bluuebunny/crossref_metadata_2025 huggingface dataset:
Organising non‐standard workers: union recruitment in the Irish care sector
Authors: Murphy Caroline , Turner Thomas
Published: August 2014

In 2004, Ireland's largest union initiated its most comprehensive organising campaign to date, resulting in 12,000 care workers being organised. This article explores how unions can sustain campaigns among a dispersed workforce, and how public support and worker commitment can be leveraged to achieve structural changes in an emerging sector.
The reform of Joint Labour Committees—the re‐commodification of labour?
Authors: Whitston Colin
Published: August 2014

The reform of Joint Labour Committees in Ireland is analysed as a victory for neoliberalism within the shell of pluralist traditions in industrial relations: a floor of rights is transformed into an ‘iron ceiling’; worker voice is drastically reduced; reform is consistent with the re‐commodification of labour within the EU.
Cephalostachyum chevalieri a new synonym of Kinabaluchloa wrayi (Poaceae: Bambusoideae), and a new bamboo record for Vietnam
Authors: Tran Van Tien , Xia Nian‐He , Nguyen Hoang Nghia , Diep My Hanh
Published: August 2014

Cephalostachyum chevalieri A. Camus is found to be a new synonym of Kinabaluchloa wrayi (Stapf) K. M. Wong, extending the species range from the Malay Peninsula to Vietnam. Its type, Chevalier 4485, and other specimens collected from the type locality, have the same culm leaf, pseudo‐spikelet and flower characteristics as K. wrayi.
Evaluation of a Regional Approach to Standards for Plug‐in Battery Electric Vehicles in Future Light‐Duty Vehicle Greenhouse Gas Regulations
Authors: MacPherson Nathan D. , Keoleian Gregory A. , Kelly Jarod C.
Published: August 2014

Representing the greenhouse gas (GHG) emissions attributable to plug‐in electric vehicles (PEV) in vehicle GHG emissions regulations is complex because of spatial and temporal variation in fueling sources and vehicle use. Previous work has shown that the environmental performance of PEVs significantly varies depending on the characteristics of the electricity grid and how the vehicle is driven. This article evaluates the U.S. Environmental Protection Agency's (EPA's) GHG emissions accounting methodology in current and future standards for new electrified vehicles. The current approach employed by the EPA in their 2017–2025 model year light‐duty vehicle GHG regulation is compared with an accounting mechanism where the actual regional sales of PEVs, and the regional electricity emission factor in the year sold, are used to determine vehicle compliance value. Changes to the electricity grid over time and regional vehicle sales are included in the modeling efforts. A projection of a future GHG regulation past the 2017–2025 rule is used to observe the effect of such a regional regulation. The results showed that the complexity involved in tracking and accounting for regional PEV sales will not dramatically increase the effectiveness of the regulations to capture PEV electricity‐related GHG emissions in the absence of a major policy shift. A discussion of the feasibility and effectiveness of a regional standard for PEVs, and notable examples of region‐specific regulations instated in past energy policies, is also addressed.
Calcium contributes to photoprotection and repair of photosystem II in peanut leaves during heat and high irradiance
Authors: Yang Sha , Wang Fang , Guo Feng , Meng Jing‐Jing , Li Xin‐Guo , Wan Shu‐Bo
Published: August 2014

In this study, we investigated the effects of exogenous calcium nitrate on photoinhibition and thylakoid protein level in peanut plants under heat (40 °C) and high irradiance (HI) (1,200 µmol/m2 per s) stress. Compared with control seedlings (cultivated in 0 mmol/L Ca(NO3)2 medium), the maximal photochemical efficiency of photosystem II (PSII) in Ca2+‐treated plants showed a slight decrease after 5 h stress, accompanied by lower degree of PSII closure (1‐qP), higher non‐photochemical quenching, and lower level of membrane damage. Ca2+ inhibitors were used to analyze the varieties of antioxidant enzymes activity and PSII proteins. These results indicated that Ca2+ could protect the subunits of PSII reaction centers from photoinhibition by reducing the generation of reactive oxygen species. In the presence of both ethyleneglycol‐bis(2‐aminoethylether)‐tetraacetic acid and ascorbic acid (AsA), the net degradation of the damaged D1 protein was faster than that only treated with AsA. Our previous study showed that either the transcriptional or the translational level of calmodulin was obviously higher in Ca2+‐treated plants. These results suggested that, under heat and HI stress, the Ca2+ signal transduction pathway can alleviate the photoinhibition through regulating the protein repair process besides an enhanced capacity for scavenging reactive oxygen species.
Deficit of astroglia‐derived thrombospondin‐1 and loss of synaptic proteins in hepatic encephalopathy: do ammonia‐overexposed astrocytes derange the synaptic hardware?
Authors: Albrecht Jan , Zielińska Magdalena
Published: August 2014

Read the full article ‘Decreased astrocytic thrombospondin‐1 secretion after chronic ammonia treatment reduces the level of synaptic proteins: in vitro and in vivo studies’ on page 333
Hepatic fungal infection in a young beagle with unrecognised hereditary cobalamin deficiency (Imerslund‐Gräsbeck syndrome)
Authors: Kook P. H. , Drögemüller M. , Leeb T. , Hinden S. , Ruetten M. , Howard J.
Published: August 2014

A 12‐month‐old beagle presented for anorexia, pyrexia and vomiting. The dog had been treated intermittently with antibiotics and corticosteroids for inappetence and lethargy since five months of age. Previous laboratory abnormalities included macrocytosis and neutropenia. At presentation, the dog was lethargic, febrile and thin. Laboratory examination findings included anaemia, a left shift, thrombocytopenia, hypoglycaemia and hyperbilirubinaemia. Multiple, small, hypoechoic, round hepatic lesions were observed on abdominal ultrasound. Cytological examination of hepatic fine needle aspirates revealed a fungal infection and associated pyogranulomatous inflammation. The dog's general condition deteriorated despite supportive measures and treatment with fluconazole, and owners opted for euthanasia before hypocobalaminaemia was identified. Subsequent genomic analysis revealed aCUBN:c.786delCmutation in a homozygous state, confirming hereditary cobalamin malabsorption (Imerslund‐Gräsbeck syndrome). Similar to human infants, dogs with Imerslund‐Gräsbeck syndrome may rarely be presented for infectious diseases, distracting focus from the underlying primary disorder.
Retrospective clinical evaluation of hypobaric spinal anaesthesia in dogs undergoing pelvic limb orthopaedic surgery
Authors: De Gennaro C. , Vettorato E. , Corletto F.
Published: August 2014

OBJECTIVE

To evaluate intraoperative effects, complications, postoperative rescue analgesia requirement and presence of postoperative unilateral blockade after hypobaric spinal anaesthesia in dogs.

METHODS

Retrospective review of case records of dogs that underwent pelvic limb orthopaedic surgery and received hypobaric spinal anaesthesia. Cases that contained complete information on perioperative analgesia, end tidal anaesthetic agent, arterial blood pressure, postoperative urination, motor function and assessment at the sixth week re‐examination were selected.

RESULTS

Twenty‐four of forty‐eight records were sufficiently complete to meet the selection criteria. Local anaesthetic dose and volume of the solution administered were 0 · 22 (±0 · 06) mg/kg and 0 · 16 (±0 · 05) mL/kg, respectively. Fentanyl was administered intraoperatively in seven dogs (29%); mean ± sd end‐expired isoflurane was 1 · 09 ± 0 · 17%; hypotension was observed in nine dogs (37 · 5%). Unilateral blockade was documented in 18 dogs (75%); 6 dogs (25%) required methadone postoperatively; urinary retention was not observed. One dog developed steroid responsive meningitis arteritis.

CLINICAL SIGNIFICANCE

Hypobaric spinal anaesthesia achieved unilateral postoperative pelvic limb motor blockade in dogs, although bilateral block occurred in a proportion of animals; intraoperative hypotension was not infrequent. Fentanyl and postoperative methadone might be required to control nociception and pain, despite technical success in performing spinal anaesthesia.
Serum microRNA‐124 is a novel biomarker for liver necroinflammation in patients with chronic hepatitis B virus infection
Authors: Wang J.‐Y , Mao R.‐C , Zhang Y.‐M , Zhang Y.‐J , Liu H.‐Y , Qin Y.‐L , Lu M.‐J , Zhang J.‐M
Published: August 2014

Patients with chronic hepatitis B virus (HBV) infection and normal or mildly increased transaminases may have sustained significant liver damage, as verified by liver biopsy. However, no suitable noninvasive method exists for identifying liver necroinflammation in such patients. We aimed to investigate the power of microRNA‐124 as a novel biomarker for liver necroinflammation. A total of 131 recruited patients with chronic HBV infection underwent liver biopsy for grading of necroinflammation (G) and staging of fibrosis (S). Thirty healthy individuals were included as controls (HCs). Serum microRNA‐124 and microRNA‐122 levels were measured using qRT‐PCR. Forty‐five patients from the study population receiving entecavir therapy were monitored for changes in serum microRNA‐124 levels in association with improved liver histology. The capacity of serum microRNA‐124 levels in discriminating the grade of liver necroinflammation was compared with alanine aminotransferase (ALT) with liver biopsy validation. Serum microRNA‐124 levels were significantly higher in patients with chronic HBV infection than in HCs (P < 0.0001). Patients with considerable liver necroinflammation (G ≥ 2) had significantly higher serum miRNA‐124 levels than those without or with mild necroinflammation (P < 0.0001). After 48 weeks of antiviral therapy, serum microRNA‐124 levels considerably declined in 45 patients (P < 0.0001), which were associated with histological improvement. In patients with normal ALT and a serum HBV DNA load >104 copies/mL, receiver operating characteristic (ROC) curve of serum microRNA‐124 levels yielded an area under ROC curve (AUC) of 0.840, with 58.3% sensitivity and 91.7% specificity in discriminating between moderate‐to‐severe liver necroinflammation (G ≥ 2).
HBV preS2 transactivates FOXP3 expression in malignant hepatocytes
Authors: Zhang Xiaoning , Gao Lifen , Liang Xiaohong , Guo Min , Wang Rong , Pan Yingfang , Liu Peng , Zhang Feng , Guo Chun , Zhu Faliang , Qu Chunfeng , Ma Chunhong
Published: August 2014

Background & Aims

Recent data reported the increased expression of forkhead box protein 3 (FOXP3), the well known master regulator of CD4+C25+ regulatory T cells, in hepatocellular carcinoma (HCC) cells. However, the mechanisms remain unknown. We previously showed that preS2, one of important regulatory proteins encoded by HBV, triggers transactivation of hTERT in malignant hepatocytes. Here, we aimed to explore the role of preS2 in regulating FOXP3 expression in HCC.

Methods

FOXP3 expression was detected by RT‐PCR, Western blot and immunohistochemical staining. Cotransfection and siRNA knockdown were involved to study the regulation effects of preS2 on FOXP3 expression in cultured HCC cell lines. Luciferase reporter assay and EMSA assay were performed to explore the mechanism of preS2‐mediated FOXP3 upregulation.

Results

Immunohistochemical staining detected significant increased FOXP3 expression in malignant hepatocytes from sections of HCC patients. The total FOXP3 expression in hepatocytes from patients with HBsAg‐positive HCC was significantly increased compared to that of HBV‐negative HCCs (P = 0.002). In accordance, preS2 overexpression enhanced FOXP3 expression in HCC cell lines, while preS2 knockdown significantly reduced FOXP3 expression in HBV‐integrated HepG2.2.15 cells. Results of cotransfection and luciferase report assay showed that preS2 transactivated FOXP3 promoter in a dose‐dependent manner. Further study identified the AP‐1 binding site at 20 bp region from −465 bp to −445 bp of FOXP3 promoter was responsible for preS2‐induced FOXP3 transcriptional activation.

Conclusions

Our data here, for the first time, provided direct evidence to demonstrate that preS2 oncoprotein encoded by HBV transactivated FOXP3 transcription in HCC cells.
CINCINNATA in Antirrhinum majus directly modulates genes involved in cytokinin and auxin signaling
Authors: Das Gupta Mainak , Aggarwal Pooja , Nath Utpal
Published: August 2014

Mutations in the CINCINNATA (CIN) gene in Antirrhinum majus and its orthologs in Arabidopsis result in crinkly leaves as a result of excess growth towards the leaf margin. CIN homologs code for TCP (TEOSINTE‐BRANCHED 1, CYCLOIDEA, PROLIFERATING CELL FACTOR 1 AND 2) transcription factors and are expressed in a broad zone in a growing leaf distal to the proliferation zone where they accelerate cell maturation. Although a few TCP targets are known, the functional basis of CIN‐mediated leaf morphogenesis remains unclear.

We compared the global transcription profiles of wild‐type and the cin mutant of A. majus to identify the targets of CIN. We cloned and studied the direct targets using RNA in situ hybridization, DNA–protein interaction, chromatin immunoprecipitation and reporter gene analysis.

Many of the genes involved in the auxin and cytokinin signaling pathways showed altered expression in the cin mutant. Further, we showed that CIN binds to genomic regions and directly promotes the transcription of a cytokinin receptor homolog HISTIDINE KINASE 4 (AmHK4) and an IAA3/SHY2 (INDOLE‐3‐ACETIC ACID INDUCIBLE 3/SHORT HYPOCOTYL 2) homolog in A. majus.

Our results suggest that CIN limits excess cell proliferation and maintains the flatness of the leaf surface by directly modulating the hormone pathways involved in patterning cell proliferation and differentiation during leaf growth.
Cartesian Modes and The Simplicity of Mind
Authors: Barry Galen
Published: August 2014

Malebranche argues that we lack a clear idea of the mind because we cannot, even in principle, derive all the possible modes of mind solely from the idea of thought. But we can, in principle, derive all the possible modes of body from the idea of extension. Therefore, there is epistemic asymmetry between our ideas of mind and body. I offer a defense ofDescartes whereby he can assert that we have a clear idea of mind despite this asymmetry. I argue that he can do this by distinguishing the simplicity of mind from the divisibility of body.
Skin as a living coloring book: how epithelial cells create patterns of pigmentation
Authors: Weiner Lorin , Fu Wenyu , Chirico William J. , Brissette Janice L.
Published: August 2014

The pigmentation of mammalian skin and hair develops through the interaction of two basic cell types — pigment donors and recipients. The pigment donors are melanocytes, which produce and distribute melanin through specialized structures. The pigment recipients are epithelial cells, which acquire melanin and put it to use, collectively yielding the pigmentation visible to the eye. This review will focus on the pigment recipients, the historically less understood cell type. These end‐users of pigment are now known to exert a specialized control over the patterning of pigmentation, as they identify themselves as melanocyte targets, recruit pigment donors, and stimulate the transfer of melanin. As such, this review will discuss the evidence that the skin is like a coloring book: the pigment recipients create a ‘picture,’ a blueprint for pigmentation, which is colorless initially but outlines where pigment should be placed. Melanocytes then melanize the recipients and ‘color in’ the picture.
Directed Improvement of Luciferin Regenerating Enzyme Binding Properties: Implication of Some Conserved Residues in Luciferin‐Binding Domain
Authors: Hemmati Roohullah , Sajedi Reza H. , Bakhtiari Nuredin , Hosseinkhani Saman
Published: August 2014

Luciferin regenerating enzyme (LRE) contributes to in vitro recycling of d‐luciferin to produce persistent and longer light emission by luciferase. Luciferin binding domains I and II among LREs regarded as potential candidates for luciferin‐binding sites. In this study, for the first time, amino acids T69, G75 and K77 located at luciferin binding domain I of LRE from L. turkestanicus (T‐LRE) substituted by using site‐directed mutagenesis. Single mutant T69R increased luciferase light output more than two‐fold over a longer time in comparison with a wild‐type and other mutants of T‐LRE. Nevertheless, double mutant (K77E/T69R) increased the amount of bioluminescent signal more than two‐fold over a short time. In addition, G75E, K77E and G75E/T69R mutants did not improve luciferin–luciferase in vitro bioluminescence. Based on our results, addition of K77E/G75E and K77E/G75E/T69R mutants caused intermediate changes in bioluminescence from in vitro luciferin–luciferase reaction. These findings indicated that the amino acids in question are possible to be located within T‐LRE active site. It may also be suggested that substituted Arg69 (Arg218) plays an important role in luciferin binding and the existence of Gly75 as well as Lys77 is essential for T‐LRE which has already evolved to have different functions in nature.
Forward Simulation Markov Chain Monte Carlo with Applications to Stochastic Epidemic Models
Authors: Neal Peter , Terry Huang Chien Lin
Published: August 2014

For many stochastic models, it is difficult to make inference about the model parameters because it is impossible to write down a tractable likelihood given the observed data. A common solution is data augmentation in a Markov chain Monte Carlo (MCMC) framework. However, there are statistical problems where this approach has proved infeasible but where simulation from the model is straightforward leading to the popularity of the approximate Bayesian computation algorithm. We introduce a forward simulation MCMC (fsMCMC) algorithm, which is primarily based upon simulation from the model. The fsMCMC algorithm formulates the simulation of the process explicitly as a data augmentation problem. By exploiting non‐centred parameterizations, an efficient MCMC updating schema for the parameters and augmented data is introduced, whilst maintaining straightforward simulation from the model. The fsMCMC algorithm is successfully applied to two distinct epidemic models including a birth–death–mutation model that has only previously been analysed using approximate Bayesian computation methods.
Estimating Mean Survival Time: When is it Possible?
Authors: Ding Ying , Nan Bin
Published: August 2014

For right‐censored survival data, it is well‐known that the mean survival time can be consistently estimated when the support of the censoring time contains the support of the survival time. In practice, however, this condition can be easily violated because the follow‐up of a study is usually within a finite window. In this article, we show that the mean survival time is still estimable from a linear model when the support of some covariate(s) with non‐zero coefficient(s) is unbounded regardless of the length of follow‐up. This implies that the mean survival time can be well estimated when the support of linear predictor is wide in practice. The theoretical finding is further verified for finite samples by simulation studies. Simulations also show that, when both models are correctly specified, the linear model yields reasonable mean square prediction errors and outperforms the Cox model, particularly with heavy censoring and short follow‐up time.
Scarcity of protective items against HIV and other bloodborne infections in 13 low‐ and middle‐income countries
Authors: Gupta Shailvi , Wong Evan G. , Kushner Adam L.
Published: August 2014

Objective

To assess protection of surgical healthcare workers against HIV and other bloodborne infections in low‐ and middle‐income countries (LMICs).

Methods

Literature review based on recent studies assessing baseline surgical capacity in LMICs using the WHO Situational Analysis of Access to Emergency and Essential Surgical Care, the Surgeons OverSeas (SOS) Personnel, Infrastructure, Procedures, Equipment and Supplies (PIPES) survey and the Harvard Humanitarian Initiative survey tools. The availability of protective eyewear, sterile gloves and sterilisers was assessed.

Results

Thirteen individual country studies with relevant data were identified documenting items from 399 hospitals. The countries included Afghanistan, Bolivia, Gambia, Ghana, Liberia, Mongolia, Nigeria, Sierra Leone, Solomon Islands, Somalia, Sri Lanka, Tanzania and Zambia. Overall, only 29% (79/270) of hospitals always had eye protection. Sterilisers were only available at 64% (244/383) of facilities. Sterile gloves were the most available item, available at 75% of facilities (256/340).

Conclusion

Surgical healthcare worker protection for bloodborne infections continues to be deficient in LMICs. Improved documentation of these items should be incorporated into future surgical capacity studies. Policy makers and clinicians should work together to secure resources and interventions that will protect this vital workforce.
The phylogenetic relationships of the Early Miocene storkGrallavis edwardsi, with comments on the interrelationships of living Ciconiidae (Aves)
Authors: De Pietri Vanesa L. , Mayr Gerald
Published: August 2014

The fossil record of storks (Aves, Ciconiidae) includes a relatively large number of specimens from the Middle Eocene onwards, but no taxon is as well represented asGrallavis edwardsiform the Early Miocene of the Allier region in central France. Despite this, the phylogenetic placement ofG. edwardsiamong other storks has remained elusive not least because of the lack of a robust phylogenetic framework for living storks. To find out howG. edwardsirelates to recent Ciconiidae, we performed a phylogenetic analysis based on osteological features including all living genus‐level taxa of the Ciconiidae. We show that the previously reported similarities to the extant taxaEphippiorhynchusandJabiruare based on plesiomorphic features, and our analysis supports a sister group relationship betweenGrallavis edwardsiandLeptoptilos. Our results are also consistent with a basal divergence within Ciconiidae betweenMycteriaandAnastomus, which are among the smallest storks, and all other storks. A sister group relationship between storks of the genusCiconiaand all large storks (Leptoptilini) is recovered albeit with weak support, which may be due to homoplastic features linked to their large size.Grallavis edwardsipossessed several osteological adaptations suited for scavenging, and despite lacking some derived traits characteristic ofLeptoptilos, it is likely to have been a precursor of large marabou and adjutant storks.
Measurement of time delays in gated radiotherapy for realistic respiratory motions
Authors: Chugh Brige P. , Quirk Sarah , Conroy Leigh , Smith Wendy L.
Published: August 2014

Purpose:

Gated radiotherapy is used to reduce internal motion margins, escalate target dose, and limit normal tissue dose; however, its temporal accuracy is limited. Beam‐on and beam‐off time delays can lead to treatment inefficiencies and/or geographic misses; therefore, AAPM Task Group 142 recommends verifying the temporal accuracy of gating systems. Many groups use sinusoidal phantom motion for this, under the tacit assumption that use of sinusoidal motion for determining time delays produces negligible error. The authors test this assumption by measuring gating time delays for several realistic motion shapes with increasing degrees of irregularity.

Methods:

Time delays were measured on a linear accelerator with a real‐time position management system (Varian TrueBeam with RPM system version 1.7.5) for seven motion shapes: regular sinusoidal; regular realistic‐shape; large (40%) and small (10%) variations in amplitude; large (40%) variations in period; small (10%) variations in both amplitude and period; and baseline drift (30%). Film streaks of radiation exposure were generated for each motion shape using a programmable motion phantom. Beam‐on and beam‐off time delays were determined from the difference between the expected and observed streak length.

Results:

For the system investigated, all sine, regular realistic‐shape, and slightly irregular amplitude variation motions had beam‐off and beam‐on time delays within the AAPM recommended limit of less than 100 ms. In phase‐based gating, even small variations in period resulted in some time delays greater than 100 ms. Considerable time delays over 1 s were observed with highly irregular motion.

Conclusions:

Sinusoidal motion shapes can be considered a reasonable approximation to the more complex and slightly irregular shapes of realistic motion. When using phase‐based gating with predictive filters even small variations in period can result in time delays over 100 ms. Clinical use of these systems for patients with highly irregular patterns of motion is not advised due to large beam‐on and beam‐off time delays.
Crystal structure of the CRISPR RNA–guided surveillance complex from
Escherichia coli
Authors: Jackson Ryan N. , Golden Sarah M. , van Erp Paul B. G. , Carter Joshua , Westra Edze R. , Brouns Stan J. J. , van der Oost John , Terwilliger Thomas C. , Read Randy J. , Wiedenheft Blake
Published: August 2014

A foreign-DNA–destroying machine

Bacteria have an adaptive immune system, called CRISPR, that identifies invading viruses through their DNA or RNA sequences and cuts them up (see the Perspective by Zhang and Sontheimer). Jackson
et al.
and Mulepati
et al.
have determined the structure of the large protein complex, called Cascade, that targets the invading nucleic acids and does the cutting. The seahorse-shaped structure reveals how the 11 subcomponents of Cascade assemble into the final protein complex. The structure also shows how Cascade presents the short CRISPR-derived RNAs so that they can bind and target foreign DNA.

Science
, this issue p.
1473
and p.
1479
; see also p.
1452
Structure of an agonist-bound ionotropic glutamate receptor
Authors: Yelshanskaya Maria V. , Li Minfen , Sobolevsky Alexander I.
Published: August 2014

Activating a receptor to excite a neuron

Transmitting signals between nerve cells, occuring at structures known as synapses, is critical to processes such as learning and memory. Fast transmission occurs when glutamate is released from a presynaptic neuron and binds to ionotropic glutamate receptors (iGluRs) in the cell membrane of a postsynaptic neuron. The iGluR contains an ion channel that is transiently opened, to activate the postsynaptic neuron, but then closes rapidly. Chen
et al.
and Yelshanskaya
et al.
report crystal structures in a range of conformations that together provide insight into how glutamate binding causes the channel to open and how other molecules that bind to the receptor modulate this. The information could aid in the design of drugs to treat cognitive impairment or seizure disorders

Science
, this issue p.
1021
and p.
1070
C9orf72
repeat expansions cause neurodegeneration in
Drosophila
through arginine-rich proteins
Authors: Mizielinska Sarah , Grönke Sebastian , Niccoli Teresa , Ridler Charlotte E. , Clayton Emma L. , Devoy Anny , Moens Thomas , Norona Frances E. , Woollacott Ione O. C. , Pietrzyk Julian , Cleverley Karen , Nicoll Andrew J. , Pickering-Brown Stuart , Dols Jacqueline , Cabecinha Melissa , Hendrich Oliver , Fratta Pietro , Fisher Elizabeth M. C. , Partridge Linda , Isaacs Adrian M.
Published: August 2014

Dipeptide repeat peptides on the attack

Certain neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), are associated with expanded dipeptides translated from RNA transcripts of disease-associated genes (see the Perspective by West and Gitler). Kwon
et al.
show that the peptides encoded by the expanded repeats in the C9orf72 gene interfere with the way cells make RNA and kill cells. These effects may account for how this genetic form of ALS causes disease. Working in
Drosophila
, Mizielinska
et al.
aimed to distinguish between the effects of repeat-containing RNAs and the dipeptide repeat peptides that they encode. The findings provide evidence that dipeptide repeat proteins can cause toxicity directly.

Science
, this issue p.
1139
and p.
1192
; see also p.
1118
X-ray structures of AMPA receptor–cone snail toxin complexes illuminate activation mechanism
Authors: Chen Lei , Dürr Katharina L. , Gouaux Eric
Published: August 2014

Activating a receptor to excite a neuron

Transmitting signals between nerve cells, occuring at structures known as synapses, is critical to processes such as learning and memory. Fast transmission occurs when glutamate is released from a presynaptic neuron and binds to ionotropic glutamate receptors (iGluRs) in the cell membrane of a postsynaptic neuron. The iGluR contains an ion channel that is transiently opened, to activate the postsynaptic neuron, but then closes rapidly. Chen
et al.
and Yelshanskaya
et al.
report crystal structures in a range of conformations that together provide insight into how glutamate binding causes the channel to open and how other molecules that bind to the receptor modulate this. The information could aid in the design of drugs to treat cognitive impairment or seizure disorders

Science
, this issue p.
1021
and p.
1070
Genome Sequences of 228 Shiga Toxin-Producing Escherichia coli Isolates and 12 Isolates Representing Other Diarrheagenic E. coli Pathotypes
Authors: Trees Eija , Strockbine Nancy , Changayil Shankar , Ranganathan Satishkumar , Zhao Kun , Weil Ryan , MacCannell Duncan , Sabol Ashley , Schmidtke Amber , Martin Haley , Stripling Devon , Ribot Efrain M. , Gerner-Smidt Peter
Published: August 2014

Shiga toxin-producing
Escherichia coli
(STEC) are a common cause for food-borne diarrheal illness outbreaks and sporadic cases. Here, we report the availability of the draft genome sequences of 228 STEC strains representing 32 serotypes with known pulsed-field gel electrophoresis (PFGE) types and epidemiological relationships, as well as 12 strains representing other diarrheagenic
E. coli
pathotypes.
Draft Genome Sequence of the Dye-Decolorizing and Nanowire-Producing Bacterium Shewanella xiamenensis BC01
Authors: Li Yuzhe , Ng I-Son , Zhang Xia , Wang Nan
Published: August 2014

Shewanella xiamenensis
BC01 is an important biodecolorizing and nanowire-producing bacterium which was found in Xiamen, China. Here, we present the draft genome sequence consisting of 4,677,169 bp (GC content, 46.21%) and 3,999 coded proteins. This information boosts insight into and understanding of the genetic evolution of
Shewanella
species.
Draft Genome Sequence of the Rodent Opportunistic Pathogen Pasteurella pneumotropica ATCC 35149
T
Authors: Sasaki Hiraku , Ishikawa Hiroki , Asano Ryoki , Ueshiba Hidehiro , Matsumoto Tetsuya , Boot Ron , Kawamoto Eiichi
Published: August 2014

Pasteurella pneumotropica
is an opportunistic pathogen in rodents that is commonly isolated from upper respiratory tracts in laboratory rodents. Here, we report the draft genome sequence of the
P. pneumotropica
type strain ATCC 35149, which was first isolated and characterized as biotype Jawetz.
Draft Genome Sequence of a Hypersensitive Reaction-Inducing Pantoea agglomerans Strain Isolated from Olive Knots Caused by Pseudomonas savastanoi pv. savastanoi
Authors: Moretti Chiaraluce , Cortese Chiara , Passos da Silva Daniel , Venturi Vittorio , Torelli Emanuela , Firrao Giuseppe , Buonaurio Roberto
Published: August 2014

Pantoea agglomerans
strains inducing a hypersensitive reaction in tobacco leaves are frequently isolated inside olive knots caused by
Pseudomonas savastanoi
pv. savastanoi. Here, we report the draft genome sequence of the Italian
P. agglomerans
strain, which is able to increase olive knot disease severity when coinoculated with
P. savastanoi
pv. savastanoi.
Draft Genome Sequences of Clinical Vibrio parahaemolyticus Strains Isolated in Maryland (2010 to 2013)
Authors: Haendiges Julie , Timme Ruth , Allard Marc , Myers Robert A. , Payne Justin , Brown Eric W. , Evans Peter , Gonzalez-Escalona Narjol
Published: August 2014

Vibrio parahaemolyticus
is the leading cause of food-borne illnesses associated with the consumption of raw shellfish worldwide. Here, we report 45 draft genomes of
V. parahaemolyticus
. Thirty-five of them are strains that were isolated from clinical cases in the state of Maryland from 2010 to 2013. The remaining 10 strains were historical isolates, isolated mostly from the West Coast of the United States during the period of 1988 to 2004. The availability of these genomes will allow for future phylogenetic analyses with other
V. parahaemolyticus
strains.
P AUTOMATA WITH RESTRICTED POWER
Authors: CSUHAJ-VARJÚ ERZSÉBET , VASZIL GYÖRGY
Published: August 2014

P automata are variants of symport/antiport membrane systems which describe string languages by applying a mapping to the sequence of multisets entering the system during computations. In this paper, we study their computational power in the case when the input mapping associates each input multiset with the set of strings consisting of all permutations of its elements. We show that P automata of this type are strictly less powerful than so-called restricted logarithmic space Turing machines, and we also exhibit a strict infinite hierarchy within the accepted language class based on the number of membranes present in the system.
HYPERGRAPH AUTOMATA: A THEORETICAL MODEL FOR PATTERNED SELF-ASSEMBLY
Authors: KARI LILA , KOPECKI STEFFEN , SIMJOUR AMIRHOSSEIN
Published: August 2014

Patterned self-assembly is a process whereby coloured tiles self-assemble to build a rectangular coloured pattern. We propose self-assembly (SA) hypergraph automata as an automata-theoretic model for patterned self-assembly. We investigate the computational power of SA-hypergraph automata and show that for every recognizable picture language, there exists an SA-hypergraph automaton that accepts this language. Conversely, we prove that for any restricted SA-hypergraph automaton, there exists a Wang Tile System, a model for recognizable picture languages, that accepts the same language. The advantage of SA-hypergraph automata over Wang automata, acceptors for the class of recognizable picture languages, is that they do not rely on an a priori defined scanning strategy.
APPLICATIONS OF FINSLER GEOMETRY TO SPEED LIMITS TO QUANTUM INFORMATION PROCESSING
Authors: RUSSELL BENJAMIN , STEPNEY SUSAN
Published: August 2014

We are interested in fundamental limits to computation imposed by physical constraints. In particular, the physical laws of motion constrain the speed at which a computer can transition between well-defined states. Here, we discuss speed limits in the context of quantum computing. We review some relevant parts of the theory of Finsler metrics on Lie groups and homogeneous spaces such as the special unitary groups and complex projective spaces. We show how these constructions can be applied to analysing the limit to the speed of quantum information processing operations in constrained quantum systems with finite dimensional Hilbert spaces of states. We demonstrate the approach applied to a spin chain system.
Three-nucleon forces
Authors: Sauer Peter U.
Published: August 2014

In this paper, the role of three-nucleon forces in ab initio calculations of nuclear systems is investigated. The difference between genuine and induced many-nucleon forces is emphasized. Induced forces arise in the process of solving the nuclear many-body problem as technical intermediaries toward calculationally converged results. Genuine forces make up the Hamiltonian. They represent the chosen underlying dynamics. The hierarchy of contributions arising from genuine two-, three- and many-nucleon forces is discussed. Signals for the need of the inclusion of genuine three-nucleon forces are studied in nuclear systems, technically best under control, especially in three-nucleon and four-nucleon systems. Genuine three-nucleon forces are important for details in the description of some observables. Their contributions to observables are small on the scale set by two-nucleon forces.
新西兰的中国跨国移民
Authors: 刘良妮
Published: August 2014

基于47份在不同国家（中国大陆、新西兰、澳大利亚）展开的对中国移民的深入访谈，本文专注于探讨中国移民初始移民新西兰的原因、定居该国后回归中国或移民到第三国现象，以及长期频繁往返于原居地和移民国的深层动机。本文还着重讨论家庭问题在跨国移民决策中的考量、移民对未来定居地的选择和跨国移民倾向，以及对国籍、身份认同和对“家”这个研究移民的重要概念的理解。探讨途径以移民家庭为考察单位，将每场独立面谈置于受访者的家庭背景和实际情况中分析。研究结果表明，中国移民的跨国移民机动性十分灵活，许多中国移民在移民新西兰后还具有强烈的再移民倾向。他们跨国移民的原因和动机是多重的。这些原因可以是宏观的，联系到社会的体制与经济的前景，也可以是个体或家庭层面的原因。本研究也发现对不同家庭成员需要的考量，在中国移民跨国移民的轨迹中占有重要的主导性。移民的孩子和年老的父母是影响移民家庭做出跨国移民决定的两项重要考虑。中国移民的多国跨越性决定了他们对“家”、国籍、身份认同等相关概念认知的多样性。
Leukocyte Telomere Length in Relation to Pancreatic Cancer Risk: A Prospective Study
Authors: Campa Daniele , Mergarten Björn , De Vivo Immaculata , Boutron-Ruault Marie-Christine , Racine Antoine , Severi Gianluca , Nieters Alexandra , Katzke Verena A. , Trichopoulou Antonia , Yiannakouris Nikos , Trichopoulos Dimitrios , Boeing Heiner , Quirós J. Ramón , Duell Eric J. , Molina-Montes Esther , Huerta José María , Ardanaz Eva , Dorronsoro Miren , Khaw Kay-Tee , Wareham Nicholas , Travis Ruth C. , Palli Domenico , Pala Valeria , Tumino Rosario , Naccarati Alessio , Panico Salvatore , Vineis Paolo , Riboli Elio , Siddiq Afshan , Bueno-de-Mesquita H.B. , Peeters Petra H. , Nilsson Peter M. , Sund Malin , Ye Weimin , Lund Eiliv , Jareid Mie , Weiderpass Elisabete , Duarte-Salles Talita , Kong So Yeon , Stepien Magdalena , Canzian Federico , Kaaks Rudolf
Published: August 2014

Background: Several studies have examined leukocyte telomere length (LTL) as a possible predictor for cancer at various organ sites. The hypothesis originally motivating many of these studies was that shorter telomeres would be associated with an increase in cancer risk; the results of epidemiologic studies have been inconsistent, however, and suggested positive, negative, or null associations. Two studies have addressed the association of LTL in relation to pancreatic cancer risk and the results are contrasting.

Methods: We measured LTL in a prospective study of 331 pancreatic cancer cases and 331 controls in the context of the European Prospective Investigation into Cancer and Nutrition (EPIC).

Results: We observed that the mean LTL was higher in cases (0.59 ± 0.20) than in controls (0.57 ± 0.17), although this difference was not statistically significant (P = 0.07), and a basic logistic regression model showed no association of LTL with pancreas cancer risk. When adjusting for levels of HbA1c and C-peptide, however, there was a weakly positive association between longer LTL and pancreatic cancer risk [OR, 1.13; 95% confidence interval (CI), 1.01–1.27]. Additional analyses by cubic spline regression suggested a possible nonlinear relationship between LTL and pancreatic cancer risk (P = 0.022), with a statistically nonsignificant increase in risk at very low LTL, as well as a significant increase at high LTL.

Conclusion: Taken together, the results from our study do not support LTL as a uniform and strong predictor of pancreatic cancer.

Impact: The results of this article can provide insights into telomere dynamics and highlight the complex relationship between LTL and pancreatic cancer risk. Cancer Epidemiol Biomarkers Prev; 23(11); 2447–54. ©2014 AACR.
Polymorphisms in MicroRNAs Are Associated with Survival in Non–Small Cell Lung Cancer
Authors: Zhao Yang , Wei Qingyi , Hu Lingming , Chen Feng , Hu Zhibin , Heist Rebecca S. , Su Li , Amos Christopher I. , Shen Hongbing , Christiani David C.
Published: August 2014

Background: MicroRNAs (miRNA) play important roles in the regulation of eukaryotic gene expression and are involved in human carcinogenesis. Single-nucleotide polymorphisms (SNP) in miRNA sequence may alter miRNA functions in gene regulation, which, in turn, may affect cancer risk and disease progression.

Methods: We conducted an analysis of associations of 142 miRNA SNPs with non–small cell lung cancer (NSCLC) survival using data from a genome-wide association study (GWAS) in a Caucasian population from the Massachusetts General Hospital (Boston, MA) including 452 early-stage and 526 late-stage NSCLC cases. Replication analyses were further performed in two external populations, one Caucasian cohort from The University of Texas MD Anderson Cancer Center (Houston, TX) and one Han Chinese cohort from Nanjing, China.

Results: We identified seven significant SNPs in the discovery set. Results from the independent Caucasian cohort demonstrated that the C allele of rs2042253 (hsa-miRNA-5197) was significantly associated with decreased risk for death among the patients with late-stage NSCLC (discovery set: HR, 0.80; P = 0.007; validation set: HR, 0.86; P = 0.035; combined analysis: HR, 0.87; P = 0.007).

Conclusions: These findings provide evidence that some miRNA SNPs are associated with NSCLC survival and can be used as predictive biomarkers.

Impact: This study provided an estimate of outcome probability for survival experience of patients with NSCLC, which demonstrates that genetic factors, as well as classic nongenetic factors, may be used to predict individual outcome. Cancer Epidemiol Biomarkers Prev; 23(11); 2503–11. ©2014 AACR.
Regulation of OSU-03012 Toxicity by ER Stress Proteins and ER Stress–Inducing Drugs
Authors: Booth Laurence , Roberts Jane L. , Cruickshanks Nichola , Grant Steven , Poklepovic Andrew , Dent Paul
Published: August 2014

The present studies examined the toxic interaction between the non-coxib celecoxib derivative OSU-03012 and phosphodiesterase 5 (PDE5) inhibitors, and also determined the roles of endoplasmic reticulum stress response regulators in cell survival. PDE5 inhibitors interacted in a greater than additive fashion with OSU-03012 to kill parental glioma and stem-like glioma cells. Knockdown of the endoplasmic reticulum stress response proteins IRE1 or XBP1 enhanced the lethality of OSU-03012, and of [OSU-03012 + PDE5 inhibitor] treatment. Pan-caspase and caspase-9 inhibition did not alter OSU-03012 lethality but did abolish enhanced killing in the absence of IRE1 or XBP1. Expression of the mitochondrial protective protein BCL-XL or the caspase-8 inhibitor c-FLIP-s, or knockdown of death receptor CD95 or the death receptor caspase-8 linker protein FADD, suppressed killing by [OSU-03012 + PDE5 inhibitor] treatment. CD95 activation was blocked by the nitric oxide synthase inhibitor L-NAME. Knockdown of the autophagy regulatory proteins Beclin1 or ATG5 protected the cells from OSU-03012 and from [OSU-03012 + PDE5 inhibitor] toxicity. Knockdown of IRE1 enhanced OSU-03012/[OSU-03012 + PDE5 inhibitor]–induced JNK activation, and inhibition of JNK suppressed the elevated killing caused by IRE1 knockdown. Knockdown of CD95 blunted JNK activation. Collectively, our data demonstrate that PDE5 inhibitors recruit death receptor signaling to enhance OSU-03012 toxicity in glioblastoma multiforme (GBM) cells. Mol Cancer Ther; 13(10); 2384–98. ©2014 AACR.
Medical Genetic Counseling for Breast Cancer in Primary Care: A Synthesis of Major Determinants of Physicians' Practices in Primary Care Settings
Authors: Jbilou Jalila , Halilem Norrin , Blouin-Bougie Jolyane , Amara Nabil , Landry Réjean , Simard Jacques
Published: August 2014

Objectives: This paper aims to identify relevant potential predictors of medical genetic counseling for breast cancer (MGC-BC) in primary care and to develop a comprehensive questionnaire to study MGC-BC. Methods: A scoping review was conducted to identify the predictors of MGC-BC among primary care physicians. Relevant articles were identified in selected databases (PubMed, Embase, CINAHL, ISI Web of Science, PsycINFO, and Cochrane CENTRAL) and 4 selected relevant electronic journals. Results: An inductive analysis of the 193 quantitatively tested variables, conducted by 3 researchers, showed that 6 conceptual categories of determinants, namely (1) demographic, (2) organizational, (3) experiential, (4) professional, (5) psychological, and (6) cognitive, influence MGC-BC practices. Conclusion: There is a scarcity of literature addressing the medical behavior determinants of MGC-BC. Future research is needed to identify effective strategies put into action to support the integration of MGC-BC in primary care medical practices and routines. However, our results shed light on 2 levels of actions that could improve genetic counseling services in primary care: (1) medical training and educational efforts emphasizing family history collection (individual level), and (2) clarification of roles and responsibilities in ordering and referral practices in genetic counseling and genetic testing for better healthcare management (organizational level).
Hyperbaric Oxygen Therapy in Acute Ischemic Stroke: A Review
Authors: Ding Zheng , Tong Wesley C. , Lu Xiao-Xin , Peng Hui-Ping
Published: August 2014

Stroke, also known as cerebrovascular disease, is a common and serious neurological disease, which is also the fourth leading cause of death in the United States so far. Hyperbaric medicine, as an emerging interdisciplinary subject, has been applied in the treatment of cerebral vascular diseases since the 1960s. Now it is widely used to treat a variety of clinical disorders, especially hypoxia-induced disorders. However, owing to the complex mechanisms of hyperbaric oxygen (HBO) treatment, the therapeutic time window and the undefined dose as well as some common clinical side effects (such as middle ear barotrauma), the widespread promotion and application of HBO was hindered, slowing down the hyperbaric medicine development. In August 2013, the US Food and Drug Administration declared artery occlusion as one of the 13 specific indications for HBO therapy. This provides opportunities, to some extent, for the further development of hyperbaric medicine. Currently, the mechanisms of HBO therapy for ischemic stroke are still not very clear. This review focuses on the potential mechanisms of HBO therapy in acute ischemic stroke as well as the time window.
Tissue factor, protease activated receptors and pathologic heart remodelling
Authors: Antoniak Silvio , Sparkenbaugh Erica , Pawlinski Rafal
Published: August 2014

Tissue factor is the primary initiator of coagulation cascade and plays an essential role in haemostasis and thrombosis. In addition, tissue factor and coagulation proteases contribute to many cellular responses via activation of protease activated receptors. The heart is an organ with high levels of constitutive tissue factor expression. This review focuses on the role of tissue factor, coagulation proteases and protease activated receptors in heart haemostasis and the pathological heart remodelling associated with myocardial infarction, viral myocarditis and hypertension.