bluuebunny/crossref_metadata_2025 huggingface dataset:
Myo1c binding to submembrane actin mediates insulin-induced tethering of GLUT4 vesicles
Authors: Boguslavsky Shlomit , Chiu Tim , Foley Kevin P. , Osorio-Fuentealba Cesar , Antonescu Costin N. , Bayer K. Ulrich , Bilan Philip J. , Klip Amira
Published: August 2012

GLUT4-containing vesicles cycle between the plasma membrane and intracellular compartments. Insulin promotes GLUT4 exocytosis by regulating GLUT4 vesicle arrival at the cell periphery and its subsequent tethering, docking, and fusion with the plasma membrane. The molecular machinery involved in GLUT4 vesicle tethering is unknown. We show here that Myo1c, an actin-based motor protein that associates with membranes and actin filaments, is required for insulin-induced vesicle tethering in muscle cells. Myo1c was found to associate with both mobile and tethered GLUT4 vesicles and to be required for vesicle capture in the total internal reflection fluorescence (TIRF) zone beneath the plasma membrane. Myo1c knockdown or overexpression of an actin binding–deficient Myo1c mutant abolished insulin-induced vesicle immobilization, increased GLUT4 vesicle velocity in the TIRF zone, and prevented their externalization. Conversely, Myo1c overexpression immobilized GLUT4 vesicles in the TIRF zone and promoted insulin-induced GLUT4 exposure to the extracellular milieu. Myo1c also contributed to insulin-dependent actin filament remodeling. Thus we propose that interaction of vesicular Myo1c with cortical actin filaments is required for insulin-mediated tethering of GLUT4 vesicles and for efficient GLUT4 surface delivery in muscle cells.
RhoA activation during polarization and cytokinesis of the early Caenorhabditis elegans embryo is differentially dependent on NOP-1 and CYK-4
Authors: Tse Yu Chung , Werner Michael , Longhini Katrina M. , Labbe Jean-Claude , Goldstein Bob , Glotzer Michael
Published: August 2012

The GTPase RhoA is a central regulator of cellular contractility in a wide variety of biological processes. During these events, RhoA is activated by guanine nucleotide exchange factors (GEFs). These molecules are highly regulated to ensure that RhoA activation occurs at the proper time and place. During cytokinesis, RhoA is activated by the RhoGEF ECT-2. In human cells, ECT-2 activity requires its association with CYK-4, which is a component of the centralspindlin complex. In contrast, in early Caenorhabditis elegans embryos, not all ECT-2–dependent functions require CYK-4. In this study, we identify a novel protein, NOP-1, that functions in parallel with CYK-4 to promote RhoA activation. We use mutations in nop-1 and cyk-4 to dissect cytokinesis and cell polarization. NOP-1 makes a significant, albeit largely redundant, contribution to cytokinesis. In contrast, NOP-1 is required for the preponderance of RhoA activation during the establishment phase of polarization.
Regulation of axonal growth and neuromuscular junction formation by neuronal phosphatase and tensin homologue signaling
Authors: Li Pan P. , Peng H. Benjamin
Published: August 2012

During the development of the vertebrate neuromuscular junction (NMJ), motor axon tips stop growing after contacting muscle and transform into presynaptic terminals that secrete the neurotransmitter acetylcholine and activate postsynaptic ACh receptors (AChRs) to trigger muscle contraction. The neuron-intrinsic signaling that retards axonal growth to facilitate stable nerve–muscle interaction and synaptogenesis is poorly understood. In this paper, we report a novel function of presynaptic signaling by phosphatase and tensin homologue (PTEN) in mediating a growth-to-synaptogenesis transition in neurons. In Xenopus nerve–muscle cocultures, axonal growth speed was halved after contact with muscle, when compared with before contact, but when cultures were exposed to the PTEN blocker bisperoxo (1,10-phenanthroline) oxovanadate, axons touching muscle grew ∼50% faster than their counterparts in control cultures. Suppression of neuronal PTEN expression using morpholinos or the forced expression of catalytically inactive PTEN in neurons also resulted in faster than normal axonal advance after contact with muscle cells. Significantly, interference with PTEN by each of these methods also led to reduced AChR clustering at innervation sites in muscle, indicating that disruption of neuronal PTEN signaling inhibited NMJ assembly. We thus propose that PTEN-dependent slowing of axonal growth enables the establishment of stable nerve–muscle contacts that develop into NMJs.
Cdc42p regulation of the yeast formin Bni1p mediated by the effector Gic2p
Authors: Chen Hsin , Kuo Chun-Chen , Kang Hui , Howell Audrey S. , Zyla Trevin R. , Jin Michelle , Lew Daniel J.
Published: August 2012

Actin filaments are dynamically reorganized to accommodate ever-changing cellular needs for intracellular transport, morphogenesis, and migration. Formins, a major family of actin nucleators, are believed to function as direct effectors of Rho GTPases, such as the polarity regulator Cdc42p. However, the presence of extensive redundancy has made it difficult to assess the in vivo significance of the low-affinity Rho GTPase–formin interaction and specifically whether Cdc42p polarizes the actin cytoskeleton via direct formin binding. Here we exploit a synthetically rewired budding yeast strain to eliminate the redundancy, making regulation of the formin Bni1p by Cdc42p essential for viability. Surprisingly, we find that direct Cdc42p–Bni1p interaction is dispensable for Bni1p regulation. Alternative paths linking Cdc42p and Bni1p via “polarisome” components Spa2p and Bud6p are also collectively dispensable. We identify a novel regulatory input to Bni1p acting through the Cdc42p effector, Gic2p. This pathway is sufficient to localize Bni1p to the sites of Cdc42p action and promotes a polarized actin organization in both rewired and wild-type contexts. We suggest that an indirect mechanism linking Rho GTPases and formins via Rho effectors may provide finer spatiotemporal control for the formin-nucleated actin cytoskeleton.
Improved gap size estimation for scaffolding algorithms
Authors: Sahlin Kristoffer , Street Nathaniel , Lundeberg Joakim , Arvestad Lars
Published: August 2012

Motivation: One of the important steps of genome assembly is scaffolding, in which contigs are linked using information from read-pairs. Scaffolding provides estimates about the order, relative orientation and distance between contigs. We have found that contig distance estimates are generally strongly biased and based on false assumptions. Since erroneous distance estimates can mislead in subsequent analysis, it is important to provide unbiased estimation of contig distance.

Results: In this article, we show that state-of-the-art programs for scaffolding are using an incorrect model of gap size estimation. We discuss why current maximum likelihood estimators are biased and describe what different cases of bias we are facing. Furthermore, we provide a model for the distribution of reads that span a gap and derive the maximum likelihood equation for the gap length. We motivate why this estimate is sound and show empirically that it outperforms gap estimators in popular scaffolding programs. Our results have consequences both for scaffolding software, structural variation detection and for library insert-size estimation as is commonly performed by read aligners.

Availability: A reference implementation is provided at https://github.com/SciLifeLab/gapest

Supplementary information:  Supplementary data are availible at Bioinformatics online.

Contact:  ksahlin@csc.kth.se
Identification of trans-acting siRNAs and their regulatory cascades in grapevine
Authors: Zhang Changqing , Li Guangping , Wang Jin , Fang Jinggui
Published: August 2012

Motivation:  Trans-acting small interfering RNAs (ta-siRNAs) play an essential role in the regulation of plant gene expression, but relevant reports are still limited. Bioinformatic analyses indicate that many ta-siRNA-producing loci (TASs) are present in plants, implying the existence of as yet undiscovered ta-siRNAs and related regulatory pathways. To expand our knowledge of these plant gene regulators, we applied high-throughput computational and experimental methods to grapevine (Vitis vinifera L.).

Results: Based on bioinformatic predictions, we identified 49 TASs from 49 055 small RNA clusters. Using RNA degradome analysis, we experimentally validated 5 TASs, 22 ta-siRNAs and 37 ta-siRNA targets. The cis-activities of ta-siRNAs were also confirmed, which suggested an inactive mechanism of TAS transcription, and a produced mechanism of multiple forms of small RNA from same TAS. We examined the conservation of newly identified ta-siRNA regulatory cascades and found that while the cascade related to vviTAS3 was conserved, cascades related to vviTAS7, vviTAS8, vviTAS9 and vviTAS10 were grape-specific. These results broaden the known scope of ta-siRNA regulation.

Contact:zhang_chq2002@sohu.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Qualimap: evaluating next-generation sequencing alignment data
Authors: García-Alcalde Fernando , Okonechnikov Konstantin , Carbonell José , Cruz Luis M. , Götz Stefan , Tarazona Sonia , Dopazo Joaquín , Meyer Thomas F. , Conesa Ana
Published: August 2012

Motivation: The sequence alignment/map (SAM) and the binary alignment/map (BAM) formats have become the standard method of representation of nucleotide sequence alignments for next-generation sequencing data. SAM/BAM files usually contain information from tens to hundreds of millions of reads. Often, the sequencing technology, protocol and/or the selected mapping algorithm introduce some unwanted biases in these data. The systematic detection of such biases is a non-trivial task that is crucial to drive appropriate downstream analyses.

Results: We have developed Qualimap, a Java application that supports user-friendly quality control of mapping data, by considering sequence features and their genomic properties. Qualimap takes sequence alignment data and provides graphical and statistical analyses for the evaluation of data. Such quality-control data are vital for highlighting problems in the sequencing and/or mapping processes, which must be addressed prior to further analyses.

Availability: Qualimap is freely available from http://www.qualimap.org.

Contact:  aconesa@cipf.es

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Community N2 fixation and Trichodesmium spp. abundance along longitudinal gradients in the eastern subtropical North Atlantic
Authors: Fernández Ana , Graña Rocío , Mouriño-Carballido Beatriz , Bode Antonio , Varela Manuel , Domínguez-Yanes J. Francisco , Escánez José , de Armas Demetrio , Marañón Emilio
Published: August 2012

Fernández, A., Graña, R., Mouriño-Carballido, B., Bode, A., Varela, M., Domínguez-Yanes, J. F., Escánez, J., de Armas, D., and Marañón, E. 2013. Community N2 fixation and Trichodesmium spp. abundance along longitudinal gradients in the eastern subtropical North Atlantic. – ICES Journal of Marine Science, 70:223–231. We have determined planktonic community N2 fixation, Trichodesmium abundance, the concentration and vertical diffusive flux of phosphate, and satellite-derived estimates of atmospheric concentration of dust along two longitudinal transects in the eastern subtropical North Atlantic during November 2007 and from April–May 2008. Trichodesmium abundance was particularly low (<3 trichome l−1) during the spring 2008 cruise, when low sea surface temperatures were recorded and vertical stratification was less marked. However, community N2 fixation was always measurable, albeit low compared with other regions of the tropical Atlantic. The average, vertically-integrated N2 fixation rate was 1.20 ± 0.48 µmol N m−2 d−1 in autumn 2007 and 8.31 ± 3.31 µmol N m−2 d−1 in spring 2008. The comparison of these rates of diazotrophy with the observed Trichodesmium abundances suggests that other, presumably unicellular, diazotrophs must have contributed significantly to community N2 fixation, at least during the spring 2008 cruise. Satellite data of atmospheric dust concentration suggested similar rates of atmospheric deposition during the two surveys. In contrast, vertical diffusive fluxes of phosphate were 5-fold higher in spring than in autumn (14.2 ± 12.1 µmol P m−2 d−1 and 2.8 ± 2.6 µmol P m−2 d−1, respectively), which may have stimulated N2 fixation. These findings agree with the growing view that N2 fixation is a more widespread process than the distribution of Trichodesmium alone may suggest. Our data also suggest a role for phosphorus supply in controlling the local variability of diazotrophic activity in a region subject to relatively high atmospheric inputs of iron.
Piriformis Syndrome Surgery Causing Severe Sciatic Nerve Injury
Authors: Justice Phillip E. , Katirji Bashar , Preston David C. , Grossman Gerald E.
Published: August 2012

Piriformis syndrome is a controversial entrapment neuropathy in which the sciatic nerve is thought to be compressed by the piriformis muscle. Two patients developed severe left sciatic neuropathy after piriformis muscle release. One had a total sciatic nerve lesion, whereas the second had a predominantly high common peroneal nerve lesion. Follow-up studies showed reinnervation of the hamstrings only. We conclude that piriformis muscle surgery may be hazardous and result in devastating sciatic nerve injury.
Focal Hypokalemic Paralysis
Authors: Negrotto Laura , Barroso Fabio A.
Published: August 2012

Hypokalemia is one of the most frequent electrolytic disturbances encountered in clinical practice. It usually presents with symmetrical generalized muscle weakness and, on occasions, with arrhythmias.

There are scarce reports of cases presenting with asymmetric or focal weakness in the literature and no systematic reviews on the subject. Therefore, our aim is to describe 2 cases of hypokalemic paralysis that presented as monoparesis and to review the literature on focal hypokalemic paralysis.

Hypokalemic paralysis is usually reversible. However, it can be fatal if the diagnosis and treatment are delayed. It is important to take into account this presentation because failure to recognize it could lead to misdiagnosis, delaying the adequate treatment.
Diverse circular ssDNA viruses discovered in dragonflies (Odonata: Epiprocta)
Authors: Rosario Karyna , Dayaram Anisha , Marinov Milen , Ware Jessica , Kraberger Simona , Stainton Daisy , Breitbart Mya , Varsani Arvind
Published: August 2012

Viruses with circular ssDNA genomes that encode a replication initiator protein (Rep) are among the smallest viruses known to infect both eukaryotic and prokaryotic organisms. In the past few years an overwhelming diversity of novel circular Rep-encoding ssDNA (CRESS-DNA) viruses has been unearthed from various hosts and environmental sources. Since there is limited information regarding CRESS-DNA viruses in invertebrates, this study explored the diversity of CRESS-DNA viruses circulating among insect populations by targeting dragonflies (Epiprocta), top insect predators that accumulate viruses from their insect prey over space and time. Using degenerate PCR and rolling circle amplification coupled with restriction digestion, 17 CRESS-DNA viral genomes were recovered from eight different dragonfly species collected in tropical and temperate regions. Nine of the genomes are similar to cycloviruses and represent five species within this genus, suggesting that cycloviruses are commonly associated with insects. Three of the CRESS-DNA viruses share conserved genomic features with recently described viruses similar to the mycovirus Sclerotinia sclerotiorum hypovirulence-associated DNA virus 1, leading to the proposal of the genus Gemycircularvirus. The remaining viruses are divergent species representing four novel CRESS-DNA viral genera, including a gokushovirus-like prokaryotic virus (microphage) and three eukaryotic viruses with Reps similar to circoviruses. The novelty of CRESS-DNA viruses identified in dragonflies using simple molecular techniques indicates that there is an unprecedented diversity of ssDNA viruses among insect populations.
'Out' in The Valley
Authors: Forsyth Ann
Published: August 2012

Building on previous work by Castells, and Adler and Brenner, I explore the public character of a lesbian concentration in the Connecticut River Valley region of Massachusetts. From the late 1980s this area has gained national media attention for its lesbian population. Using a number of data sources I examine how lesbian residences and services are distributed in the Valley. I find a strong service core in the small city of Northampton, but residences, while showing some clustering around Northampton, reach well into a rural hinterland. In these rural towns lesbians live at low physical densities while forming relatively high proportions of the towns’ populations. Unlike previous studies of gay male and lesbian space that have tended to focus on center cities, this paper starts to chart this space on the low‐density, semirural edge of a metropolitan area. Previous studies of residential concentrations of gay and lesbian persons have also found highly visible gay male territories ‐ sometimes with a lesbian minority ‐ but showed lesbians forming social networks or somewhat underground concentrations. Several parts of the Valley area are different; comprising a visibly lesbian space. This paper contributes to analyses of diverse populations in contemporary metropolitan and exurban regions and to discussions of methods in research on lesbian and gay populations.
Colonoscopic allergen provocation test with rBet v 1 in patients with pollen‐associated food allergy
Authors: Pickert C. N. , Lorentz A. , Manns M. P. , Bischoff S. C.
Published: August 2012

Background

After consumption of fruits, nuts, and vegetables, several patients with pollen allergy experience gastrointestinal (GI) tract symptoms that are possibly caused by pollen‐associated food allergy. The aim of this study was to evaluate the colonoscopic allergen provocation (COLAP) test using the recombinant birch pollen allergen Bet v 1 (rBet v 1) for in vivo diagnosis of pollen‐associated food allergy manifesting in the GI tract.

Methods

Thirty‐four patients with a history of adverse reactions to food, GI tract symptoms, and birch pollen pollinosis and five healthy controls underwent COLAP test. Twenty minutes after endoscopic challenge of the cecal mucosa with rBet v 1, the mucosal wheal and flare reaction was registered semiquantitatively, and tissue biopsy specimens were examined for eosinophil mucosal activation.

Results

The mucosal reaction to rBet v 1 was correlated with the presence of pollinosis (P = 0.004), history of adverse reaction to Bet v 1‐associated food allergens (P = 0.001), and tissue eosinophils' activation (P < 0.001). A wheal and flare reaction in the COLAP test was observed in 13 of 16 patients (81%) with a history of GI tract symptoms associated with the ingestion of Bet v 1‐related foods and in four of 18 (22%) patients with a negative history (P < 0.001). The control group did not develop visible mucosal reactions to rBet v 1. Systemic anaphylactic reactions did not occur.

Conclusions

The mucosal administration of rBet v 1 by COLAP test provides a new diagnostic tool that might support the diagnosis of Bet v 1‐associated food allergy manifesting in the GI tract.
Comparative study of one‐step nucleic acid amplification assay, frozen section, and touch imprint cytology for intraoperative assessment of breast sentinel lymph node in Chinese patients
Authors: Wang Yong‐sheng , Ou‐yang Tao , Wu Jiong , Liu Yan‐hui , Cao Xu‐chen , Sun Xiao , Fu Li , Liao Ning , Yang Wen‐tao , Zhong Wei‐xia , Lu Ai‐ping
Published: August 2012

Conventional procedures for the intraoperative assessment of breast cancer sentinel lymph nodes (SLNs) are frozen section (FS) and touch imprint cytology (TIC). The one‐step nucleic acid amplification (OSNA) assay is a novel molecular technique. The aim of this study was to evaluate the optimal approach by comparing OSNA assay, FS, and TIC. Five hundred and fifty‐two consecutive patients were enroled from five study centers in China. The SLNs were cut into alternating 2 mm blocks. The odd blocks were tested by the OSNA assay intraoperatively, and the even ones were assessed by postoperative histology (four 4‐ to 6‐μm‐thick sections were taken every 200 μm per block). In addition, intraoperative histological assessments were carried out on the even blocks of 211 patients by FS and all blocks of 552 patients by TIC. Overall performance of the assay compared to postoperative histology was: accuracy 91.4%; sensitivity 83.7%; and specificity 92.9%. The sensitivity of the assay was higher than FS (211 patients, 77.6% vs 69.7%; not significant, P = 0.286) and was significantly higher than TIC (552 patients, 83.6% vs 76.2%; P = 0.044). When assessing nodes with micrometastases, the sensitivity of the assay was higher than FS (17 nodes, 47.1% vs 23.5%; not significant, P = 0.289) and was significantly higher than TIC (48 nodes, 62.5% vs 35.4%; P = 0.007). The study indicated that the OSNA assay is an accurate and rapid intraoperative assay for assessing breast SLNs and it can replace FS and TIC for application in general medical practice. The trial was registered as: OSNA assay China Registration Study. Clinical trial registration number: China Breast Cancer Clinical Study Group 001c.
Discovery of Potent, Novel Nrf2 Inducers Via Quantum Modeling, Virtual Screening, and In Vitro Experimental Validation
Authors: Williamson Tracy P. , Amirahmadi Sara , Joshi Gururaj , Kaludov Nikola K. , Martinov Martin N. , Johnson Delinda A. , Johnson Jeffrey A.
Published: August 2012

Nuclear factor erythroid 2‐related factor 2 (Nrf2) is the master transcription factor of the antioxidant response element pathway, coordinating the induction of detoxifying and antioxidant enzymes. Nrf2 is normally sequestered in the cytoplasm by Kelch‐like ECH‐associating protein 1 (Keap1). To identify novel small molecules that will disturb Nrf2–Keap1 binding and promote activation of the Nrf2‐ antioxidant response element pathway, we generated a quantum model based on the structures of known Nrf2‐ antioxidant response element activators. We used the quantum model to perform in silico screening on over 18 million commercially available chemicals to identify the structures predicted to activate the Nrf2‐ antioxidant response element pathway based on the quantum model. The top hits were tested in vitro, and half of the predicted hits activated the Nrf2‐antioxidant response element pathway significantly in primary cell culture. In addition, we identified a new family of Nrf2‐antioxidant response element‐activating structures that all have comparable activity to tBHQ and protect against oxidative stress and dopaminergic toxins in vitro. The improved ability to identify potent activators of Nrf2 through the combination of in silico and in vitro screening described here improves the speed and cost associated with screening Nrf2‐antioxidant response element ‐activating compounds for drug development.
Association of 25‐hydroxyvitamin D with type 2 diabetes among patients undergoing coronary angiography: cross‐sectional findings from the LUdwigshafen Risk and Cardiovascular Health (LURIC) Study
Authors: O'Hartaigh Bríain , Neil Thomas G. , Silbernagel Günther , Bosch Jos A. , Pilz Stefan , Loerbroks Adrian , Kleber Marcus E. , Grammer Tanja B. , Böhm Bernhard O. , März Winfried
Published: August 2012

Objective

Evidence suggests that vitamin D may protect against the onset of diabetes. However, the mechanisms underlying the role of vitamin D on glycaemic status are unclear and warrant further investigation. We sought to determine the relationship between serum 25‐hydroxyvitamin D (25[OH]D) and glycaemic status among intermediate‐to‐high‐risk patients scheduled for coronary angiography.

Methods

Participants were 3316 male and female patients (mean ± SD age, 62·7 ± 10·6 years). Four categories were formed according to serum 25[OH]D levels. The association between serum 25[OH]D and diabetes was assessed using multivariable logistic regression.

Results

Fasting and 2 h post‐load glucose, HbA1c and the HOMA‐IR indices diminished with increasing serum 25[OH]D levels (P < 0·001). However, no associations were observed between insulin, pro‐insulin or C‐peptide and serum 25[OH]D concentrations. The pro‐inflammatory markers IL‐6 and hs‐CRP also decreased considerably with higher vitamin D levels (P < 0·001). After full adjustment, those with optimal serum 25[OH]D levels had a reduced odds for fasting diabetes (OR = 0·63; 95% CI, 0·46–0·86; Ptrend = 0·01), 2 h post‐load diabetes (OR = 0·46; 95% CI, 0·29–0·74; Ptrend = 0·004), both fasting/2 h post‐load diabetes (OR = 0·61; 95% CI, 0·42–0·87; Ptrend = 0·001) and all of the combined hyperglycaemic states (OR = 0·68; 95% CI, 0·52–0·80; Ptrend = 0·01).

Conclusions

Higher serum 25[OH]D levels were associated with better glycaemic status and lower inflammation. Should these observations be confirmed in future studies, vitamin D supplementation may prove a useful adjunct in attenuating the onset of diabetes.
The relation of vascular endothelial growth factor (VEGF) gene polymorphisms on VEGF levels and the risk of vasoocclusive crisis in sickle cell disease
Authors: Al‐Habboubi Hebah H. , Mahdi Najat , Abu‐Hijleh Tala M. , Abu‐Hijleh Farah M. , Sater Mai S. , Almawi Wassim Y.
Published: August 2012

Objective

The association of vascular endothelial growth factor (VEGFA) variants and VEGF secretion with sickle cell disease (SCD) vasoocclusive crisis (VOC) was investigated in 210 VOC patients and 114 pain‐free control patients.

Methods

VEGFA −2578C/A (rs699947), −460T/C (rs833061), −1154G/A (rs15703060), −634G/C (rs2010963), 398G/A (rs833068), 497G/A (rs833070), −583T/C (rs3025020), and 936C/T (rs3025039) were carried out by real‐time PCR.

Results

Higher frequency of rs2010963 C‐allele, rs833068 A‐allele, and rs3025020 C‐allele and significant differences in rs2010963, rs833068, and rs3025020 genotype distribution were seen in VOC than steady‐state patients. Increased VOC risk was seen with rs2010963 as heterozygous and more as homozygous, and in rs833068 and rs3025020 homozygous carriers. While there were no differences in VEGF levels between VOC and steady‐state controls, there was a progressive decline in serum VEGF in rs2010963 and rs833068 heterozygous and homozygous genotypes, but an opposite trend was seen in VOC patients. Haploview analysis revealed high LD between rs699947, rs833061, rs1570360, rs2010963, rs833068, and rs833070, but weak or no LD between rs3025020 and rs3025039 and other SNPs. Six‐locus (rs699947/rs833061/rs1570360/rs2010963/rs833068/rs833070) VEGFA haplotype analysis identified haplotype 111111 to be negatively (OR = 0.68) and haplotype 111222 to be positively (OR = 1.89) associated with VOC. rs2010963, rs833068, and rs3025020 were correlated with VOC type, while rs3025020 was correlated with hospitalization, VOC treatment, and duration.

Conclusion

Specific VEGFA variants contribute to the pathogenesis of SCD VOC.
Exposure to second‐hand smoke damages everyday prospective memory
Authors: Heffernan Thomas M. , O'Neill Terence S.
Published: August 2012

Aims

Prospective memory (PM: remembering future intentions and activities) is critical to everyday remembering. This study compared a group of never‐smokers who reported regular exposure to second‐hand smoke (the SHS group) with a group of current smokers (the CS group) and a group of never‐smokers who reported never having been exposed to SHS (the non‐SHS group) on objective PM.

Design

An existing groups design was employed to compare the SHS, CS and non‐SHS groups.

Participants and setting

Twenty‐four SHS, 27 CS and 28 non‐SHS were tested on objective PM. All participants were university undergraduates aged between 18–30 years. All participants were tested individually in a laboratory setting.

Measurements

The Cambridge Prospective Memory Test (CAMPROMPT) was used to assess objective PM. Age, other drug use, mood and IQ were also measured as covariates in the study.

Findings

The non‐SHS group recalled significantly more time‐based PM tasks than the SHS group (means = 16.3 versus 13.7, P < 0.001) and significantly more than the CS group (CS mean = 11.6, P < 0.001); and the SHS group recalled significantly more time‐based tasks than the CS group (P < 0.002). The non‐SHS group recalled significantly more event‐based PM tasks than the CS group (means = 15.2 versus 11.3, P < 0.002) with no significant difference between the non‐SHS group and SHS group (SHS mean = 14.3, P = 0.234); and the SHS group recalled significantly more event‐based tasks than the CS group (P < 0.001).

Conclusion

Non‐smokers exposed to second‐hand smoke may suffer impairment in time‐based prospective memory.
Maternal adversity and ecological stressors in natural populations: the role of stress axis programming in individuals, with implications for populations and communities
Authors: Love Oliver P. , McGowan Patrick O. , Sheriff Michael J.
Published: August 2012

Biomedical researchers have long appreciated that maternal stressors can induce preparative and adaptive programming in offspring via exposure to maternal Glucocorticoids (GCs). However, few ecologists are aware of the capacity for maternal GC exposure to translate ecological and environmental stressors into preparative and adaptive programmed offspring responses in free‐living systems. We review a growing body of experimental work indicating that circulating maternal GCs link ecological stressors with adaptive programming of the stress axis. Throughout, we emphasise that natural and human‐induced ecological stressors play a fundamental role in programming the capacity of individuals, populations and communities to respond to both predictable and unpredictable ecological change via translating maternal adversity into responsive programming of the vertebrate stress axis.

To encourage rigorous testing of this paradigm in a broad range of ecological systems, we introduce the principal extrinsic stressors with a recognised potential to alter maternal circulating GC levels. We then review from the biomedical literature regarding the underlying physiological and epigenetic mechanisms of stress‐induced programming of individual phenotypes to predict how variation in ecological stressors can produce individual variation in stress axis management.

To appreciate the potential evolutionary inertia (i.e. adaptive value) of maternally programmed individual variation, we review key recent studies in free‐living systems that test its adaptive function, and then discuss how variation in stress‐axis programming may scale up to influence populations and ecological communities.

Given the huge potential of this field, it is encouraging that ecologists are beginning to examine how and why maternal GCs translate ecological and environmental stressors into preparative stress axis programming in free‐living systems.
The effect of cooling on coagulation and haemostasis: Should “Ice” be part of treatment of acute haemarthrosis in haemophilia?
Authors: Forsyth A. L. , Zourikian N. , Valentino L. A. , Rivard G. E.
Published: August 2012

Repeated haemarthroses and the consequences of blood in the joint contribute to blood induced joint disease (BIJD) in people with haemophilia (PWH). Prevention of bleeding, through medical management, is the standard of care in developed countries, but is not universally available due to financial and other barriers. Ice application, as part of R.I.C.E. (Rest, Ice, Compression, Elevation) or alone, is commonly recommended as an adjunct treatment to decrease bleeding, pain, tissue metabolism, oedema, and inflammation. This article will review evidence regarding local cooling by commonly used ice application methods, to decrease the temperature of the skin and intra‐articular (IA) joint space and the resultant effects on haemostasis and coagulation. The general literature was reviewed for articles in English describing temperatures achievable in the skin and IA space using clinically relevant ice protocols, and the effect of cooling on haemostasis and coagulation. The literature demonstrates that typical methods of ice application can cool both the skin and IA space. Published, general literature studies have also consistently demonstrated that experimental cooling of blood and/or tissue, both in vitro and in vivo in humans and in animal models, can significantly impair coagulation and prolong bleeding. In PWH with acute haemarthrosis, ice application has potential to increase haemorrhage morbidity by further impairing coagulation and haemostasis. Ice has not been shown to improve overall outcome, stop bleeding nor swelling from haemarthrosis. Although ice can help manage acute, haemarthrosis‐related pain, there are other available interventions that will not impair coagulation and haemostasis.
PEGylated therapeutic proteins for haemophilia treatment: a review for haemophilia caregivers
Authors: Ivens I. A. , Baumann A. , McDonald T. A. , Humphries T. J. , Michaels L. A. , Mathew P.
Published: August 2012

PEGylation is the technology involving the covalent attachment of polyethylene glycol (PEG) to a protein‐, peptide‐ or small‐molecule drug to improve their pharmacokinetic, pharmacodynamic and immunological profiles, and thus, enhance the therapeutic effect. Today, PEGylation of proteins is a well‐established technology and is being used in the treatment of a variety of clinical disorders. Several PEGylated coagulation proteins for haemophilia A and B are under development with the goal of prolonging the circulation half‐life of factor VIII (FVIII) or factor IX. The prolongation of half‐life, resulting in less frequent injections can provide significant benefits in improving the quality of life of subjects with haemophilia and improvement in adherence to treatment. A review of published literature on PEGylated therapeutic products currently approved for human use and a discussion of a PEGylated recombinant FVIII molecule (BAY 94–9027, Bayer HealthCare, Berkeley, CA, USA) currently being investigated in the pivotal clinical trial prior to registration is provided. Available safety information of PEGylated proteins containing high molecular weight PEG does not indicate any safety concerns to date, following long‐term (chronic) use in animal models or patients. Chronic use of currently available PEGylated products has been shown to be safe, paving the way for chronic use of PEGylated coagulation products in persons with haemophilia.
Predicting dispersal distance in mammals: a trait‐based approach
Authors: Whitmee Sarah , Orme C. David L.
Published: August 2012

Dispersal is one of the principal mechanisms influencing ecological and evolutionary processes but quantitative empirical data are unfortunately scarce. As dispersal is likely to influence population responses to climate change, whether by adaptation or by migration, there is an urgent need to obtain estimates of dispersal distance.

Cross‐species correlative approaches identifying predictors of dispersal distance can provide much‐needed insights into this data‐scarce area. Here, we describe the compilation of a new data set of natal dispersal distances and use it to test life‐history predictors of dispersal distance in mammals and examine the strength of the phylogenetic signal in dispersal distance.

We find that both maximum and median dispersal distances have strong phylogenetic signals. No single model performs best in describing either maximum or median dispersal distances when phylogeny is taken into account but many models show high explanatory power, suggesting that dispersal distance per generation can be estimated for mammals with comparatively little data availability.

Home range area, geographic range size and body mass are identified as the most important terms across models. Cross‐validation of models supports the ability of these variables to predict dispersal distances, suggesting that models may be extended to species where dispersal distance is unknown.
Investigating face‐to‐face peer interaction patterns in a collaborative Web discovery task: the benefits of a shared display
Authors: Chung C‐W. , Lee C‐C. , Liu C‐C.
Published: August 2012

Mobile computers are now increasingly applied to facilitate face‐to‐face collaborative learning. However, the factors affecting face‐to‐face peer interactions are complex as they involve rich communication media. In particular, non‐verbal interactions are necessary to convey critical communication messages in face‐to‐face communication. Through gathering discourse and non‐verbal interaction records, this study explores the peer interactions supported by two collaborative applications: one with mobile computers and the other with shared‐display groupware (SDG). The results show that the students tended to interact with each other according to a distributed and an unsocial interaction pattern when using the application with mobile computers. In contrast, the students who learned with the SDG demonstrated a shared interaction pattern, whereby they often jointly focused on and referred to the shared work. The analysis of the students' work further found that a higher level of discussion was generally associated with the shared interaction pattern. The results seem to support SDG as being useful in augmenting face‐to‐face peer interaction supported by mobile computers. The implications derived from the findings also support the argument that non‐verbal interaction records are useful for quantitatively and qualitatively analysing face‐to‐face peer interactions.
Low numbers of repeat units in variable number of tandem repeats (VNTR) regions of white spot syndrome virus are correlated with disease outbreaks
Authors: Hoa T T T , Zwart M P , Phuong N T , de Jong M C M , Vlak J M
Published: August 2012

White spot syndrome virus (WSSV) is the most important pathogen in shrimp farming systems worldwide including the Mekong Delta, Vietnam. The genome of WSSV is characterized by the presence of two major ‘indel regions’ found at ORF14/15 and ORF23/24 (WSSV‐Thailand) and three regions with variable number tandem repeats (VNTR) located in ORF75, ORF94 and ORF125. In the current study, we investigated whether or not the number of repeat units in the VNTRs correlates with virus outbreak status and/or shrimp farming practice. We analysed 662 WSSV samples from individual WSSV‐infected Penaeus monodon shrimp from 104 ponds collected from two important shrimp farming regions of the Mekong Delta: Ca Mau and Bac Lieu. Using this large data set and statistical analysis, we found that for ORF94 and ORF125, the mean number of repeat units (RUs) in VNTRs was significantly lower in disease outbreak ponds than in non‐outbreak ponds. Although a higher mean RU number was observed in the improved‐extensive system than in the rice‐shrimp or semi‐intensive systems, these differences were not significant. VNTR sequences are thus not only useful markers for studying WSSV genotypes and populations, but specific VNTR variants also correlate with disease outbreaks in shrimp farming systems.
Characterization of myocardial lesions associated with cardiomyopathy syndrome in Atlantic salmon, Salmo salar L., using laser capture microdissection
Authors: Wiik‐Nielsen J , Løvoll M , Fritsvold C , Kristoffersen A B , Haugland Ø , Hordvik I , Aamelfot M , Jirillo E , Koppang E O , Grove S
Published: August 2012

Cardiomyopathy syndrome (CMS) in Atlantic salmon, Salmo salar L., is characterized by focal infiltration in the spongy myocardium and endocardium of the heart. The origin of the mononuclear infiltrate is unknown. Using experimentally infected fish, we investigated localization of the causative agent, piscine myocarditis virus (PMCV), within the heart and characterized the cell population associated with myocardial lesions. Cellular and transcriptional characteristics in the lesions were compared with adjacent non‐infiltrated tissues using laser capture microdissection, RT‐qPCR and immunohistochemistry. Our results reveal that PMCV is almost exclusively present in myocardial lesions. The inflammatory infiltrate comprises a variety of leucocyte populations, including T cells, B cells, MHC class II+ and CD83+ cells, most likely of the macrophage line. Correlation analyses demonstrated co‐ordinated leucocyte activity at the site of the virus infection. Cellular proliferation and/or DNA repair was demonstrated within the myocardial lesions. Different cell populations, mainly myocytes, stained positive for proliferating cell nuclear antigen (PCNA). Densities of endothelial cells and fibroblasts were not significantly increased. The simultaneous presence of PMCV and various inflammatory cells in all myocardial lesions analysed may indicate that both viral lytic and immunopathological effects may contribute to the pathogenesis of CMS.
Three‐dimensional nanofabrication of polystyrene by focused ion beam
Authors: LEE C.C. , PROUST G. , ALICI G. , SPINKS G.M. , CAIRNEY J.M.
Published: August 2012

Focused ion beam micromachining provides a maskless and resistless technique for prototyping of structures from thermoplastic polymers, an example being the production of polystyrene microcantilevers with potential applications as micro/nanoelectromechanical systems sensors and actuators. The applicability of FIB technology is, however, often restricted by the damage created by high energy gallium ion bombardment and local beam heating, which can affect the desired properties and limit the minimum achievable size of the fabricated structure. To investigate the ion‐induced damage and determine the limitations of the technique for polymer nanofabrication, we have exposed thin polystyrene film to the ion beam at varying ion doses, ion energies and specimen temperatures. Ion doses ranging from 1016 to 1018 ions cm−2 show significant gallium implantation, redeposition of sputtered material and chemical degradation in the polymer. Raman results show that the local heating in polymer during milling is severe at room temperature, damaging the aromatic carbon bonding (C = C) in particular. These observations are supported by the results of a beam heating model and Monte Carlo simulations. The chemical degradation caused by local beam heating is found to be significantly reduced by cooling the specimen to −25°C during milling. This is consistent with observations that reversible and repeatable thermal actuation of a fabricated polystyrene–platinum microcantilever is only observed when the cantilever is prepared at low temperature milling. Using this cooling approach, polymer structures can be fabricated with dimensions as low as 200 nm and still retain a sufficient volume of material unaffected by the ion beam.
Induction of slow oscillations by rhythmic acoustic stimulation
Authors: NGO HONG‐VIET V. , CLAUSSEN JENS C. , BORN JAN , MÖLLE MATTHIAS
Published: August 2012

Slow oscillations are electrical potential oscillations with a spectral peak frequency of ∼0.8 Hz, and hallmark the electroencephalogram during slow‐wave sleep. Recent studies have indicated a causal contribution of slow oscillations to the consolidation of memories during slow‐wave sleep, raising the question to what extent such oscillations can be induced by external stimulation. Here, we examined whether slow oscillations can be effectively induced by rhythmic acoustic stimulation. Human subjects were examined in three conditions: (i) with tones presented at a rate of 0.8 Hz (‘0.8‐Hz stimulation’); (ii) with tones presented at a random sequence (‘random stimulation’); and (iii) with no tones presented in a control condition (‘sham’). Stimulation started during wakefulness before sleep and continued for the first ∼90 min of sleep. Compared with the other two conditions, 0.8‐Hz stimulation significantly delayed sleep onset. However, once sleep was established, 0.8‐Hz stimulation significantly increased and entrained endogenous slow oscillation activity. Sleep after the 90‐min period of stimulation did not differ between the conditions. Our data show that rhythmic acoustic stimulation can be used to effectively enhance slow oscillation activity. However, the effect depends on the brain state, requiring the presence of stable non‐rapid eye movement sleep.
Insect P450s: mounted for battle in their war against toxins
Authors: SCHULER MARY A.
Published: August 2012

Transcriptome profiling methods are rapidly changing the ways in which insect responses to the environment can be assessed. One article featured in this issue of Molecular Ecology utilizes global expression analysis to extend previous studies examining the basis of insecticide resistance in Helicoverpa species that are devastating crop pests worldwide. In this issue Tao et al. (2012) have used a wide spectrum of biochemical and molecular techniques to examine the extent to which naturally occurring plant compounds and one synthetic insecticide change transcriptome profiles of Helicoverpa armigera larvae (Fig. 1) to enhance their adaptation to plant toxins and insecticides in their diet and environment. With their data highlighting an array of P450 transcripts and a few esterase transcripts that are correlated with increased tolerance to the insecticide deltamethrin, these researchers provide the first comprehensive evaluation of cytochrome P450 monooxygenase (P450), glutathione S‐transferase (GST) and esterase (Est) gene responses in a lepidopteran species repeatedly subjected to pyrethroid selection. Building on this information, these researchers venture into the realm of the biorational in showing that RNAi‐mediated destruction of one prominent toxin‐inducible P450 transcript can increase sensitivity to deltamethrin, thereby compromising larval growth in the presence of this insecticide. The fact that the resulting levels of deltamethrin tolerance in the RNAi‐silenced larvae are not restored completely to the levels in larvae whose defences are not stimulated by consuming plant compounds provides further evidence that their adaptive strategies for survival in toxin‐rich environments include many different P450, esterase and, possibly, other genes. Together, their data highlight the complexity of the defence systems evolving in lepidopterans and other insect pests.

 Helicoverpa armigera on cotton flower bud.

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Association of TNF‐α polymorphisms with adult dermatomyositis and systemic lupus erythematosus in Bulgarian patients
Authors: Dourmishev Lyubomir , Kamenarska Zornitsa , Hristova Maria , Dodova Rumyana , Kaneva Radka , Mitev Vanio
Published: August 2012

Background Single‐nucleotide polymorphisms (SNPs) of tumor necrosis factor‐alpha (TNF‐α) have been implicated in various autoimmune diseases; however, the results are quite controversial, and there is still no widely accepted opinion about their role in the pathology of the autoimmune diseases. This is a pilot study to investigate the association of six SNPs of the TNF‐α gene with the risk of adult dermatomyositis (DM) and systemic lupus erythematosus (SLE) in Bulgarian patients.

Materials and methods Twenty‐seven patients with DM and 27 with SLE were included in this study. Genomic DNA was extracted from the peripheral blood, and six SNPs (−1031T/C, −863C/A, −857C/T, −308G/A, −238G/A, +489G/A) were selected for investigation by polymerase chain reaction‐restriction fragment length polymorphism analysis.

Results We found association between the TNF‐α−1031CC genotype and SLE (P = 0.025) and tendency for association with DM (P = 0.0876). The association appeared even stronger in the female patients with SLE (P = 0.024) and DM (P = 0.067). The TNF‐α−857GG genotype shows weak association with SLE (P = 0.097, OR 2.06, 95% CI 0.81–5.29) when analyzed for the whole group, but it appeared significantly associated with SLE in women (P = 0.048, OR 3.23, 95% CI 0.93–11.14). The −863C allele showed association with arthritis in patients with SLE (P = 0.008). The haplotype analysis revealed a significant association between TNF −1031C/−863C/−857C/−308G/+489G haplotype with both DM (P = 0.022) and SLE (P = 0.007) in women.

Conclusions The TNF‐α polymorphisms are associated with increased relative risk mainly for SLE, particularly in women, while their role for DM is less evident and needs further analysis in an enlarged sample cohort.