bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Anterior Cruciate Ligament Injury
Authors: Smith Helen C. , Vacek Pamela , Johnson Robert J. , Slauterbeck James R. , Hashemi Javad , Shultz Sandra , Beynnon Bruce D.
Published: November 2011

Context: Injuries to the anterior cruciate ligament (ACL) are immediately disabling and are associated with long-term consequences, such as posttraumatic osteoarthritis. It is important to have a comprehensive understanding of all possible risk factors for ACL injury to identify individuals who are at risk for future injuries and to provide an appropriate level of counseling and programs for prevention.

Objective: This review, part 2 of a 2-part series, highlights what is known and still unknown regarding hormonal, genetic, cognitive function, previous injury, and extrinsic risk factors for ACL injury.

Data Sources: Studies were identified from MEDLINE (1951–March 2011) using the MeSH terms anterior cruciate ligament, knee injury, and risk factors. The bibliographies of relevant articles and reviews were cross-referenced to complete the search.

Study Selection: Prognostic case-control and prospective cohort study designs to evaluate risk factors for ACL injury were included in this review.

Results: A total of 50 case-control and prospective cohort articles were included in parts 1 and 2. Twenty-one focused on hormonal, genetic, cognitive function, previous injury, and extrinsic risk factors.

Conclusions: Several risk factors are associated with increased risk of suffering ACL injury—such as female sex, prior reconstruction of the ACL, and familial predisposition. These risk factors most likely act in combination with the anatomic factors reviewed in part 1 of this series to influence the risk of suffering ACL injury.
Three-dimensional modeling of chromatin structure from interaction frequency data using Markov chain Monte Carlo sampling
Authors: Rousseau Mathieu , Fraser James , Ferraiuolo Maria A , Dostie Josée , Blanchette Mathieu
Published: November 2011

Background

Long-range interactions between regulatory DNA elements such as enhancers, insulators and promoters play an important role in regulating transcription. As chromatin contacts have been found throughout the human genome and in different cell types, spatial transcriptional control is now viewed as a general mechanism of gene expression regulation. Chromosome Conformation Capture Carbon Copy (5C) and its variant Hi-C are techniques used to measure the interaction frequency (IF) between specific regions of the genome. Our goal is to use the IF data generated by these experiments to computationally model and analyze three-dimensional chromatin organization.

Results

We formulate a probabilistic model linking 5C/Hi-C data to physical distances and describe a Markov chain Monte Carlo (MCMC) approach called MCMC5C to generate a representative sample from the posterior distribution over structures from IF data. Structures produced from parallel MCMC runs on the same dataset demonstrate that our MCMC method mixes quickly and is able to sample from the posterior distribution of structures and find subclasses of structures. Structural properties (base looping, condensation, and local density) were defined and their distribution measured across the ensembles of structures generated. We applied these methods to a biological model of human myelomonocyte cellular differentiation and identified distinct chromatin conformation signatures (CCSs) corresponding to each of the cellular states. We also demonstrate the ability of our method to run on Hi-C data and produce a model of human chromosome 14 at 1Mb resolution that is consistent with previously observed structural properties as measured by 3D-FISH.

Conclusions

We believe that tools like MCMC5C are essential for the reliable analysis of data from the 3C-derived techniques such as 5C and Hi-C. By integrating complex, high-dimensional and noisy datasets into an easy to interpret ensemble of three-dimensional conformations, MCMC5C allows researchers to reliably interpret the result of their assay and contrast conformations under different conditions.

Availability

http://Dostielab.biochem.mcgill.ca
POPISK: T-cell reactivity prediction using support vector machines and string kernels
Authors: Tung Chun-Wei , Ziehm Matthias , Kämper Andreas , Kohlbacher Oliver , Ho Shinn-Ying
Published: November 2011

Background

Accurate prediction of peptide immunogenicity and characterization of relation between peptide sequences and peptide immunogenicity will be greatly helpful for vaccine designs and understanding of the immune system. In contrast to the prediction of antigen processing and presentation pathway, the prediction of subsequent T-cell reactivity is a much harder topic. Previous studies of identifying T-cell receptor (TCR) recognition positions were based on small-scale analyses using only a few peptides and concluded different recognition positions such as positions 4, 6 and 8 of peptides with length 9. Large-scale analyses are necessary to better characterize the effect of peptide sequence variations on T-cell reactivity and design predictors of a peptide's T-cell reactivity (and thus immunogenicity). The identification and characterization of important positions influencing T-cell reactivity will provide insights into the underlying mechanism of immunogenicity.

Results

This work establishes a large dataset by collecting immunogenicity data from three major immunology databases. In order to consider the effect of MHC restriction, peptides are classified by their associated MHC alleles. Subsequently, a computational method (named POPISK) using support vector machine with a weighted degree string kernel is proposed to predict T-cell reactivity and identify important recognition positions. POPISK yields a mean 10-fold cross-validation accuracy of 68% in predicting T-cell reactivity of HLA-A2-binding peptides. POPISK is capable of predicting immunogenicity with scores that can also correctly predict the change in T-cell reactivity related to point mutations in epitopes reported in previous studies using crystal structures. Thorough analyses of the prediction results identify the important positions 4, 6, 8 and 9, and yield insights into the molecular basis for TCR recognition. Finally, we relate this finding to physicochemical properties and structural features of the MHC-peptide-TCR interaction.

Conclusions

A computational method POPISK is proposed to predict immunogenicity with scores which are useful for predicting immunogenicity changes made by single-residue modifications. The web server of POPISK is freely available athttp://iclab.life.nctu.edu.tw/POPISK.
Flavivirus NS3 and NS5 proteins interaction network: a high-throughput yeast two-hybrid screen
Authors: Le Breton Marc , Meyniel-Schicklin Laurène , Deloire Alexandre , Coutard Bruno , Canard Bruno , de Lamballerie Xavier , Andre Patrice , Rabourdin-Combe Chantal , Lotteau Vincent , Davoust Nathalie
Published: November 2011

Background

The genus Flavivirus encompasses more than 50 distinct species of arthropod-borne viruses, including several major human pathogens, such as West Nile virus, yellow fever virus, Japanese encephalitis virus and the four serotypes of dengue viruses (DENV type 1-4). Each year, flaviviruses cause more than 100 million infections worldwide, some of which lead to life-threatening conditions such as encephalitis or haemorrhagic fever. Among the viral proteins, NS3 and NS5 proteins constitute the major enzymatic components of the viral replication complex and are essential to the flavivirus life cycle.

Results

We report here the results of a high-throughput yeast two-hybrid screen to identify the interactions between human host proteins and the flavivirus NS3 and NS5 proteins. Using our screen results and literature curation, we performed a global analysis of the NS3 and NS5 cellular targets based on functional annotation with the Gene Ontology features. We finally created the first flavivirus NS3 and NS5 proteins interaction network and analysed the topological features of this network. Our proteome mapping screen identified 108 human proteins interacting with NS3 or NS5 proteins or both. The global analysis of the cellular targets revealed the enrichment of host proteins involved in RNA binding, transcription regulation, vesicular transport or innate immune response regulation.

Conclusions

We proposed that the selective disruption of these newly identified host/virus interactions could represent a novel and attractive therapeutic strategy in treating flavivirus infections. Our virus-host interaction map provides a basis to unravel fundamental processes about flavivirus subversion of the host replication machinery and/or immune defence strategy.
Parthenocarpic potential in Capsicum annuumL. is enhanced by carpelloid structures and controlled by a single recessive gene
Authors: Tiwari Aparna , Vivian-Smith Adam , Voorrips Roeland E , Habets Myckel EJ , Xue Lin B , Offringa Remko , Heuvelink Ep
Published: November 2011

Background

Parthenocarpy is a desirable trait in Capsicum annuum production because it improves fruit quality and results in a more regular fruit set. Previously, we identified several C. annuum genotypes that already show a certain level of parthenocarpy, and the seedless fruits obtained from these genotypes often contain carpel-like structures. In the Arabidopsis bel1 mutant ovule integuments are transformed into carpels, and we therefore carefully studied ovule development in C. annuum and correlated aberrant ovule development and carpelloid transformation with parthenocarpic fruit set.

Results

We identified several additional C. annuum genotypes with a certain level of parthenocarpy, and confirmed a positive correlation between parthenocarpic potential and the development of carpelloid structures. Investigations into the source of these carpel-like structures showed that while the majority of the ovules in C. annuum gynoecia are unitegmic and anatropous, several abnormal ovules were observed, abundant at the top and base of the placenta, with altered integument growth. Abnormal ovule primordia arose from the placenta and most likely transformed into carpelloid structures in analogy to the Arabidopsis bel1 mutant. When pollination was present fruit weight was positively correlated with seed number, but in the absence of seeds, fruit weight proportionally increased with the carpelloid mass and number. Capsicum genotypes with high parthenocarpic potential always showed stronger carpelloid development. The parthenocarpic potential appeared to be controlled by a single recessive gene, but no variation in coding sequence was observed in a candidate gene CaARF8.

Conclusions

Our results suggest that in the absence of fertilization most C. annuum genotypes, have parthenocarpic potential and carpelloid growth, which can substitute developing seeds in promoting fruit development.
Characterization of highly efficient heavy-ion mutagenesis in Arabidopsis thaliana
Authors: Kazama Yusuke , Hirano Tomonari , Saito Hiroyuki , Liu Yang , Ohbu Sumie , Hayashi Yoriko , Abe Tomoko
Published: November 2011

Background

Heavy-ion mutagenesis is recognised as a powerful technology to generate new mutants, especially in higher plants. Heavy-ion beams show high linear energy transfer (LET) and thus more effectively induce DNA double-strand breaks than other mutagenic techniques. Previously, we determined the most effective heavy-ion LET (LETmax: 30.0 keV μm-1) for Arabidopsis mutagenesis by analysing the effect of LET on mutation induction. However, the molecular structure of mutated DNA induced by heavy ions with LETmax remains unclear. Knowledge of the structure of mutated DNA will contribute to the effective exploitation of heavy-ion beam mutagenesis.

Results

Dry Arabidopsis thaliana seeds were irradiated with carbon (C) ions with LETmax at a dose of 400 Gy and with LET of 22.5 keV μm-1 at doses of 250 Gy or 450 Gy. The effects on mutation frequency and alteration of DNA structure were compared. To characterise the structure of mutated DNA, we screened the well-characterised mutants elongated hypocotyls (hy) and glabrous (gl) and identified mutated DNA among the resulting mutants by high-resolution melting curve, PCR and sequencing analyses. The mutation frequency induced by C ions with LETmax was two-fold higher than that with 22.5 keV μm-1 and similar to the mutation frequency previously induced by ethyl methane sulfonate. We identified the structure of 22 mutated DNAs. Over 80% of the mutations caused by C ions with both LETs were base substitutions or deletions/insertions of less than 100 bp. The other mutations involved large rearrangements.

Conclusions

The C ions with LETmax showed high mutation efficiency and predominantly induced base substitutions or small deletions/insertions, most of which were null mutations. These small alterations can be determined by single-nucleotide polymorphism (SNP) detection systems. Therefore, C ions with LETmax might be useful as a highly efficient reverse genetic system in conjunction with SNP detection systems, and will be beneficial for forward genetics and plant breeding.
Improvement of antibiotic activity of Xenorhabdus bovienii by medium optimization using response surface methodology
Authors: Wang Yonghong , Fang Xiangling , An Fengqiu , Wang Guohong , Zhang Xing
Published: November 2011

Background

The production of secondary metabolites with antibiotic properties is a common characteristic to entomopathogenic bacteria Xenorhabdus spp. These metabolites not only have diverse chemical structures but also have a wide range of bioactivities with medicinal and agricultural interests such as antibiotic, antimycotic and insecticidal, nematicidal and antiulcer, antineoplastic and antiviral. It has been known that cultivation parameters are critical to the secondary metabolites produced by microorganisms. Even small changes in the culture medium may not only impact the quantity of certain compounds but also the general metabolic profile of microorganisms. Manipulating nutritional or environmental factors can promote the biosynthesis of secondary metabolites and thus facilitate the discovery of new natural products. This work was conducted to evaluate the influence of nutrition on the antibiotic production of X. bovienii YL002 and to optimize the medium to maximize its antibiotic production.

Results

Nutrition has high influence on the antibiotic production of X. bovienii YL002. Glycerol and soytone were identified as the best carbon and nitrogen sources that significantly affected the antibiotic production using one-factor-at-a-time approach. Response surface methodology (RSM) was applied to optimize the medium constituents (glycerol, soytone and minerals) for the antibiotic production of X. bovienii YL002. Higher antibiotic activity (337.5 U/mL) was obtained after optimization. The optimal levels of medium components were (g/L): glycerol 6.90, soytone 25.17, MgSO4·7H2O 1.57, (NH4)2SO4 2.55, KH2PO4 0.87, K2HPO4 1.11 and Na2SO4 1.81. An overall of 37.8% increase in the antibiotic activity of X. bovienii YL002 was obtained compared with that of the original medium.

Conclusions

To the best of our knowledge, there are no reports on antibiotic production of X. boviebii by medium optimization using RSM. The results strongly support the use of RSM for medium optimization. The optimized medium not only resulted in a 37.8% increase of antibiotic activity, but also reduced the numbers of experiments. The chosen method of medium optimization was efficient, simple and less time consuming. This work will be useful for the development of X. bovienii cultivation process for efficient antibiotic production on a large scale, and for the development of more advanced control strategies on plant diseases.
Fetal calf serum heat inactivation and lipopolysaccharide contamination influence the human T lymphoblast proteome and phosphoproteome
Authors: Rahman Hazir , Qasim Muhammad , Schultze Frank C , Oellerich Michael , R Asif Abdul
Published: November 2011

Background

The effects of fetal calf serum (FCS) heat inactivation and bacterial lipopolysaccharide (LPS) contamination on cell physiology have been studied, but their effect on the proteome of cultured cells has yet to be described. This study was undertaken to investigate the effects of heat inactivation of FCS and LPS contamination on the human T lymphoblast proteome. Human T lymphoblastic leukaemia (CCRF-CEM) cells were grown in FCS, either non-heated, or heat inactivated, having low (< 1 EU/mL) or regular (< 30 EU/mL) LPS concentrations. Protein lysates were resolved by 2-DE followed by phospho-specific and silver nitrate staining. Differentially regulated spots were identified by nano LC ESI Q-TOF MS/MS analysis.

Results

A total of four proteins (EIF3M, PRS7, PSB4, and SNAPA) were up-regulated when CCRF-CEM cells were grown in media supplemented with heat inactivated FCS (HE) as compared to cells grown in media with non-heated FCS (NHE). Six proteins (TCPD, ACTA, NACA, TCTP, ACTB, and ICLN) displayed a differential phosphorylation pattern between the NHE and HE groups. Compared to the low concentration LPS group, regular levels of LPS resulted in the up-regulation of three proteins (SYBF, QCR1, and SUCB1).

Conclusion

The present study provides new information regarding the effect of FCS heat inactivation and change in FCS-LPS concentration on cellular protein expression, and post-translational modification in human T lymphoblasts. Both heat inactivation and LPS contamination of FCS were shown to modulate the expression and phosphorylation of proteins involved in basic cellular functions, such as protein synthesis, cytoskeleton stability, oxidative stress regulation and apoptosis. Hence, the study emphasizes the need to consider both heat inactivation and LPS contamination of FCS as factors that can influence the T lymphoblast proteome.
Retrospective analysis for thirty-nine patients with solitary fibrous tumor of pleura and review of the literature
Authors: Guo Wei , Xiao Hua-Liang , Jiang Yao-Guang , Wang Ru-Wen , Zhao Yun-Ping , Ma Zheng , Niu Hui-Jun
Published: November 2011

Background

Solitary fibrous tumor of the pleura (SFTP) is an uncommon neoplasm arising from mesenchymal cells. The aim of this study is to summarize the experience and the outcome of the surgical treatment for 39 cases of SFTP.

Methods

From January 2004 to December 2008, 39 patients underwent surgical resection of SFTP in our department. All patients had clinical follow-up by the same team of surgeons. The mean follow-up was 40.3 months.

Results

A local removal of the neoplasm was accomplished by video-assisted thoracic surgery (VATS) in 9 patients (group A) and by thoracotomy in 30 patients (group B) respectively. Comparing with group B, operations in group A took significantly less operative time, blood loss and spent less time in the intensive care unit and hospital. All specimens were positive for CD34 and Bcl-2. One patient developed recurrence, and the remaining 38 patients are alive and disease free at the end of follow-up.

Conclusions

Malignant SFTP still had the potential recurrence. VATS represents the more acceptable choice for the selected patients with SFTP.
Unique phenotype in a patient with CHARGE syndrome
Authors: Jain Shobhit , Kim Hyung-Goo , Lacbawan Felicitas , Meliciani Irene , Wenzel Wolfgang , Kurth Ingo , Sharma Josefina , Schoeneman Morris , Ten Svetlana , Layman Lawrence C , Jacobson-Dickman Elka
Published: November 2011

CHARGE is a phenotypically heterogeneous autosomal dominant disorder recognized as a cohesive syndrome since the identification of CHD7 as a genetic etiology. Classic features include: Coloboma, Heart defects, Atresia choanae, Retarded growth and development, Genitourinary abnormalities, and Ear anomalies and/or deafness. With greater accessibility to genetic analysis, a wider spectrum of features are emerging, and overlap with disorders such as DiGeorge syndrome, Kallmann syndrome, and Hypoparathyroidism Sensorineural Deafness and Renal Disease syndrome, is increasingly evident. We present a patient with a unique manifestation of CHARGE syndrome, including primary hypoparathyroidism and a limb anomaly; to our knowledge, he is also the first CHARGE subject reported with bilateral multicystic dysplastic kidneys. Furthermore, with structural modeling and murine expression studies, we characterize a putative CHD7 G744S missense mutation. Our report continues to expand the CHARGE phenotype and highlights that stringent fulfillment of conventional criteria should not strictly guide genetic analysis.
Expression and reactivation of HIV in a chemokine induced model of HIV latency in primary resting CD4+ T cells
Authors: Saleh Suha , Wightman Fiona , Ramanayake Saumya , Alexander Marina , Kumar Nitasha , Khoury Gabriela , Pereira Cândida , Purcell Damian , Cameron Paul U , Lewin Sharon R
Published: November 2011

Background

We recently described that HIV latent infection can be established in vitro following incubation of resting CD4+ T-cells with chemokines that bind to CCR7. The main aim of this study was to fully define the post-integration blocks to virus replication in this model of CCL19-induced HIV latency.

Results

High levels of integrated HIV DNA but low production of reverse transcriptase (RT) was found in CCL19-treated CD4+ T-cells infected with either wild type (WT) NL4.3 or single round envelope deleted NL4.3 pseudotyped virus (NL4.3- Δenv). Supernatants from CCL19-treated cells infected with either WT NL4.3 or NL4.3- Δenv did not induce luciferase expression in TZM-bl cells, and there was no expression of intracellular p24. Following infection of CCL19-treated CD4+ T-cells with NL4.3 with enhanced green fluorescent protein (EGFP) inserted into the nef open reading frame (NL4.3- Δnef-EGFP), there was no EGFP expression detected. These data are consistent with non-productive latent infection of CCL19-treated infected CD4+ T-cells. Treatment of cells with phytohemagluttinin (PHA)/IL-2 or CCL19, prior to infection with WT NL4.3, resulted in a mean fold change in unspliced (US) RNA at day 4 compared to day 0 of 21.2 and 1.1 respectively (p = 0.01; n = 5), and the mean expression of multiply spliced (MS) RNA was 56,000, and 5,000 copies/million cells respectively (p = 0.01; n = 5). In CCL19-treated infected CD4+ T-cells, MS-RNA was detected in the nucleus and not in the cytoplasm; in contrast to PHA/IL-2 activated infected cells where MS RNA was detected in both. Virus could be recovered from CCL19-treated infected CD4+ T-cells following mitogen stimulation (with PHA and phorbyl myristate acetate (PMA)) as well as TNFα, IL-7, prostratin and vorinostat.

Conclusions

In this model of CCL19-induced HIV latency, we demonstrate HIV integration without spontaneous production of infectious virus, detection of MS RNA in the nucleus only, and the induction of virus production with multiple activating stimuli. These data are consistent with ex vivo findings from latently infected CD4+ T-cells from patients on combination antiretroviral therapy, and therefore provide further support of this model as an excellent in vitro model of HIV latency.
Acupuncture as analgesia for low back pain, ankle sprain and migraine in emergency departments: Study protocol for a randomized controlled trial
Authors: Cohen Marc , Parker Shefton , Taylor David , Smit De Villiers , Ben-Meir Michael , Cameron Peter , Xue Charlie
Published: November 2011

Background

Pain is the most common reason that patients present to an emergency department (ED) and is often inadequately managed. Evidence suggests that acupuncture is effective for pain relief, yet it is rarely practiced in the ED. The current study aims to assess the efficacy of acupuncture for providing effective analgesia to patients presenting with acute low back pain, migraine and ankle sprain at the EDs of four hospitals in Melbourne, Australia.

Method

The study is a multi-site, randomized, assessor-blinded, controlled trial of acupuncture analgesia in patients who present to an ED with low back pain, migraine or ankle sprain. Patients will be block randomized to receive either acupuncture alone, acupuncture as an adjunct to pharmacotherapy or pharmacotherapy alone. Acupuncture will be applied according to Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). Pain after one hour, measured using a visual analogue scale (VAS), is the primary outcome. Secondary outcomes measures include the following instruments; the Oswestry low back pain disability questionnaire, 24-hour Migraine Quality of Life questionnaire and Patient's Global Assessment of Ankle Injury Scale. These measures will be recorded at baseline, 1 hour after intervention, each hour until discharge and 48 ± 12 hours of ED discharge. Data will also be collected on the safety and acceptability of acupuncture and health resource utilization.

Discussion

The results of this study will determine if acupuncture, alone or as an adjunct to pharmacotherapy provides effective, safe and acceptable pain relief for patients presenting to EDs with acute back pain, migraine or ankle sprain. The results will also identify the impact that acupuncture treatment may have upon health resource utilisation in the ED setting.

Trial registration

Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12609000989246
Transmission and genetic diversity of Enterococcus faecalis among layer chickens during hatch
Authors: Fertner Mette E , Olsen Rikke H , Bisgaard Magne , Christensen Henrik
Published: November 2011

Background

Studies on transmission of Enterococcus faecalis among chickens during hatch have not been carried out so far. Information about vertical transmission and subsequent spreading and colonization of the cloacal mucosa through cloacal 'drinking' during hatch are important to understand the epidemiology of E. faecalis infections. In the present investigation vertical transmission and subsequent spreading and colonization of the cloacal mucosa of chickens by E. faecalis through cloacal 'drinking' were examined.

Methods

Two different batches of layer chickens originating from 45 weeks old Brown and White Lohmann parents, respectively from the same farm were sampled in the hatcher. Isolates were confirmed to be E. faecalis by polymerase chain reaction (PCR) and further by multilocus sequence typing (MLST) to state their population structure and comparison made to sequence types previously obtained from chicken.

Results

A total of 480 chickens were swabbed from the cloacae just after hatch and after 24 hours. A total of 101 isolates were confirmed as E. faecalis by a species specific PCR. The prevalence of E. faecalis increased from 14% at 0 h to 97% after 24 h for the Brown Lohmann chickens and from 0.5% to 23% for the White Lohmann flock. The 84 isolates analysed by MLST were distributed on 14 sequence types (ST). Three ST (401, 82 and 249) accounted for 64% of all isolates analysed by MLST after 24 h. ST 82 has previously been reported from amyloid arthropathy and other lesions in poultry.

Conclusions

The present findings demonstrated a high potential of a few contaminated eggs or embryos to rapidly facilitate the spread of E. faecalis to almost all chickens during hatch.
Functional characterization and target discovery of glycoside hydrolases from the digestome of the lower termite Coptotermes gestroi
Authors: Franco Cairo João Paulo L , Leonardo Flávia C , Alvarez Thabata M , Ribeiro Daniela A , Büchli Fernanda , Costa-Leonardo Ana M , Carazzolle Marcelo F , Costa Fernando F , Paes Leme Adriana F , Pereira Gonçalo AG , Squina Fabio M
Published: November 2011

Background

Lignocellulosic materials have been moved towards the forefront of the biofuel industry as a sustainable resource. However, saccharification and the production of bioproducts derived from plant cell wall biomass are complex and lengthy processes. The understanding of termite gut biology and feeding strategies may improve the current state of biomass conversion technology and bioproduct production.

Results

The study herein shows comprehensive functional characterization of crude body extracts fromCoptotermes gestroialong with global proteomic analysis of the termite's digestome, targeting the identification of glycoside hydrolases and accessory proteins responsible for plant biomass conversion. The crude protein extract fromC. gestroiwas enzymatically efficient over a broad pH range on a series of natural polysaccharides, formed by glucose-, xylose-, mannan- and/or arabinose-containing polymers, linked by various types of glycosidic bonds, as well as ramification types. Our proteomic approach successfully identified a large number of relevant polypeptides in theC. gestroidigestome. A total of 55 different proteins were identified and classified into 29 CAZy families. Based on the total number of peptides identified, the majority of components found in theC. gestroidigestome were cellulose-degrading enzymes. Xylanolytic enzymes, mannan- hydrolytic enzymes, pectinases and starch-degrading and debranching enzymes were also identified. Our strategy enabled validation of liquid chromatography with tandem mass spectrometry recognized proteins, by enzymatic functional assays and by following the degradation products of specific 8-amino-1,3,6-pyrenetrisulfonic acid labeled oligosaccharides through capillary zone electrophoresis.

Conclusions

Here we describe the first global study on the enzymatic repertoire involved in plant polysaccharide degradation by the lower termiteC. gestroi. The biochemical characterization of whole body termite extracts evidenced their ability to cleave all types of glycosidic bonds present in plant polysaccharides. The comprehensive proteomic analysis, revealed a complete collection of hydrolytic enzymes including cellulases (GH1, GH3, GH5, GH7, GH9 and CBM 6), hemicellulases (GH2, GH10, GH11, GH16, GH43 and CBM 27) and pectinases (GH28 and GH29).
It is time to consider third‐line options in antiretroviral‐experienced paediatric patients?
Authors: van Zyl Gert U , Rabie Helena , Nuttall James J , Cotton Mark F
Published: November 2011

Background

The historic use of full‐dose ritonavir as part of an unboosted protease inhibitor (PI)‐based antiretroviral therapy regimen in some South African children contributes to the frequent accumulation of major PI resistance mutations.

Methods

In order to describe the prevalence of major PI resistance in children failing antiretroviral therapy and to investigate the clinical, immunological and virological outcomes in children with PI resistance, we conducted a cross‐sectional study, with a nested case series, following up those children with major PI resistance. The setting was public health sector antiretroviral clinics in the Western Cape province of South Africa, and the subjects were children failing antiretroviral therapy. The following outcome measures were investigated: CD4 count, viral load and resistance mutations.

Results

Fourteen (17%) of 82 patients, referred from tertiary hospitals, had major PI resistance. All these patients were exposed to regimens that included ritonavir as a single PI. Immune reconstitution and clinical benefit were achieved when using a lopinavir/ritonavir‐based treatment regimen in these children with prior PI resistance. At first HIV‐1 viral load follow up after initial resistance testing (n = 11), only one patient had a viral load of less than 400 copies/ml; at a subsequent follow up (n = 9), the viral loads of five patients were less than 400 copies/ml. Patients retained on LPV/r had lower viral loads than those switched to a non‐nucleoside reverse transcriptase inhibitor (NNRTI). However, two of three patients with follow‐up resistance tests accumulated additional PI resistance.

Conclusions

In children with pre‐existing PI resistance, although initially effective, the long‐term durability of a lopinavir/ritonavir‐based treatment regimen can be compromised by the accumulation of resistance mutations. Furthermore, a second‐line NNRTI regimen is often not durable in these patients. As genotypic resistance testing and third‐line treatment regimens are costly and limited in availability, we propose eligibility criteria to identify patients with high risk for resistance and guidance on drug selection for children who would benefit from third‐line therapy.
Characterization and potential functional significance of human-chimpanzee large INDEL variation
Authors: Polavarapu Nalini , Arora Gaurav , Mittal Vinay K , McDonald John F
Published: November 2011

Background

Although humans and chimpanzees have accumulated significant differences in a number of phenotypic traits since diverging from a common ancestor about six million years ago, their genomes are more than 98.5% identical at protein-coding loci. This modest degree of nucleotide divergence is not sufficient to explain the extensive phenotypic differences between the two species. It has been hypothesized that the genetic basis of the phenotypic differences lies at the level of gene regulation and is associated with the extensive insertion and deletion (INDEL) variation between the two species. To test the hypothesis that large INDELs (80 to 12,000 bp) may have contributed significantly to differences in gene regulation between the two species, we categorized human-chimpanzee INDEL variation mapping in or around genes and determined whether this variation is significantly correlated with previously determined differences in gene expression.

Results

Extensive, large INDEL variation exists between the human and chimpanzee genomes. This variation is primarily attributable to retrotransposon insertions within the human lineage. There is a significant correlation between differences in gene expression and large human-chimpanzee INDEL variation mapping in genes or in proximity to them.

Conclusions

The results presented herein are consistent with the hypothesis that large INDELs, particularly those associated with retrotransposons, have played a significant role in human-chimpanzee regulatory evolution.
Reduction in hospital-wide mortality after implementation of a rapid response team: a long-term cohort study
Authors: Beitler Jeremy R , Link Nate , Bails Douglas B , Hurdle Kelli , Chong David H
Published: November 2011

Introduction

Rapid response teams (RRTs) have been shown to reduce cardiopulmonary arrests outside the intensive care unit (ICU). Yet the utility of RRTs remains in question, as most large studies have failed to demonstrate a significant reduction in hospital-wide mortality after RRT implementation.

Methods

A cohort design with historical controls was used to determine the effect on hospital-wide mortality of an RRT in which clinical judgment, in addition to vital-signs criteria, was widely promoted as a key trigger for activation. All nonprisoner patients admitted to a tertiary referral public teaching hospital from 2003 through 2008 were included. In total, 77, 021 admissions before RRT implementation (2003 through 2005) and 79, 013 admissions after RRT implementation (2006 through 2008) were evaluated. The a priori primary outcome was unadjusted hospital-wide mortality. A Poisson regression model was then used to adjust for hospital-wide mortality trends over time. Secondary outcomes defined a priori were unadjusted out-of-ICU mortality and out-of-ICU cardiopulmonary-arrest codes.

Results

In total, 855 inpatient RRTs (10.8 per 1, 000 hospital-wide discharges) were activated during the 3-year postintervention period. Forty-seven percent of RRTs were activated for reasons of clinical judgment. Hospital-wide mortality decreased from 15.50 to 13.74 deaths per 1, 000 discharges after RRT implementation (relative risk, 0.887; 95% confidence interval (CI), 0.817 to 0.963; P = 0.004). After adjusting for inpatient mortality trends over time, the reduction in hospital-wide mortality remained statistically significant (relative risk, 0.825; 95% CI, 0.694 to 0.981; P = 0.029). Out-of-ICU mortality decreased from 7.08 to 4.61 deaths per 1, 000 discharges (relative risk, 0.651; 95% CI, 0.570 to 0.743; P < 0.001). Out-of-ICU cardiopulmonary-arrest codes decreased from 3.28 to 1.62 codes per 1, 000 discharges (relative risk, 0.493; 95% CI, 0.399 to 0.610; P < 0.001).

Conclusions

Implementation of an RRT in which clinical judgment, in addition to vital-signs criteria, was widely cited as a rationale for activation, was associated with a significant reduction in hospital-wide mortality, out-of-ICU mortality, and out-of-ICU cardiopulmonary-arrest codes. The frequent use of clinical judgment as a criterion for RRT activation was associated with high RRT utilization.
Taking Care: Community, Family, and Dying in Place
Authors: Hoverman J. Russell
Published: November 2011

Medicine, and cancer medicine particularly, exists on the interface of the human condition and science. The profession is distinguished by its human side, yet it is science that informs and complements patient interaction.
Perspectives From the Other Side: A Physician and Cancer Survivor
Authors: Stone Susan C.
Published: November 2011

ASCO has made great strides to integrate palliative care into the comprehensive care model. However, much work remains to ensure that all patients, whether receiving curative or palliative therapy, have a good quality of life.
Palliative Care Needs of Patients With Cancer Living in the Community
Authors: Kamal Arif H. , Bull Janet , Kavalieratos Dio , Taylor Donald H. , Downey William , Abernethy Amy P.
Published: November 2011

The authors describe the current palliative care needs of a population of community-dwelling patients with advanced cancer who are not yet ready for transition to hospice.
The Type 1 Insulin-Like Growth Factor Receptor (IGF-IR) Pathway Is Mandatory for the Follistatin-Induced Skeletal Muscle Hypertrophy
Authors: Kalista S. , Schakman O. , Gilson H. , Lause P. , Demeulder B. , Bertrand L. , Pende M. , Thissen J. P.
Published: November 2011

Myostatin inhibition by follistatin (FS) offers a new approach for muscle mass enhancement. The aim of the present study was to characterize the mediators responsible for the FS hypertrophic action on skeletal muscle in male mice. Because IGF-I and IGF-II, two crucial skeletal muscle growth factors, are induced by myostatin inhibition, we assessed their role in FS action. First, we tested whether type 1 IGF receptor (IGF-IR) is required for FS-induced hypertrophy. By using mice expressing a dominant-negative IGF-IR in skeletal muscle, we showed that IGF-IR inhibition blunted by 63% fiber hypertrophy caused by FS. Second, we showed that FS caused the same degree of fiber hypertrophy in wild-type and IGF-II knockout mice. We then tested the role of the signaling molecules stimulated by IGF-IR, in particular the Akt/mammalian target of rapamycin (mTOR)/70-kDa ribosomal protein S6 kinase (S6K) pathway. We investigated whether Akt phosphorylation is required for the FS action. By cotransfecting a dominant-negative form of Akt together with FS, we showed that Akt inhibition reduced by 65% fiber hypertrophy caused by FS. Second, we evaluated the role of mTOR in FS action. Fiber hypertrophy induced by FS was reduced by 36% in rapamycin-treated mice. Finally, because the activity of S6K is increased by FS, we tested its role in FS action. FS caused the same degree of fiber hypertrophy in wild-type and S6K1/2 knockout mice. In conclusion, the IGF-IR/Akt/mTOR pathway plays a critical role in FS-induced muscle hypertrophy. In contrast, induction of IGF-II expression and S6K activity by FS are not required for the hypertrophic action of FS.
The Impact of Delaying the Delay Announcements
Authors: Allon Gad , Bassamboo Achal
Published: November 2011

Many service providers use delay announcements to inform customers of anticipated delays. However, this information is usually not provided immediately but after a short period of time (spent either waiting or occupied by the system). The focus of this paper is on the impact of this postponement on the ability of the firm to influence customer behavior by communicating nonverifiable congestion information to its customers, as well as on the profits and utilities for the firm and the customers, respectively. We show that this postponement can actually help the firm create credibility and augment the resulting equilibrium. However, in other settings this delay can also detract from the resulting equilibrium. Furthermore, we show that whenever credibility is created it improves not only the profit for the firm but also the customers' overall utility under certain settings.
On reconstruction of Lamé coefficients from partial Cauchy data
Authors: Imanuvilov Oleg Yu. , Yamamoto Masahiro
Published: November 2011

For the isotropic Lamé system we prove that if the Lamé coefficient μ is a positive constant, both Lamé coefficients may be recovered from the partial Cauchy data.
Molecular response of polyethylene nanocomposites to high velocity impact: a Raman observation
Authors: Cai Dongyu , Song Mo
Published: November 2011

A Raman observation was carried out to understand the molecular response of polyethylene (PE) to high velocity impact in presence of carbon nanotubes and carbon black, respectively. The high velocity impact was performed in a Split Hopkinson Pressure Bar. The change of molecular vibration detected by a Raman spectroscopy indicated that the phase transition of nanofiller-induced crystallites took place under high velocity impact in the nanocomposites, whereas it was not found in PE. It was believed that the phase transition brought by nanofillers could benefit the energy dissipation of the PE nanocomposites under high velocity impact.
Avoiding Pitfalls in the Recruiting Process
Authors: Simons Sherri Lee
Published: November 2011

AS HISTORY REPEATS ITSELF, the national health care system faces another nursing shortage crisis. Vacant full-time positions in acute care facilities alone number 120,000, a figure projected to continue climbing at an unprecedented rate, with long-term and permanent effects.1 One nursing labor economist, Peter Buerhaus, forecasts that this is only the beginning.2 Some organizations, desperate for help, are recruiting registered nurses from countries as far away as the Republic of the Philippines and Indonesia. Legions of traveling nurses and agency personnel have no difficulty finding work.1 According to one survey, specialty unit positions, such as those in the NICU, had the highest vacancy rates and were the hardest to fill in 57 percent of the hospitals.3
Osteogenesis Imperfecta
Authors: McLean Kathryn
Published: November 2011

Osteogenesis imperfecta (OI) is a rare congenital disorder of collagen production that results in brittle bones and affects other body systems containing collagen. This article reviews the current body of knowledge about OI and the management of infants with the disorder. Relieving pain, reducing the incidence of new fractures, establishing adequate follow-up, and connecting parents with community resources are the goals of management during the neonatal period. A case study illustrates management and the discharge process.
Randomized Controlled Trial of Kangaroo Care: Cardiorespiratory and Thermal Effects on Healthy Preterm Infants
Authors: Ludington-Hoe Susan , Anderson Gene Cranston , Swinth Joan , Thompson Carol , Hadeed Anthony
Published: November 2011

Purpose:To determine the safety and effects on healthy preterm infants of three continuous hours of kangaroo care (KC) compared to standard NICU care by measuring cardiorespiratory and thermal responses.

Design:Randomized controlled trial—pretest-test-posttest control group design.

Sample:Twenty-four healthy preterm infants (33–35 weeks gestation at birth) nearing discharge. Eleven of the infants received KC; 13 received standard NICU care.

Main Outcome Variables:Heart rate, respiratory rate, oxygen saturation, and abdominal skin temperature were manually recorded every minute. Apnea, bradycardia, periodic breathing, and regular breathing were captured continuously on a pneumocardiogram printout. Three consecutive interfeeding intervals (three hours each) on one day constituted the pretest, test, and posttest periods.

Results:Mean cardiorespiratory and temperature outcomes remained within clinically acceptable ranges during KC. Apnea, bradycardia, and periodic breathing were absent during KC. Regular breathing increased for infants receiving KC compared to infants receiving standard NICU care.
Reliability and Validity: Part II
Authors: Davis Deborah Winders
Published: November 2011

IN THE PREVIOUS COLUMN (Reliability and Validity: Part I, Vol. 23, No.1), I discussed issues related to reliability and validity of the overall study design. In Part II, I will discuss reliability and validity as it relates specifically to measurement scales and instruments. A study must have valid and reliable measures in order to be considered a valid and reliable study. However, a study can have valid and reliable measures, but due to design flaws, not be a valid or reliable study. For the remainder of this column, the termsreliabilityandvaliditywill refer to measurement unless otherwise stated.
Vitamin A and Bronchopulmonary Dysplasia: Research, Issues, and Clinical Practice
Authors: Mentro Anne
Published: November 2011

Vitamin A is a crucial antioxidant for preterm infants because it protects the lungs from oxidative damage induced by the administration of supplemental oxygen. Although all preterm infants are born with smaller vitamin A stores than full-term infants, the store of vitamin A in preterm infants at risk for bronchopulmonary dysplasia (BPD) is often especially deficient. Despite the increases in plasma vitamin A concentrations that have been achieved with vitamin A supplementation, only modest improvements in clinical outcomes and incidence of BPD have been noted in this population. This article reviews the research on vitamin A supplementation for preterm infants, as well as the issues and clinical implications associated with this intervention.
The Premie-Neuro: A Clinical Neurologic Examination of Premature Infants
Authors: Daily Donna Kathryn , Ellison Patricia
Published: November 2011

Purpose: To develop a neurologic assessment tool, the Premie-Neuro, for very low birth weight (VLBW) infants.

Instrument Development: Neurologic data were collected during the course of the NICU stay. Factor analysis was utilized to determine the strength of relationships between items and to reduce the initial number of test items.

Sample: An NICU cohort of 86 preterm infants was enrolled. Mean birth weight was 1,165.8 ± 446.7 grams, and mean gestational age at birth was 28.8 ± 3.2 weeks.

Method: Seventy-five neurologic and behavioral characteristics were assessed in week 1 of life and every 2 weeks thereafter until 38 weeks postconceptional age.

Main Outcome Variable: Three factors, the Neurologic Scale, the Movement Scale, and the Responsiveness Scale, described the neurologic examination.

Results: Factor reliability was calculated for internal consistency (Cronbach alpha coefficient) and ranged from .73 to .82. The Premie-Neuro can be utilized with VLBW infants to monitor neurologic development during NICU care.
Use of Sleep Studies in the Neonatal Intensive Care Unit
Authors: Di Fiore Tina
Published: November 2011

Although early hospital discharge of infants can be both cost-effective and better for developmental care and parent- infant bonding, neonatal caregivers need to ensure infant safety. One of the concerns of early discharge is the risk that premature babies may continue to have apnea, bradycardia, and oxygen desaturation after discharge and that these events can be serious enough to increase morbidity and mortality. The discharging provider bears the responsibility of assessing each infant’s risk for persistent apnea and providing the care and monitoring appropriate for his presumed risk level. Presently there is no universally accepted testing method that can accurately predict which infants will experience significant apnea. Neonatal sleep studies are one of the objective methods being evaluated to identify infants at risk for persistent apnea. This article addresses arguments for and against the use of sleep studies to determine the risk of apnea in neonates about to be discharged, types of sleep studies and what they test, and how sleep studies can be useful in determining infant care.