking local herbivore pressure, predator abundance and the defence investment of plants.
Rethinking the Comparative Perspective on Class and Representation: Evidence from Latin America
Authors: Carnes Nicholas , Lupu Noam
Published: March 2014

Does it matter that working‐class citizens are numerically underrepresented in political offices throughout the world? For decades, the conventional wisdom in comparative politics has been that it does not, that lawmakers from different classes think and behave roughly the same in office. In this article, we argue that this conclusion is misguided. Past research relied on inappropriate measures of officeholders’ class backgrounds, attitudes, and choices. Using data on 18 Latin American legislatures, we show that lawmakers from different classes bring different economic attitudes to the legislative process. Using data on one least likely case, we also show that pre‐voting decisions like sponsoring legislation often differ dramatically along social class lines, even when political parties control higher‐visibility decisions like roll‐call votes. The unequal numerical or descriptive representation of social classes in the world's legislatures has important consequences for the substantive representation of different class interests.
Distinct regulation of tonsillar immune response in virus infection
Authors: Jartti T. , Palomares O. , Waris M. , Tastan O. , Nieminen R. , Puhakka T. , Rückert B. , Aab A. , Vuorinen T. , Allander T. , Vahlberg T. , Ruuskanen O. , Akdis M. , Akdis C. A.
Published: March 2014

Background

The relationships between tonsillar immune responses, and viral infection and allergy are incompletely known.

Objective

To study intratonsillar/nasopharyngeal virus detections and in vivo expressions of T‐cell‐ and innate immune response‐specific cytokines, transcription factors, and type I/II/III interferons in human tonsils.

Methods

Palatine tonsil samples were obtained from 143 elective tonsillectomy patients. Adenovirus, bocavirus‐1, coronavirus, enteroviruses, influenza virus, metapneumovirus, parainfluenza virus, rhinovirus, and respiratory syncytial virus were detected using PCR. The mRNA expression levels of IFN‐α, IFN‐β, IFN‐γ, IL‐10, IL‐13, IL‐17, IL‐28, IL‐29, IL‐37, TGF‐β, FOXP3, GATA3, RORC2, and Tbet were directly analyzed by quantitative RT‐PCR.

Results

Fifty percentage of subjects reported allergy, 59% had ≥1 nasopharyngeal viruses, and 24% had ≥1 intratonsillar viruses. Tonsillar virus detection showed a strong negative association with age; especially rhinovirus or parainfluenza virus detection showed positive association with IFN‐γ and Tbet expressions. IL‐37 expression was positively associated with atopic dermatitis, whereas IFN‐α, IL‐13, IL‐28, and Tbet expressions were negatively associated with allergic diseases. Network analyses demonstrated strongly polarized clusters of immune regulatory (IL‐10, IL‐17, TGF‐β, FOXP3, GATA3, RORC2, Tbet) and antiviral (IFN‐α, IFN‐β, IL‐28, IL‐29) genes. These two clusters became more distinctive in the presence of viral infection or allergy. A negative correlation between antiviral cytokines and IL‐10, IL‐17, IL‐37, FOXP3, and RORC2 was observed only in the presence of viruses, and interestingly, IL‐13 strongly correlated with antiviral cytokines.

Conclusions

Tonsillar cytokine expression is closely related to existing viral infections, age, and allergic illnesses and shows distinct clusters between antiviral and immune regulatory genes.
Paraneoplastic anti‐N‐methyl‐d‐aspartate receptor encephalitis: have you checked the ovaries?
Authors: Cleverly Kirsty , Gambadauro Pietro , Navaratnarajah Ramesan
Published: March 2014

Anti‐N‐methyl‐d‐aspartate receptor encephalitis is an autoimmune disorder that can occur as a paraneoplastic phenomenon related to ovarian teratomas. It is a serious but reversible condition with improved outcomes following prompt tumor removal. We report two cases from our recent experience. In the first case a small poorly described lesion, confirmed as a teratoma only at histology, was managed by laparoscopic oopohorectomy. In the second case a large teratoma was managed by laparoscopic cystectomy. Postoperatively both women made a good recovery. Gynecologists may be called upon to perform ovarian surgery outside of normal surgical indications, in young women who will often lack capacity to consent. Fertility‐sparing ovarian cystectomy is possible in some cases, but will be challenging for small deeply buried tumors. Blind bilateral oophorectomy has been performed successfully in extreme cases. Information of the benefit of ovarian surgery will be essential to the surgeon during preoperative counseling.
Maternal blood pressure and heart rate response to pelvic floor muscle training during pregnancy
Authors: Ferreira Cristine H. , Naldoni Luciane M.V. , Ribeiro Juliana dos Santos , Meirelles Maria Cristina C.C. , Cavalli Ricardo de Carvalho , Bø Kari
Published: March 2014

Objectives

To assess whether maternal blood pressure (BP) and heart rate (HR) change significantly in response to pelvic floor muscle training during pregnancy.

Design

Longitudinal exploratory study with repeated measurements.

Sample

Twenty‐seven nulliparous healthy women of mean age 23.3 years (range 18–36) and mean body mass index 23.4 (range 23.1–29.5).

Methods

Individual supervised pelvic floor muscle training from gestational week 20 till 36 with assessment of BP and HR at gestational weeks 20, 24, 28, 32 and 36.

Main outcome measures

Systolic and diastolic BP was measured before and after each training session and HR was monitored during each session.

Results

Pelvic floor muscle training did not change BP. 77% (n = 21) of participants exceeded 70% of estimated maximum HR during at least one session. The time for exceeding 70% of estimated maximum HR was between 2.2 and 3.2 % of the total exercise session. Increases in BP and HR from gestational weeks 20 till 36 were within normal limits for pregnant women.

Conclusions

Pelvic floor muscle training in nulliparous sedentary pregnant women does not increase BP. It significantly increases HR during the exercise sessions, but only for a limited period of time and with no negative long‐term effect on BP or HR.
Cardiovascular and metabolic responses to tap water ingestion in young humans: does the water temperature matter?
Authors: Girona M. , Grasser E. K. , Dulloo A. G. , Montani J. P.
Published: March 2014

Aim

Drinking water induces short‐term cardiovascular and metabolic changes. These effects are considered to be triggered by gastric distension and osmotic factors, but little is known about the influence of water temperature.

Methods

We determined, in a randomized crossover study, the acute cardiovascular and metabolic responses to 500 mL of tap water at 3 °C (cold), 22 °C (room) and 37 °C (body) in 12 young humans to ascertain an effect of water temperature. We measured continuous beat‐to‐beat haemodynamics, skin blood flux with laser‐Doppler flowmetry and resting energy expenditure by indirect calorimetry starting with a 30‐min baseline followed by a 4‐min drink period and a subsequent 90‐min post‐drink observation.

Results

Ingestion of cold‐ and room‐tempered water led to decreased heart rate (P < 0.01) and double product (P < 0.01), and increased stroke volume (P < 0.05); these effects were not observed with body‐tempered water. Drinking cold‐ and room‐, but not body‐tempered water, led to increased high frequency power of heart rate variability (P < 0.05) and baroreflex sensitivity (P < 0.05). Cold‐ and room‐tempered water increased energy expenditure over 90 min by 2.9% (P < 0.05) and 2.3% (ns), respectively, accompanied by a diminished skin blood flux (P < 0.01), thereby suggesting that both small increases in heat production together with decreased heat loss contribute to warming up the ingested water to intra‐abdominal temperature levels.

Conclusions

Overall, ingestion of cold‐ and room‐, but not body‐tempered water reduced the workload to the heart through a reduction in heart rate and double product which could be mediated by an augmented cardiac vagal tone.
The chequered history of the antiphospholipid syndrome
Authors: Jayakody Arachchillage Deepa , Greaves Mike
Published: March 2014

Consideration of the chronology of advances in medical knowledge can provide useful insights into the pathogenesis, diagnosis and treatment of diseases. The antiphospholipid syndrome is an enigmatic disorder and this is reinforced by the misleading associated terminology, the adoption of which results directly from early discoveries relating to the condition. Thus the target antigen of the causative autoantibodies in antiphospholipid syndrome does not reside on phospholipid, and the frequently associated lupus anticoagulant is not restricted to subjects with systemic lupus erythematosus and, paradoxically, despite causing prolongation of clotting times in vitro it is associated with a pronounced tendency to thrombosis. Recognition of the antiphospholipid syndrome has its origins in the identification of subjects with so‐called biological false‐positive serological reactions for syphilis in the middle years of the last century. Since that time there have been considerable advances in our understanding of the pathogenesis of the disease and the clinical manifestations and associations, improved diagnostic accuracy and an evolving evidence base for optimal therapy. However many gaps in our knowledge remain.
A pilot study of plasma metabolomic patterns from patients treated with ketamine for bipolar depression: evidence for a response‐related difference in mitochondrial networks
Authors: Villaseñor A , Ramamoorthy A , Silva dos Santos M , Lorenzo M P , Laje G , Zarate C , Barbas C , Wainer I W
Published: March 2014

Background and Purpose

(R,S)‐ketamine produces rapid and significant antidepressant effects in approximately 65% of patients suffering from treatment‐resistant bipolar depression (BD). The genetic, pharmacological and biochemical differences between ketamine responders and non‐responders have not been identified. The purpose of this study was to employ a metabolomics approach, a global, non‐targeted determination of endogenous metabolic patterns, to identify potential markers of ketamine response and non‐response.

Experimental Approach

Plasma samples from 22 BD patients were analyzed to produce metabolomic patterns. The patients had received ketamine in a placebo‐controlled crossover study and the samples were obtained 230 min post‐administration at which time the patients were categorized as responders or non‐responders. Matching plasma samples from the placebo arm of the study were also analysed. During the study, the patients were maintained on either lithium or valproate.

Key Results

The metabolomic patterns were significantly different between the patients maintained on lithium and those maintained on valproate, irrespective of response to ketamine. In the patients maintained on lithium, 18 biomarkers were identified. In responders, lysophosphatidylethanolamines (4) and lysophosphatidylcholines (9) were increased relative to non‐responders.

Conclusions and Implications

The results indicate that the differences between patients who respond to ketamine and those who do not are due to alterations in the mitochondrial β‐oxidation of fatty acids. These differences were not produced by ketamine administration. The data indicate that pretreatment metabolomics screening may be a guide to the prediction of response and a potential approach to the individualization of ketamine therapy.

Linked Articles

This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue‐8
Recent advances in the pathophysiology and management of eosinophilic oesophagitis
Authors: Epstein J. , Warner J. O.
Published: March 2014

Eosinophilic oesophagitis is an increasingly recognized allergic gastrointestinal disease, which is becoming more common. Although the average age at diagnosis is 30–50 years, it often affects very young children and carries significant long‐term morbidity. While our understanding of its pathophysiology is accumulating, the precise pathways by which the disease arises remain unclear. There are inconsistencies in its diagnosis and definition, and a drive towards international standardization is underway. Current methods for diagnosis and monitoring are relatively invasive, and controversies surround their interpretation. Management strategies are imperfect and involve burdensome long‐term dietary exclusions, or drug treatments with uncertain efficacy or serious side‐effects. It is the focus of a rapidly increasing body of research, the latest insights from which are systematically presented in this review.
Grass pollen allergens globally: the contribution of subtropical grasses to burden of allergic respiratory diseases
Authors: Davies J. M.
Published: March 2014

Grass pollens of the temperate (Pooideae) subfamily and subtropical subfamilies of grasses are major aeroallergen sources worldwide. The subtropical Chloridoideae (e.g. Cynodon dactylon; Bermuda grass) and Panicoideae (e.g. Paspalum notatum; Bahia grass) species are abundant in parts of Africa, India, Asia, Australia and the Americas, where a large and increasing proportion of the world's population abide. These grasses are phylogenetically and ecologically distinct from temperate grasses. With the advent of global warming, it is conceivable that the geographic distribution of subtropical grasses and the contribution of their pollen to the burden of allergic rhinitis and asthma will increase. This review aims to provide a comprehensive synthesis of the current global knowledge of (i) regional variation in allergic sensitivity to subtropical grass pollens, (ii) molecular allergenic components of subtropical grass pollens and (iii) allergic responses to subtropical grass pollen allergens in relevant populations. Patients from subtropical regions of the world show higher allergic sensitivity to grass pollens of Chloridoideae and Panicoideae grasses, than to temperate grass pollens. The group 1 allergens are amongst the allergen components of subtropical grass pollens, but the group 5 allergens, by which temperate grass pollen extracts are standardized for allergen content, appear to be absent from both subfamilies of subtropical grasses. Whilst there are shared allergenic components and antigenic determinants, there are additional clinically relevant subfamily‐specific differences, at T‐ and B‐cell levels, between pollen allergens of subtropical and temperate grasses. Differential immune recognition of subtropical grass pollens is likely to impact upon the efficacy of allergen immunotherapy of patients who are primarily sensitized to subtropical grass pollens. The literature reviewed herein highlights the clinical need to standardize allergen preparations for both types of subtropical grass pollens to achieve optimal diagnosis and treatment of patients with allergic respiratory disease in subtropical regions of the world.
The emerging era of pharmacogenomics: current successes, future potential, and challenges
Authors: Lee J.W. , Aminkeng F. , Bhavsar A.P. , Shaw K. , Carleton B.C. , Hayden M.R. , Ross C.J.D.
Published: March 2014

The vast range of genetic diversity contributes to a wonderful array of human traits and characteristics. Unfortunately, a consequence of this genetic diversity is large variability in drug response between people, meaning that no single medication is safe and effective in everyone. The debilitating and sometimes deadly consequences of adverse drug reactions (ADRs) are a major and unmet problem of modern medicine. Pharmacogenomics can uncover associations between genetic variation and drug safety and has the potential to predict ADRs in individual patients. Here we review pharmacogenomic successes leading to changes in clinical practice, as well as clinical areas probably to be impacted by pharmacogenomics in the near future. We also discuss some of the challenges, and potential solutions, that remain for the implementation of pharmacogenomic testing into clinical practice for the significant improvement of drug safety.
Connectivity Conservation and Endangered Species Recovery: A Study in the Challenges of Defining Conservation‐Reliant Species
Authors: Carroll Carlos , Rohlf Daniel J. , Li Ya‐Wei , Hartl Brett , Phillips Michael K. , Noss Reed F.
Published: March 2014

Many species listed under the US Endangered Species Act (ESA) face continuing threats and will require intervention to address those threats for decades. These species, which have been termed conservation‐reliant, pose a challenge to the ESA's mandate for recovery of self‐sustaining populations. Most references to conservation‐reliant species by federal agencies involve the restoration of population connectivity. However, the diverse threats to connectivity faced by different species have contrasting implications in the context of the ESA's mandate. For species facing long‐term threats from invasive species or climate change, restoration of natural dispersal may not be technically feasible in the foreseeable future. For other species, restoration of natural dispersal is feasible, but carries economic and political cost. Federal agencies have used a broad definition of conservation reliance to justify delisting of species in the latter group even if they remain dependent on artificial translocation. Distinguishing the two groups better informs policy by distinguishing the technical challenges posed by novel ecological stressors from normative questions such as the price society is willing to pay to protect biodiversity, and the degree to which we should grow accustomed to direct human intervention in species’ life cycles as a component of conservation in the Anthropocene Epoch.
Effects of resistance training under hypoxic conditions on muscle hypertrophy and strength
Authors: Kurobe Kazumichi , Huang Zhong , Nishiwaki Masato , Yamamoto Masayoshi , Kanehisa Hiroaki , Ogita Futoshi
Published: April 2014

It has been reported that exercise under hypoxic conditions elevates acute growth hormone secretion after exercise compared with that under normoxic conditions. This study examined the influence of resistance training under moderate hypoxic conditions on muscle thickness, strength and hormonal responses. Thirteen healthy men were assigned into two groups matched for physical fitness level and then randomized into two groups that performed exercise under normoxic (FiO2 = 20·9%) or hypoxic (FiO2 = 12·7%) conditions. Three sets of elbow extensions with unilateral arm were performed to exhaustion at a workload of a 10 repetition maximum with 1‐minute intervals for 3 days per week for 8 weeks. The thickness of the biceps and triceps brachii was determined using B‐mode ultrasound before and after training. Blood sampling was carried out before and after exercise, as well as during the first and last training sessions. Increase in the thickness of the triceps brachii in trained arm was significantly greater in the hypoxic group than in the normoxic group. The 10 repetition maximum was significantly increased not only in the trained arm but also in the untrained arm in both groups. Serum growth hormone concentrations after exercise were significantly higher in the hypoxic group than in the normoxic group on both the first and last training sessions. These findings suggest that hypoxic resistance training elicits more muscle hypertrophy associated with a higher growth hormone secretion, but that the greater muscle hypertrophy did not necessarily contribute a greater gain of muscle strength.
Uncertainty, priors, autocorrelation and disparate data in downscaling of species distributions
Authors: Keil Petr , Wilson Adam M. , Jetz Walter
Published: March 2014

Aim

We provide a step‐by‐step demonstration of how a map of species' detections at continental extent can be downscaled to a fine‐grain map of occurrence probabilities using a two‐scale hierarchicalBayesian modelling (HBM). The method requires fine‐grain environmental data, but it does not require fine‐grain data on species detections. We demonstrate how it can incorporate spatial autocorrelation (SAC) and informative priors based on known habitat preferences, and how it can provide maps of uncertainty about the downscaled predictions.

Location

USA.

Methods

We used range map and point record data on the distribution ofAmerican three‐toed woodpecker (Picoides dorsalis,Baird 1858) to produce a reliable coarse‐grain (160 km × 160 km) map of the species' presences and absences. We developed anHBMcombining coarse‐grain information with fine‐grain (20 km × 20 km) environmental data to predict probabilities of occurrence at the fine grain together with 95% prediction intervals. The model incorporatedSACin the form of conditional autoregressive (CAR) random effects. It also incorporated prior knowledge on habitat preferences in the form of prior distribution of parameters. We evaluated the predictions using 751 well‐surveyed fine‐grain cells.

Results

OurHBMproduced reliable fine‐grain probabilities of occurrence that matched the detections and non‐detections in the 751 validation cells well (Nagelkerke'sR2 = 0.69,AUC = 0.93). By mapping the uncertainty in the downscaled predictions, we identified areas of low uncertainty and high occurrence probability, as well as large areas of high prediction uncertainty. Mapping the autocorrelation term enabled to identify areas of likely spurious observations.

Main conclusions

We demonstrate how hierarchical downscaling enables estimation of species distributions at grains finer than the grain of the original data. The approach can integrate various types of information on distribution and biology in a single statistical framework, and it enables propagating and mapping prediction uncertainty. Yet there are also computational challenges for large datasets.
Can coarse‐grain patterns in insect atlas data predict local occupancy?
Authors: Barwell Louise J. , Azaele Sandro , Kunin William E. , Isaac Nick J. B.
Published: March 2014

Aim

Species atlases provide an economical way to collect data with national coverage, but are typically too coarse‐grained to monitor fine‐grain patterns in rarity, distribution and abundance. We test the performance of ten downscaling models in extrapolating occupancy across two orders of magnitude. To provide a greater challenge to downscaling models, we extend previous downscaling tests with plants to highly mobile insect taxa (Odonata) with a life history that is tied to freshwater bodies for reproduction. We investigate the species‐level correlates of predictive accuracy for the best performing model to understand whether traits driving spatial structure can cause interspecific variation in downscaling success.

Location

Mainland Britain.

Methods

Occupancy data for 38 British Odonata species were extracted from the Dragonfly Recording Network (DRN). Occupancy at grains ≥ 100 km2 was used as training data to parameterize ten downscaling models. Predicted occupancy at the 25, 4 and 1 km2 grains was compared to observed data at corresponding grains. Model predictive error was evaluated across species and grains.

Main conclusions

The Hui model gave the most accurate downscaling predictions across 114 species:grain combinations and the best predictions for 14 of the 38 species, despite being the only model using information at a single spatial grain. The occupancy–area relationship was sigmoidal in shape for most species. Species' distribution type and dispersal ability explained over half of the variation in downscaling predictive error at the species level. Species with a climatic range limit in Britain were poorly predicted compared with other distribution types, and high dispersal ability was associated with relatively poor downscaling predictions. Our results suggest that downscaling models, using widely available coarse‐grain atlas data, provide reasonable estimates of fine‐grain occupancy, even for insect taxa with strong spatial structure. Linking species‐level traits with predictive accuracy reveals general principles about when downscaling will be successful.
Severe infantile epileptic encephalopathy due to mutations in PLCB1: expansion of the genotypic and phenotypic disease spectrum
Authors: Ngoh Adeline , McTague Amy , Wentzensen Ingrid M , Meyer Esther , Applegate Carolyn , Kossoff Eric H , Batista Denise A , Wang Tao , Kurian Manju A
Published: March 2014

Homozygous deletions of chromosome 20p12.3, disrupting the promoter region and first three coding exons of the phospholipase C β1 gene (PLCB1), have previously been described in two reports of early infantile epileptic encephalopathy (EIEE). Both children were born to consanguineous parents, one presented with infantile spasms, the other with migrating partial seizures of infancy. We describe an infant presenting with severe intractable epilepsy (without a specific EIEE electroclinical syndrome diagnosis) and neurodevelopmental delay associated with compound heterozygous mutations in PLCB1. A case note review and molecular genetic investigations were performed for a child, approximately 10 months of age, admitted to Johns Hopkins University Hospital for developmental delay and new‐onset seizures. The patient presented at 6 months of age with developmental delay, followed by the onset of intractable, focal, and generalized seizures associated with developmental regression from 10 months of age. Presently, at 2 years of age, the child has severe motor and cognitive delays. Diagnostic microarray revealed a heterozygous 476kb deletion of 20p12.3 (encompassing PLCB1), which was also detected in the mother. The genomic breakpoints for the heterozygous deletion were determined. In order to investigate the presence of a second PLCB1 mutation, direct Sanger sequencing of the coding region and flanking intronic regions was undertaken, revealing a novel heterozygous intron 1 splice site variant (c.99+1G>A) in both the index individual and the father. Advances in molecular genetic testing have greatly improved diagnostic rates in EIEE, and this report further confirms the important role of microarray investigation in this group of disorders. PLCB1‐EIEE is now reported in a number of different EIEE phenotypes and our report provides further evidence for phenotypic pleiotropy encountered in early infantile epilepsy syndromes.
Can biotic interactions cause allopatry? Niche models, competition, and distributions of South American mouse opossums
Authors: Gutiérrez Eliécer E. , Boria Robert A. , Anderson Robert P.
Published: April 2014

Based on our own empirical data and a literature review, we explore the possibility that biotic interactions, specifically competition, might be responsible for creating, and/or maintaining, geographic isolation. Ecological niche modeling was first used to test whether the distributions of 2 species of Neotropical marsupials (Marmosa robinsoni and M. xerophila) fit the predicted geographic pattern of competitive exclusion: one species predominates in areas environmentally suitable for both species along real contact zones. Secondly, we examined the connectivity among populations of each species, interpreted in the light of the niche models. The results show predominance of M. xerophila along its contact zone with M. robinsoni in the Península de Paraguaná in northwestern Venezuela. There, M. robinsoni has an extremely restricted distribution despite climatic conditions suitable for both species across the peninsula and its isthmus. The latter two results suggest that M. xerophila may be responsible for the geographic isolation of the peninsular populations of M. robinsoni with respect to other populations of the latter species in northwestern Venezuela. These results may represent an example of allopatry caused, or at least maintained, by competition. Our results and a review of numerous studies in which biotic interactions restrict species distributions (including at the continental scale) support a previously overlooked phenomenon: biotic interactions can isolate populations of a species. We propose 2 general mechanisms, intrusion and contraction, to classify allopatric conditions caused by various classes of biotic interactions. We present a necessary modification of the concept of ecological vicariance to include biotic interactions as possible vicariant agents regardless of whether genetic differentiation occurs or not.
Migration, self‐selection and income distributions
Authors: Xing C.
Published: March 2014

Self‐selection in rural–urban migration is examined using three datasets from rural and urban China in 2002. We construct a migrant sample including both migrants who converted their hukou status from rural to urban (permanent migrants) and those who did not (temporary migrants). We find a strong positive selection for permanent migrants, but the selection for temporary migrants is ambiguous. We reach these conclusions by comparing migrants' counterfactual wage densities, assuming they are paid as rural local workers, to actual wage densities of rural local workers. Our results imply that permanent migration has negative effects on rural human capital accumulation and income levels.
Glucocorticoid receptor deletion from the dorsal raphé nucleus of mice reduces dysphoria‐like behavior and impairs hypothalamic‐pituitary‐adrenocortical axis feedback inhibition
Authors: Vincent Melanie Y. , Jacobson Lauren
Published: March 2014

Glucocorticoids can cause depression and anxiety. Mechanisms for glucocorticoid effects on mood are largely undefined. The dorsal raphé nucleus (DRN) produces the majority of serotonin in the brain, and expresses glucocorticoid receptors (GR). Because we previously showed that antidepressants used to treat depression and anxiety decrease DRN GR expression, we hypothesized that deleting DRN GR would have anxiolytic‐ and antidepressant‐like effects. We also hypothesized that DRN GR deletion would disinhibit activity of the hypothalamic–pituitary–adrenal (HPA) axis. Adeno‐associated virus pseudotype AAV2/9 expressing either Cre recombinase (DRNGRKO mice) or GFP (DRN‐GFP mice) was injected into the DRN of floxed GR mice to test these hypotheses. Three weeks after injection, mice underwent 21 days of social defeat or control handling and were tested for anxiety‐like behavior (open‐field test, elevated‐plus maze), depression‐like behavior [sucrose preference, forced‐swim test (FST), tail‐suspension test (TST)], social interaction, and circadian and stress‐induced HPA activity. DRN GR deletion decreased anxiety‐like behavior in control but not in defeated mice. DRN GR deletion decreased FST and tended to decrease TST despair‐like behavior in both control and defeated mice, but did not affect sucrose preference. Exploration of social (a novel mouse) as well as neutral (an empty box) targets was increased in DRNGRKO mice, suggesting that DRN GR deletion also promotes active coping. DRN GR deletion increased stress‐induced HPA activity without strongly altering circadian HPA activity. We have shown a novel role for DRN GR to mediate anxiety‐ and despair‐like behavior and to regulate HPA negative feedback during acute stress.
Association of moyamoya disease with thyroid autoantibodies and thyroid function: a case−control study and meta‐analysis
Authors: Lei C. , Wu B. , Ma Z. , Zhang S. , Liu M.
Published: March 2014

Background and purpose

Evidence suggests that elevated thyroid function and elevated levels of thyroid autoantibodies are associated with risk of moyamoya disease (MMD). Therefore a meta‐analysis of all available evidence was performed, including unpublished data from our own center, in order to assess this association.

Methods

Major literature databases were reviewed without language restrictions to identify studies examining the association between MMD and thyroid function or thyroid autoantibodies. These data were combined with those from our own prospective study. This study involved consecutively recruited patients with MMD and two groups of age‐matched control patients: patients with non‐MMD stroke and healthy individuals. The groups were compared in terms of serum triiodothyronine (T3), thyroxine (T4), free T4, free T3, thyroid stimulating hormone, anti‐thyroperoxidase antibody and anti‐thyroglobulin antibody.

Results

Our prospective study involved 28 patients with MMD, 28 age‐matched patients with non‐MMD stroke and 28 age‐matched healthy control participants. The results showed an association between risk of MMD and elevated thyroid autoantibodies [odds ratio (OR) 9.00, 95% confidence interval (CI) 1.03–78.94] but not between risk of MMD and elevated thyroid function (OR 5.87, 95% CI 0.64–53.93). Meta‐analysis of our data with findings from the literature further supported the association with elevated thyroid autoantibodies (OR 8.77, 95% CI 4.45–17.29) and indicated an association with elevated thyroid function (OR 9.74, 95% CI 2.18–43.49).

Conclusions

Evidence strongly suggests that elevated thyroid autoantibodies and elevated thyroid function are independently associated with MMD. These clinical variables may require regular monitoring in patients with MMD.
Muscle atrophy in chronic inflammatory demyelinating polyneuropathy: a computed tomography assessment
Authors: Ohyama K. , Koike H. , Katsuno M. , Takahashi M. , Hashimoto R. , Kawagashira Y. , Iijima M. , Adachi H. , Watanabe H. , Sobue G.
Published: March 2014

Background and purpose

Muscle atrophy is generally mild in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) compared with the severity and duration of the muscle weakness. Muscle atrophy was evaluated using computed tomography (CT) in patients with CIDP.

Methods

Thirty‐one patients with typical CIDP who satisfied the diagnostic criteria for the definite CIDP classification proposed by the European Federation of Neurological Societies and the Peripheral Nerve Society were assessed. The clinicopathological findings in patients with muscle atrophy were also compared with those in patients without atrophy.

Results

Computed tomography evidence was found of marked muscle atrophy with findings suggestive of fatty degeneration in 11 of the 31 patients with CIDP. CT‐assessed muscle atrophy was in the lower extremities, particularly in the ankle plantarflexor muscles. Muscle weakness, which reflects the presence of muscle atrophy, tended to be more pronounced in the lower extremities than in the upper extremities in patients with muscle atrophy, whereas the upper and lower limbs tended to be equally affected in patients without muscle atrophy. Nerve conduction examinations revealed significantly greater reductions in compound muscle action potential amplitudes in the tibial nerves of patients with muscle atrophy. Sural nerve biopsy findings were similar in both groups. The functional prognoses after immunomodulatory therapies were significantly poorer amongst patients with muscle atrophy.

Conclusions

Muscle atrophy was present in a subgroup of patients with CIDP, including patients with a typical form of the disease. These patients tended to demonstrate predominant motor impairments of the lower extremities and poorer functional prognoses.
Statins are associated with decreased mortality risk after status epilepticus
Authors: Sierra‐Marcos A. , Alvarez V. , Faouzi M. , Burnand B. , Rossetti A. O.
Published: March 2014

Background and purpose

Statins display anti‐inflammatory and anti‐epileptogenic properties in animal models, and may reduce the epilepsy risk in elderly humans; however, a possible modulating role on outcome in patients with status epilepticus (SE) has not been assessed.

Methods

This cohort study was based on a prospective registry including all consecutive adults with incident SE treated in our center between April 2006 and September 2012. SE outcome was categorized at hospital discharge into ‘return to baseline’, ‘new disability’ and ‘mortality’. The role of potential predictors, including statins treatment on admission, was evaluated using a multinomial logistic regression model.

Results

Amongst 427 patients identified, information on statins was available in 413 (97%). Mean age was 60.9 (±17.8) years; 201 (49%) were women; 211 (51%) had a potentially fatal SE etiology; and 191 (46%) experienced generalized‐convulsive or non‐convulsive SE in coma. Statins (simvastatin, atorvastatin or pravastatin) were prescribed prior to admission in 76 (18%) subjects, mostly elderly. Whilst 208 (50.4%) patients returned to baseline, 58 (14%) died. After adjustment for established SE outcome predictors (age, etiology, SE severity score), statins correlated significantly with lower mortality (relative risk ratio 0.38, P = 0.046).

Conclusion

This study suggests for the first time that exposure to statins before an SE episode is related to its outcome, involving a possible anti‐epileptogenic role. Other studies are needed to confirm this intriguing finding.