bluuebunny/crossref_metadata_2025 huggingface dataset:
Type 2 Diabetes Mellitus and the Risk of Hepatitis C Virus Infection: A systematic review
Authors: Guo Xuan , Jin Min , Yang Ming , Liu Ke , Li Jun-wen
Published: October 2013

The aim of this study was to evaluate the relationship between type 2 diabetes mellitus (T2DM) and hepatitis C virus (HCV) infection and to examine whether T2DM enhances the risk of HCV infection compared with the risk in the general population. We followed standard guidelines to perform a meta-analysis. The associated literature was selected based on the established inclusion criteria. The summary odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association. Through electronic database and manual searching, 22 studies were identified for the final analysis, which included a total of 78,051 individuals. Based on the random effects model, the meta-analysis results showed that patients with T2DM were at a higher risk of acquiring HCV infection than non-T2DM patients (summary OR = 3.50, 95% CI = 2.54–4.82, I2 = 82.3%). Based on the current limited evidence, this study suggests that T2DM is associated with increased susceptibility to HCV infection.
Chemical tools to probe cellular O-GlcNAc signalling
Authors: Ostrowski Adam , van Aalten Daan M. F.
Published: October 2013

Protein O-GlcNAcylation is an abundant, dynamic and reversible type of protein post-translational modification in animals that has been implicated in signalling processes linked to innate immunity, stress response, growth factor response, transcription, translation and proteosomal degradation. Only two enzymes, O-GlcNAc (O-linked N-acetylglucosamine) transferase and O-GlcNAcase, catalyse the reversible addition of the O-GlcNAc residue to over 1000 target proteins in the human cell. Recent advances in our understanding of the structures and mechanisms of these enzymes have resulted in the development of potent and selective inhibitors. The present review gives an overview of these inhibitors and how they have been used on cell lines, primary cells and animals to modulate O-GlcNAc levels and study the effects on signal transduction.
Travel to School and Housing Markets: A Case Study of Sheffield, England
Authors: Ferrari Ed , Green Mark A
Published: October 2013

How children travel to school is at the centre of a complex set of interrelated issues with significant policy implications. This paper reviews the relation of patterns of travel to school to concerns about public health, school choice, urban form, and residential housing markets. The spatial relations between pupils' homes and the schools that they attend provides the basis of an analytical framework that links local neighbourhood characteristics, school performance, and house prices to the distance and mode of travel to school and the level of ‘excess commuting’ in the urban system. A unique analysis of several integrated micro-datasets from Sheffield, UK, suggests that, while there are high levels of excess commuting, there remains a complex interrelationship between housing and neighbourhood characteristics, school performance, and commuting patterns. There are differences between the pictures for primary schools and secondary schools. Policies aimed at promoting transport efficiency and those promoting school choice are likely to remain in tension.
Smart Cities and Green Growth: Outsourcing Democratic and Environmental Resilience to the Global Technology Sector
Authors: Viitanen Jenni , Kingston Richard
Published: October 2013

Climate change and advances in urban technology propel forward the ‘smart city’. As decision makers strive to find a technological fix, smart city strategies are often based on technological orthodoxies which are conceptually and empirically shallow. The motivation behind this paper is to address the conceptual adolescence which relates to the wholesale digitisation of the city by pursuing a twin argument about the democratic and environmental consequences. The authors draw on interdisciplinary theory and insights from urban studies, infrastructure, informatics, and the sociology of the Internet to critique the way the ‘smart city’ is taken forward. It is concluded that private firms market smart city services and solutions based on an ideological legacy of ‘ubiquitous computing’, ‘universal infrastructure’, and ‘green technology’. Based on evidence from three UK cities—Manchester, Birmingham, and Glasgow—it is argued that the underlying principle of future city strategies is to expand the market for new technology products and services to support ‘green growth’ with disregard for their wider impacts. For citizens, becoming a consumer of the technologies is often presented as progressive ‘participation’ or ‘empowerment’ with unknown or hidden consequences both political and environmental. The city systems become a digital marketplace where citizen-consumers' participation is increasingly involuntary and the hegemony of global technology firms is inflated. What follows is that the city's ‘intelligent systems' are defined through a digital consumer experience that has inherent biases and leaves parts of the city and its population unaccounted for. This renders the city less resilient in the face of future social and climatic risks.
Heat-stress-induced reproductive failures in chickpea (Cicer arietinum) are associated with impaired sucrose metabolism in leaves and anthers
Authors: Kaushal Neeru , Awasthi Rashmi , Gupta Kriti , Gaur Pooran , Siddique Kadambot H. M. , Nayyar Harsh
Published: October 2013

Chickpea (Cicer arietinum L.), in its reproductive stage, is sensitive to heat stress (32/20°C or higher as day/night temperatures) with consequent substantial loss of potential yields at high temperatures. The physiological mechanisms associated with reproductive failures have not been established: they constitute the basis of this study. Here, we initially screened a large core-collection of chickpea against heat stress and identified two heat-tolerant (ICC15614, ICCV. 92944) and two heat-sensitive (ICC10685, ICC5912) genotypes. These four genotypes were sown during the normal time of sowing (November–March) and also late (February–April) to expose them to heat stress during reproductive stage (>32/20°C). The genotypes were assessed for damage by heat stress to the leaves and reproductive organs using various indicators of stress injury and reproductive function. In the heat-stressed plants, phenology accelerated as days to flowering and podding, and biomass decreased significantly. The significant reduction in pod set (%) was associated with reduced pollen viability, pollen load, pollen germination (in vivo and in vitro) and stigma receptivity in all four genotypes. Heat stress inhibited pollen function more in the sensitive genotypes than in the tolerant ones, and consequently showed significantly less pod set. Heat stress significantly reduced stomatal conductance, leaf water content, chlorophyll, membrane integrity and photochemical efficiency with a larger effect on heat-sensitive genotypes. Rubisco (carbon-fixing enzyme) along with sucrose phosphate synthase (SPS) and sucrose synthase (SS) (sucrose-synthesising enzymes) decreased significantly in leaves due to heat stress leading to reduced sucrose content. Invertase, a sucrose-cleaving enzyme, was also inhibited along with SPS and SS. The inhibition of these enzymes was significantly greater in the heat-sensitive genotypes. Concurrently, the anthers of these genotypes had significantly less SPS and SS activity and thus, sucrose content. As a result, pollen had considerably lower sucrose levels, resulting in reduced pollen function, impaired fertilisation and poor pod set in heat-sensitive genotypes.
The pattern of LH secretion and the ovarian response to the ‘ram effect’ in the anoestrous ewe is influenced by body condition but not by short-term nutritional supplementation
Authors: Scaramuzzi R. J. , Oujagir L. , Menassol J-B. , Freret S. , Piezel A. , Brown H. M. , Cognié J. , Fabre Nys C.
Published: October 2013

In sheep, the ‘ram effect’ induces out-of-season fertility and good nutrition increases prolificacy. This experiment determined if fatness or short-term nutritional supplementation modified the response to the ‘ram effect’. A group of 48 Île-de-France ewes were fed diets that produced groups with body-condition scores (BCS) of >3.0 and <2.0. Within each BCS group animals were supplemented daily with 500 g of lupins from Day –5 to Day 0 (ram introduction) resulting in four groups: low BCS, supplemented (n = 7) and non-supplemented (n = 8) and high BCS, supplemented (n = 12) and non-supplemented (n = 11). The blood concentrations of glucose and insulin and the LH response to gonadotrophin-releasing hormone (GnRH) were determined. After the ‘ram effect’ the pattern of LH pulsatility, the LH surge and ovarian responses were analysed. Low BCS ewes had lower glucose and insulin (P < 0.001) and supplementation increased both (P ≤ 0.001). The increase in LH induced by GnRH was reduced in low BCS ewes (P = 0.015) but it was not affected by supplementation. Similarly, LH pulsatility was reduced in low BCS ewes (P < 0.05). The LH surge and ovarian cyclicity were not affected but the follow-up cycle was delayed (P = 0.034) and progesterone was reduced (P = 0.029) in low BCS ewes. There was an effect of BCS on ovulation rate (P < 0.05). These results show that the BCS can modify the response to the ‘ram effect’ and that supplementation has little effect on this response.
MicroRNA-based regulation of epithelial–hybrid–mesenchymal fate determination
Authors: Lu Mingyang , Jolly Mohit Kumar , Levine Herbert , Onuchic José N. , Ben-Jacob Eshel
Published: October 2013

Significance

Epithelial–mesenchymal transitions play crucial roles in embryonic development, wound healing, and cancer metastasis. It is clearly of interest to quantitatively understand the core circuitry that takes input from the cell’s environment to perform this cell-fate decision. We devised a unique model of the microRNA (miR)-based coupled chimeric modules underlying this core circuit; this effort utilizes a unique theoretical framework for treating miR dynamics. We show that the miR-200/ZEB module functions as a ternary switch, allowing not only for the epithelial and mesenchymal phenotypes but also for a hybrid phenotype with mixed characteristics of collective cell migration, as seen in branching morphogenesis and wound closure. Our results provide valuable clues on how to control and reverse epithelial–hybrid–mesenchymal transitions.
Enhanced Threat Detection in Experienced Riot Police Officers: Cognitive Evidence from the Face-in-the-Crowd Effect
Authors: Damjanovic Ljubica , Pinkham Amy E. , Clarke Philip , Phillips Jeremy
Published: October 2013

We explored how varying levels of professional expertise in hostile crowd management could enhance threat detection capabilities as assessed by the face in the crowd paradigm. Trainee police officers and more experienced police officers specialized in, and having extensive experience with, riot control, were compared with participants with no experience in hostile crowd management on their search times and accuracy levels in detecting angry and happy face targets against a display of emotional and neutral distractor faces. The experienced officers relative to their trainee counterparts and nonpolice controls showed enhanced detection for threatening faces in both types of display along with a greater degree of inhibitory control over angry face distractors. These findings help to reinforce the ecological validity of the face in the crowd paradigm and provide a new theoretical link for the role of individual differences on the attentional processing of socially relevant stimuli.
Carbapenem De-escalation Therapy in a Resource-Limited Setting
Authors: Apisarnthanarak Anucha , Bhooanusas Nuntanij , Yaprasert Apiwat , Mundy Linda M.
Published: October 2013

Pulmonary infection (P = .01) and an infectious diseases consultation (P = .04) were associated with carbapenem de-escalation; pulmonary infection and septic shock were associated with unsuccessful de-escalation. Successful de-escalaltion was associated with lower mortality (0% vs 23%; P < .001) and shorter duration of carbapenem use (4 vs 10 days; P ≤.001).
Management of Neurosurgical Instruments and Patients Exposed to Creutzfeldt-Jakob Disease
Authors: Belay Ermias D. , Blase Jennifer , Sehulster Lynne M. , Maddox Ryan A. , Schonberger Lawrence B.
Published: October 2013

Objective.

To summarize the approaches used to manage exposure of patients to inadequately sterilized neurosurgical instruments contaminated as a result of Creutzfeldt-Jakob disease (CJD).

Methods.

Information on past CJD exposure incidents reported to the Centers for Disease Control and Prevention (CDC) was aggregated and summarized. In addition, inactivation studies were reviewed, and data from selected publications were provided for reference.

Results.

Nineteen incidents of patient exposure to potentially CJD-contaminated instruments were reported to the CDC, including 17 that involved intracranial procedures and 2 that involved ophthalmologic procedures. In more than 50% of incidents, the neurosurgical procedures were performed for diagnostic work up of the index patients. At least 12 of the hospitals had multiple neurosurgical sets, and the CJD-contaminated instruments could not be identified in 11 of 19 hospitals. In 12 of 15 hospitals with neurosurgical incidents, a decision was made to notify patients of their potential exposure.

Conclusions.

Neurosurgical instruments used for treatment of patients with suspected or diagnosed CJD or patients whose diagnosis is unclear should be promptly identified and sterilized using recommended CJD decontamination protocols. Inability to trace instruments complicates appropriate management of exposure incidents. The feasibility of instituting instrument tracking procedures should be considered.
Stathmin and microtubules regulate mitotic entry in HeLa cells by controlling activation of both Aurora kinase A and Plk1
Authors: Silva Victoria C. , Cassimeris Lynne
Published: October 2013

Depletion of stathmin, a microtubule (MT) destabilizer, delays mitotic entry by ∼4 h in HeLa cells. Stathmin depletion reduced the activity of CDC25 and its upstream activators, Aurora A and Plk1. Chemical inhibition of both Aurora A and Plk1 was sufficient to delay mitotic entry by 4 h, while inhibiting either kinase alone did not cause a delay. Aurora A and Plk1 are likely regulated downstream of stathmin, because the combination of stathmin knockdown and inhibition of Aurora A and Plk1 was not additive and again delayed mitotic entry by 4 h. Aurora A localization to the centrosome required MTs, while stathmin depletion spread its localization beyond that of γ-tubulin, indicating an MT-dependent regulation of Aurora A activation. Plk1 was inhibited by excess stathmin, detected in in vitro assays and cells overexpressing stathmin–cyan fluorescent protein. Recruitment of Plk1 to the centrosome was delayed in stathmin-depleted cells, independent of MTs. It has been shown that depolymerizing MTs with nocodazole abrogates the stathmin-depletion induced cell cycle delay; in this study, depolymerization with nocodazole restored Plk1 activity to near normal levels, demonstrating that MTs also contribute to Plk1 activation. These data demonstrate that stathmin regulates mitotic entry, partially via MTs, to control localization and activation of both Aurora A and Plk1.
CCN2 modulates hair follicle cycling in mice
Authors: Liu Shangxi , Leask Andrew
Published: October 2013

It is critical to understand how stem cell activity is regulated during regeneration. Hair follicles constitute an important model for organ regeneration because, throughout adult life, they undergo cyclical regeneration. Hair follicle stem cells—epithelial cells located in the follicle bulge—are activated by periodic β-catenin activity, which is regulated not only by epithelial-derived Wnt, but also, through as-yet-undefined mechanisms, the surrounding dermal microenvironment. The matricellular protein connective tissue growth factor (CCN2) is secreted into the microenvironment and acts as a multifunctional signaling modifier. In adult skin, CCN2 is largely absent but is unexpectedly restricted to the dermal papillae and outer root sheath. Deletion of CCN2 in dermal papillae and the outer root sheath results in a shortened telogen-phase length and elevated number of hair follicles. Recombinant CCN2 causes decreased β-catenin stability in keratinocytes. In vivo, loss of CCN2 results in elevated numbers of K15-positive epidermal stem cells that possess elevated β-catenin levels and β-catenin–dependent reporter gene expression. These results indicate that CCN2 expression by dermal papillae cells is a physiologically relevant suppressor of hair follicle formation by destabilization of β-catenin and suggest that CCN2 normally acts to maintain stem cell quiescence.
How Has U.S. Farm Policy Influenced Fruit and Vegetable Production?
Authors: Balagtas Joseph V. , Krissoff Barry , Lei Lei , Rickard Bradley J.
Published: October 2013

Eligibility requirements for farm payments include restrictions from planting certain horticultural crops on base acres, and U.S. commitments under the WTO have brought pressure to remove such restrictions. Using a difference‐in‐difference estimator, we measure the effects of the planting restriction on acres planted to horticultural and program crops using U.S. county‐level data from both the 1987 and 1997 U.S. Census of Agriculture, that is, both before and after the initial policy was introduced in 1990. We find that the planting restriction has crowded out fruit and vegetable acreage nationally, and most notably in selected Sunbelt states, a region that specializes in horticultural crop production. The key policy implication is that the removal of the planting restriction may have a nontrivial impact on U.S. fruit and vegetable production.
Membrane-Targeted HrpNEaCan Modulate Apple Defense Gene Expression
Authors: Vergne E. , de Bernonville T. Dugé , Dupuis F. , Sourice S. , Cournol R. , Berthelot P. , Barny M. A. , Brisset M. N. , Chevreau E.
Published: October 2013

Fire blight caused by Erwinia amylovora is the major bacterial disease of tribe Maleae, including apple. Among the proteins secreted by this bacterium, HrpNEa, also called harpin, is known to induce hypersensitive response in nonhost plants and to form amyloid oligomers leading to pore opening in the plasma membrane and alteration of membrane homeostasis. To better understand the physiological effects of HrpNEain the host plant, we produced transgenic apple plants expressing HrpNEawith or without a secretion signal peptide (SP). HrpNEaexpressed with a SP was found to be associated within the membrane fraction, in accordance with amyloidogenic properties and the presence of transmembrane domains revealed by in silico analysis. Expression analysis of 28 apple defense-related genes revealed gene modulations in the transgenic line expressing membrane-targeted HrpNEa. While apple transgenic trees displaying a high constitutive expression level of SP-HrpNEashowed a slight reduction of infection frequency after E. amylovora inoculation, there was no decrease in the disease severity. Thus HrpNEaseems to act as an elicitor of host defenses, when localized in the host membrane.
Identification of Blast Resistance in a Core Collection of Foxtail Millet Germplasm
Authors: Sharma Rajan , Girish A. G. , Upadhyaya H. D. , Humayun P. , Babu T. K. , Rao V. P. , Thakur R. P.
Published: October 2013

Blast, also known as leaf spot, caused by Pyricularia grisea (teleomorph: Magnaporthe grisea), is a serious disease affecting both forage and grain production in foxtail millet in India. For the identification of new and diverse sources of blast resistance, a foxtail millet core collection comprising 155 accessions was evaluated against the Patancheru isolate (Fx 57) of M. grisea. In a field screen during 2009 and 2010, 21 accessions were identified with neck and head blast resistance against Fx 57. In a greenhouse screen, 11 of the 155 accessions exhibited seedling leaf blast resistance to the same isolate. Further evaluation of the selected 28 accessions (found resistant to neck and head blast under field conditions during 2009 and 2010 or leaf blast in the greenhouse screen) against four M. grisea isolates (Fx 57, Fx 58, Fx 60, and Fx 62 from Patancheru, Nandyal, Vizianagaram, and Mandya, respectively) led to the identification of 16 accessions with leaf, sheath, neck, and head blast resistance to at least one isolate. Two accessions (ISe 1181 and ISe 1547) were free from head blast infection and showed resistance to leaf (score ≤3.0 on a 1-to-9 scale), neck, and sheath blast (score ≤2.0 on a 1-to-5 scale) against all four isolates. In addition, ISe 1067 and ISe 1575 also exhibited high levels of blast resistance. Blast-resistant accessions with superior agronomic and nutritional quality traits can be evaluated in multilocation yield trials before releasing them for cultivation to farmers.
First Report of Leaf Spot Caused by Alternaria alternata on Marigold (Tagetes erecta) in Beijing, China
Authors: Li Y. , Shen J. , Pan B. H. , Guo M. X. , Wang Q. X. , Ouyang C. B. , Yan D. D. , Cao A. C.
Published: October 2013

Marigold (Tagetes erecta) is an important commercial crop and 200 ha are planted every year in the Beijing district of China. A leaf spot disease of T. erecta was observed during 2012 and 2013 in the Beijing district. The disease was widespread, with 60 to 75% of the fields affected. Leaves of the affected plants had small, brown, necrotic spots on most of the foliage. Yield losses of flowers of up to 20 to 30% were reported. The spots gradually enlarged, becoming irregular in shape, or remained circular, and with concentric rings or zones. In the later stages of infection, the spots coalesced, and the leaves withered, dried, and fell from the plants (4). A fungus was consistently isolated on potato dextrose agar (PDA) from the infected leaves of T. erecta. After 6 days of incubation at 26°C and a 12-h photoperiod, the fungus produced colonies that were flat, with a rough upper surface (2). The conidiophores were short. Conidia varied from 18 × 6 to 47 × 15 μm and were medium to dark brown or olive-brown in color, short beaked, borne in long chains, oval and bean shaped, with 1 to 5 transverse septa and 0 to 2 longitudinal septa. The rDNA of the internal transcribed spacer regions 1 and 2 and the 5.8S gene in seven isolates were amplified using primers ITS1 (5′-TCCGTAGGTGAACCTGCGG-3′) and ITS4 (5′-TCCTCCGCTTATTGATATGC-3′). The nucleotide sequence was the same as isolate No. 7, which was deposited in GenBank (Accession No. KF307207). A BLAST search showed 97% identity with the strain Alternaria alternata GNU-F10 (KC752593). Seven isolates were also confirmed as A. alternata by PCR identification performed by specific primers (C_for/C_rev) of A. alternata (1). Seven isolates were grown on PDA for 2 weeks and the conidia harvested. A 5-μl drop of spore suspension (1 × 105 spores/ml) was placed on each leaflet of 140 detached, surface-sterilized T. erecta leaves. Twenty leaves were inoculated with sterile distilled water as a control. The leaves were incubated in a growth chamber at 80 to 90% relative humidity, 50 to 60 klx/m2 light intensity, and a 12-h photoperiod. After 6 days, leaf spots similar to the original developed at inoculation sites for all isolates and A. alternata was consistently re-isolated. The control leaves remained symptomless. The pathogenicity test was performed three times. Leaf spot of T. erecta caused by Alternaria spp. is well known in Asian countries such as Japan (3). To our knowledge, this is the first report of A. alternata on T. erecta in the Beijing district of China.

References: (1) T. Gat. Plant Dis. 96:1513, 2012. (2) E. Mirkova. J. Phytopathol. 151:323, 2003. (3) K. Tomioka. J. Gen. Plant Pathol. 66:294, 2000. (4) T. Y. Zhang. Page 284 in: Flora Fungorum Sinicorum, Volume 16: Alternaria. Science Press, Beijing, 2003.
Characterization of Iprodione Resistance in Botrytis cinerea from Strawberry and Blackberry
Authors: Grabke Anja , Fernández-Ortuño Dolores , Amiri Achour , Li Xingpeng , Peres Natália A. , Smith Powell , Schnabel Guido
Published: October 2013

Gray mold, caused by the fungal pathogen Botrytis cinerea, is one of the most destructive diseases of strawberry. Control of the disease in commercial fields is largely dependent on the application of fungicides, including the dicarboximide iprodione. Single-spore isolates were collected from strawberry fields in Florida, North Carolina, and South Carolina and subjected to an assay using conidial germination that distinguished sensitive (S) isolates from isolates with various levels of resistance to iprodione. Of the 245 isolates, 1 was highly resistant (HR), 5 were moderately resistant (MR), and 43 had low resistance (LR) to iprodione. LR and MR strains were found in the Florida population and in 9 of 11 locations from North Carolina and South Carolina, indicating that resistance was widespread but accounted for only a relatively small percentage of the B. cinerea population. Sequence analysis of the target gene bos1, which codes for a class III histidine kinase, revealed that the MR phenotype was associated with Q369P and N373S mutations and that the LR phenotype was associated with either a I365S or a I365N mutation. The I365S and I365N mutations were also present in five additionally included HR isolates from North Carolina and South Carolina blackberry fields and one HR isolate from a Virginia strawberry field but no mutation or mutation combinations in bos1 were uniquely associated with the HR phenotype. Expression analysis of bos1 in S and HR isolates did not reveal convincing evidence of the gene's involvement in HR resistance either. The six HR isolates had three different phenotypes with respect to their sensitivity to fludioxonil; two were S, two were LR, and two were MR. The fludioxonil LR and MR isolates were also resistant to tolnaftate, an indication of multidrug efflux pump activity. These data suggest that, in addition to point mutations in bos1, drug efflux pump activity and potentially a third mechanism of resistance may be contributing to the iprodione HR phenotype. Detached fruit studies showed that field rates of Rovral 4 Flowable (iprodione) did not control iprodione MR and HR isolates.
Competency-based Education in Anesthesiology
Authors: Ebert Thomas J. , Fox Chris A.
Published: October 2013

The Accreditation Council for Graduate Medical Education is transitioning to a competency-based system with milestones to measure progress and define success of residents. The confines of the time-based residency will be relaxed. Curriculum must be redesigned and assessments will need to be precise and in-depth. Core anesthesiology faculty will be identified and will be the “trained observers” of the residents’ progress. There will be logistic challenges requiring creative management by program directors. There may be residents who achieve “expert” status earlier than the required 36 months of clinical anesthesia education, whereas others may struggle to achieve acceptable status and will require additional education time. Faculty must accept both extremes without judgment. Innovative new educational opportunities will need to be created for fast learners. Finally, it will be important that residents embrace this change. This will require programs to clearly define the specific aims and measurement endpoints for advancement and success.
Ghrelin and Obestatin Levels in Children With Failure to Thrive and Obesity
Authors: Wali Prateek , King Jeremy , He Zhaoping , Tonb Dalal , Horvath Karoly
Published: October 2013

Objectives:

Ghrelin and obestatin are 2 gastric hormones with opposite effects on food intake and body weight. We investigated plasma ghrelin and obestatin in children with failure to thrive (FTT) and obesity as compared with age‐matched controls.

Methods:

A total of 63 children were included in the study: 13 with FTT, 17 with obesity, and 33 age‐matched controls. Children fasted for at least 8 hours before specimen collection. Both hormones were measured using commercially available enzyme immunoassay kits.

Results:

Ghrelin and obestatin levels in children with FTT were not significantly different from that of the age‐matched controls (P >0.05). In children with obesity, the total ghrelin levels were significantly lower (P = 0.0003) and the obestatin levels significantly higher (P = 0.029) compared with those in controls. In the control group, the fasting ghrelin level was significantly higher in the younger (<3 years) than in the older children (>3 years; P = 0.0004). Obestatin levels correlated positively with weight‐for‐age percentiles in the obese group (P = 0.011) and negatively in the control group >3 years (P = 0.019).

Conclusions:

Compared with the levels in age‐matched controls, fasting ghrelin and obestatin levels did not differ significantly in children with FTT. In the children with obesity, the decreased ghrelin and increased obestatin levels suggest a possible adaptive process to positive energy balance. Ghrelin had pronounced age‐related changes, and obestatin was associated with the weight status. This may suggest that these 2 hormones use different mechanisms to regulate energy balance and weight.
Traumatic brain injury–induced alterations in peripheral immunity
Authors: Schwulst Steven J. , Trahanas Diane M. , Saber Rana , Perlman Harris
Published: October 2013

BACKGROUND

The complex alterations that occur in peripheral immunity after traumatic brain injury (TBI) have been poorly characterized to date. The purpose of this study was to determine the temporal changes in the peripheral immune response after TBI in a murine model of closed head injury.

METHODS

C57Bl/6 mice underwent closed head injury via a weight drop technique (n = 5) versus sham injury (n = 3) per time point. Blood, spleen, and thymus were collected, and immune phenotype, cytokine expression, and antibody production were determined via flow cytometry and multiplex immunoassays at 1, 3, 7, 14, 30, and 60 days after injury.

RESULTS

TBI results in acute and chronic changes in both the innate and adaptive immune response. TBI resulted in a striking loss of thymocytes as early as 3 days after injury (2.1 × 107 TBI vs. 5.6 × 107 sham, p = 0.001). Similarly, blood monocyte counts were markedly diminished as early as 24 hours after TBI (372 per deciliter TBI vs. 1359 per deciliter sham, p = 0.002) and remained suppressed throughout the first month after injury. At 60 days after injury, monocytes were polarized toward an anti-inflammatory (M2) phenotype. TBI also resulted in diminished interleukin 12 expression from Day 14 after injury throughout the remainder of the observation period.

CONCLUSION

TBI results in temporal changes in both the peripheral and the central immune systems culminating in an overall immune suppressed phenotype and anti-inflammatory milieu.
Restraint stress aggravates rat kidney injury caused by a crush injury through endoplasmic reticulum stress
Authors: Geng Jing , Zhang Xiao Jing , Ma Chun Ling , Li Ying Min , Zhang Guo Zhong , Ma Ru Fei , Zhang Yue , Cong Bin
Published: October 2013

BACKGROUND

The present study aimed to determine whether restraint stress aggravates kidney injury caused by a crush injury through endoplasmic reticulum stress (ERS).

METHODS

In this study, Sprague-Dawley rat restraint stress, crush injury, and stressful injury models consisting of restraint stress and crush injury were established. An ERS inhibitor, Salubrinal (Sal), was administered intraperitoneally 30 minutes before induction of daily injury in the stressful injury group. At the end of the experimental procedures, plasma levels of noradrenaline and adrenaline, creatine phosphokinase, creatinine, and blood urea nitrogen were measured. Kidneys were harvested, and paraffin-embedded sections of kidney tissues were processed for hematoxylin-eosin staining and TUNEL assay to verify pathologic changes. Western blot was used to determine the protein levels of glucose-regulated protein 78, CCAAT/enhancer-binding protein-homologous protein, caspase 12, caspase 3, and MCP-1 in kidney specimens.

RESULTS

Compared with crush injury, the most significant changes in kidney injury occurred in the stressful injury group, which was inhibited by Sal. The results suggested that restraint stress aggravates kidney injury caused by a crush injury, and the mechanism might involve ERS. Further study showed that double attacks induced a significant increase in the levels of glucose-regulated protein 78, CCAAT/enhancer-binding protein-homologous protein, caspase 12, and caspase 3, which was inhibited by Sal. The same changes were observed using the TUNEL assay. Double attacks also induced an increased expression of the proinflammatory cytokine, MCP-1, which was inhibited by Sal.

CONCLUSION

Apoptosis and inflammation induced by ERS are important mechanisms by which restraint stress aggravates kidney injury caused by a crush injury.
Long-term outcome analysis of liver transplantation for severe hepatic trauma
Authors: Kaltenborn Alexander , Reichert Benedikt , Bourg Catherine M. , Becker Thomas , Lehner Frank , Klempnauer Jürgen , Schrem Harald
Published: October 2013

BACKGROUND

Liver transplantation (LTX) for severe hepatic trauma and its sequelae is a rare but potentially lifesaving option at the far end of the operative spectrum.

METHODS

This study analyzes 12 cases with LTX for hepatic trauma and its consequences from two transplant centers. A total of 2,701 consecutive liver transplants unrelated to trauma served as a control group. χ2 and Mann-Whitney U-tests, Kaplan-Meier analysis with log-rank tests, and Cox regression analysis were applied. Addressed were issues before, during, and after LTX. Major study end points were patient and graft survival.

RESULTS

The posttrauma transplant recipients are significantly younger (p = 0.014), with a significantly shorter graft survival (p = 0.038), resulting in a significantly higher retransplantation rate (p = 0.043). Of the 12 patients, 11 underwent surgical treatment for hepatic trauma before LTX with 7 of 12 patients experiencing liver necrosis at the time of LTX. Short-term survival and long-term survival are not significantly different between trauma and nontrauma patients. Severity of liver trauma (Moore Score) and concomitant injuries (Injury Severity Score [ISS]) have no significant impact on patient and graft survival. Four patients with hepatic trauma were treated with two-stage LTX with anhepatic phases between 14 hours and 28 hours. Two of those patients reached long-term survival (20–22 years).

CONCLUSION

LTX for severe liver trauma and its consequences seems justified in extreme cases. The high frequency of liver necrosis at the time of LTX may indicate possible shortcomings in liver packing technique or liver resection for hemorrhage control. Thus, severe hepatic trauma requires treatment by experienced liver surgeons and emergency physicians.

LEVEL OF EVIDENCE

Therapeutic study, level IV.
Group VIB Ca2+-independent phospholipase A2γ is associated with acute lung injury following trauma and hemorrhagic shock
Authors: Morishita Koji , Aiboshi Junichi , Kobayashi Tetsuyuki , Yokoyama Yuri , Mikami Saori , Kumagai Jiro , Onisawa Keiko , Otomo Yasuhiro
Published: October 2013

BACKGROUND

Gut-derived mediators are carried via mesenteric lymph duct into systemic circulation after trauma/hemorrhagic shock (T/HS), thus leading to acute lung injury (ALI)/multiple-organ dysfunction syndrome. Phospholipase A2 (PLA2) is a key enzyme for the production of lipid mediators in posthemorrhagic shock mesenteric lymph (PHSML). However, the precise functions of PLA2 subtype, such as cytosolic PLA2, secretory PLA2, and Ca2+-independent PLA2, in the acute phase of inflammation have remained unclear. Our previous study has suggested that the activation of Group VIB Ca2+-independent PLA2γ (iPLA2γ) may be associated with increased lyso-phosphatidylcholines (LPCs) in the PHSML. Therefore, our purpose was to verify the role of iPLA2γ on the production of 2-polyunsaturated LPC species and the pathogenesis of T/HS-induced ALI using an iPLA2γ-specific inhibitor, R-(E)-6-(bromoethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one (R-BEL).

METHODS

Male Sprague-Dawley rats were anesthetized and cannulated in blood vessels and mesenteric lymph duct. Animals in the T/HS group underwent a midline laparotomy plus hemorrhagic shock (mean arterial pressure, 35 mm Hg, 30 minutes) and 2-hour resuscitation with shed blood and 2× normal saline. Trauma/sham shock rats were performed the identical procedure without hemorrhage. R-BEL or DMSO was administered 30 minutes before T/HS or trauma/sham shock. Polyunsaturated LPCs and arachidonic acid in the PHSML were analyzed with a liquid chromatography/electrospray ionization–mass spectrometry. Furthermore, ALI was assessed by lung vascular permeability, myeloperoxidase activity, and histology.

RESULTS

T/HS increased 2-polyunsaturated LPCs and arachidonic acid in the PHSML. The R-BEL pretreatment significantly decreased these lipids and also inhibited ALI.

CONCLUSION

The iPLA2γ enzyme is possibly involved in the pathogenesis of ALI following T/HS through the mesenteric lymph pathway.
Evaluation of resuscitation fluids on endothelial glycocalyx, venular blood flow, and coagulation function after hemorrhagic shock in rats
Authors: Torres Luciana N. , Sondeen Jill L. , Ji Lisa , Dubick Michael A. , Filho Ivo Torres
Published: October 2013

BACKGROUND

Endothelial glycocalyx (EG) plays an essential role in endothelium integrity and may be compromised by hemorrhagic shock. The effects of currently available resuscitation fluids such as Hextend (HEX) or lactated Ringer’s solution (LR) on vascular function and coagulation are not well understood. The aim of the present study was to compare the effects of fresh frozen plasma (FFP) with HEX or LR in their ability to repair EG structure, promote volume expansion, increase blood flow, and prevent coagulopathy.

METHODS

A total of 121 microvessels from cremaster muscle were studied in 32 anesthetized instrumented rats. After baseline systemic and microvascular measurements, 40% hemorrhage followed by resuscitation was performed, and measurements were repeated. Coagulation was evaluated using ROTEM to assay clot formation time, clotting time, firmness, strength, and lysis. Velocity and “platelet component” of strength were calculated. Fluorescein isothiocyanate or Texas Red bound to Dextrans was injected to estimate EG thickness in vivo.

RESULTS

Respiratory rate, blood pH, base excess, and lactate returned to near-baseline levels in all treatments. Hemodilution caused by LR and HEX decreased firmness, prolonged clotting time, and lowered platelet counts. EG thickness in HEX- and LR-treated rats was 50% lower, and plasma syndecan 1 was 50% higher than sham and FFP groups. Blood flow and shear rate were restored in the HEX group. Resuscitation with FFP improved coagulation and blood flow.

CONCLUSION

Our findings support the concept of cardiovascular and microvascular stabilization by infused FFP, in which the increase in microvascular perfusion associated with restored EG is essential for an optimal resuscitation strategy.
Pulsed dosed delivery of oxygen in mechanically ventilated pigs with acute lung injury
Authors: Gustafson Joshua D. , Yang Sung , Blakeman Thomas Chris , Dorlac Warren C. , Branson Richard
Published: October 2013

BACKGROUND

Acute lung injury (ALI) is a condition that leads to impaired oxygen delivery. We demonstrated previously that using a portable oxygen concentrator (POC) with pulsed dose delivery of oxygen is an alternative option to conserve oxygen while still maintaining adequate oxygen delivery in a mechanical model. We hypothesized that using a modified POC, pulsed dose oxygen delivery can provide adequate oxygenation in an animal model.

METHODS

In a crossover study, we induced ALI in 15 pigs using an oleic acid model. We ventilated the pigs using equipment that is used by Critical Care Air Transport Teams of the US Air Force. We compared oxygen delivery using a POC in both continuous flow and pulsed dose modes, while in both volume-control and pressure-control mechanical ventilation.

RESULTS

The PaO2/FIO2 ratios were increased in both the continuous flow and pulsed dose delivery for volume control and pressure control. In volume control, the pulsed dose demonstrated a significant increase in the PaO2/FIO2 ratio (168.8 [96.1] vs. 91.7 [65.4], p = 0.002) compared with continuous flow. However, this was not seen in pressure-control ventilation (89.0 [74.5] vs. 79.1 [65.4], p = 0.67).

CONCLUSION

We were able to demonstrate that oxygen delivery using a POC in mechanically ventilated pigs with ALI is feasible. We were also able to demonstrate that pulsed dose delivery from a POC is superior to continuous flow oxygen delivery for oxygenation in ALI, when using volume control. We propose that this is a safe alternative to conserve oxygen in the transport of critically ill patients.
A novel taxonomic marker that discriminates between morphologically complex actinomycetes
Authors: Girard Geneviève , Traag Bjørn A. , Sangal Vartul , Mascini Nadine , Hoskisson Paul A. , Goodfellow Michael , van Wezel Gilles P.
Published: October 2013

In the era when large whole genome bacterial datasets are generated routinely, rapid and accurate molecular systematics is becoming increasingly important. However, 16S ribosomal RNA sequencing does not always offer sufficient resolution to discriminate between closely related genera. The SsgA-like proteins are developmental regulatory proteins in sporulating actinomycetes, whereby SsgB actively recruits FtsZ during sporulation-specific cell division. Here, we present a novel method to classify actinomycetes, based on the extraordinary way the SsgA and SsgB proteins are conserved. The almost complete conservation of the SsgB amino acid (aa) sequence between members of the same genus and its high divergence between even closely related genera provides high-quality data for the classification of morphologically complex actinomycetes. Our analysis validatesKitasatosporaas a sister genus toStreptomycesin the family Streptomycetaceae and suggests thatMicromonospora,SalinisporaandVerrucosisporamay represent different clades of the same genus. It is also apparent that the aa sequence of SsgA is an accurate determinant for the ability of streptomycetes to produce submerged spores, dividing the phylogenetic tree of streptomycetes into liquid-culture sporulation and no liquid-culture sporulation branches. A new phylogenetic tree of industrially relevant actinomycetes is presented and compared with that based on 16S rRNA sequences.
MicroRNA-independent roles of the RNase III enzymes Drosha and Dicer
Authors: Johanson Timothy M. , Lew Andrew M. , Chong Mark M. W.
Published: October 2013

The ribonuclease III enzymes Drosha and Dicer are renowned for their central roles in the biogenesis of microRNAs (miRNAs). For many years, this has overshadowed the true versatility and importance of these enzymes in the processing of other RNA substrates. For example, Drosha also recognizes and cleaves messenger RNAs (mRNAs), and potentially ribosomal RNA. The cleavage of mRNAs occurs via recognition of secondary stem-loop structures similar to miRNA precursors, and is an important mechanism of repressing gene expression, particularly in progenitor/stem cell populations. On the other hand, Dicer also has critical roles in genome regulation and surveillance. These include the production of endogenous small interfering RNAs from many sources, and the degradation of potentially harmful short interspersed element and viral RNAs. These findings have sparked a renewed interest in these enzymes, and their diverse functions in biology.
A conserved C-terminal sequence of high-risk cutaneous beta-human papillomavirus E6 proteins alters localization and signalling of β1-integrin to promote cell migration
Authors: Holloway Amy , Storey Alan
Published: October 2013

Beta-human papillomaviruses (β-HPV) infect cutaneous epithelia, and accumulating evidence suggests that the virus may act as a co-factor with UV-induced DNA damage in the development and progression of non-melanoma skin cancer, although the molecular mechanisms involved are poorly understood. The E6 protein of cutaneous β-HPV types encodes functions consistent with a role in tumorigenesis, and E6 expression can result in papilloma formation in transgenic animals. The E6 proteins of high-risk α-HPV types, which are associated with the development of anogenital cancers, have a conserved 4 aa motif at their extreme C terminus that binds to specific PDZ domain-containing proteins to promote cell invasion. Likewise, the high-risk β-HPVs HPV5 and HPV8 E6 proteins also share a conserved C-terminal motif, but this is markedly different from that of α-HPV types, implying functional differences. Using binding and functional studies, we have shown that β-HPV E6 proteins target β1-integrin using this C-terminal motif. E6 expression reduced membrane localization of β1-integrin, but increased overall levels of β1-integrin protein and its downstream effector focal adhesion kinase in human keratinocytes. Altered β1-integrin localization due to E6 expression was associated with actin cytoskeleton rearrangement and increased cell migration that was abolished by point mutations in the C-terminal motif of E6. We concluded that modulation of β1-integrin signalling by E6 proteins may contribute towards the pathogenicity of these β-HPV types.
Perceived value of pasta in Greece and Romania
Authors: Dumitrescu Claudia , Nganje William , J. Shultz Clifford
Published: October 2013

Purpose

– This study aims to provide international pasta marketers with a better understanding of how consumers perceive product value, which enables them to create and deliver value. The effects of COO, price, and content on purchase intentions are assessed.

Design/methodology/approach

– Data were collected via the survey method in Romania and Greece. Using a random utility discrete choice model, the authors test five hypotheses.

Findings

– Overall, Romanian and Greek individuals are less likely to buy US pasta; nevertheless, the likelihood that US or Italian pasta is purchased increases when this product is made from durum wheat versus soft wheat. Differences in purchase intentions due to age, gender, education, income, and nationality are also found.

Research limitations/implications

– The results have important implications for international pasta marketers, as it helps them to better understand the perceived pasta value and to position this product effectively in Greek and Romanian markets. Future studies should examine wider pasta market segmentation in the Balkans.

Originality/value

– This study contributes to the value literature by providing a framework of perceived value of foreign food products. Also, addressing concerns expressed in the literature, this study examines the COO effects on purchase intentions in a multi-cue context, focusing on low-involvement food products such as pasta. Because individual preferences for COO vary widely, the need for empirical evidence to complement theory is critical, and this is the first study with regard to Greek and Romanian consumers' intentions to buy foreign pasta.