bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic sequence analysis and characterization of Sneathia amnii sp. nov
Authors: Harwich Michael D , Serrano Myrna G , Fettweis Jennifer M , Alves João MP , Reimers Mark A ,   Vaginal Microbiome Consortium (additional members), Buck Gregory A , Jefferson Kimberly K
Published: December 2012

Background

Bacteria of the genus Sneathia are emerging as potential pathogens of the female reproductive tract. Species of Sneathia, which were formerly grouped with Leptotrichia, can be part of the normal microbiota of the genitourinary tracts of men and women, but they are also associated with a variety of clinical conditions including bacterial vaginosis, preeclampsia, preterm labor, spontaneous abortion, post-partum bacteremia and other invasive infections. Sneathia species also exhibit a significant correlation with sexually transmitted diseases and cervical cancer. Because Sneathia species are fastidious and rarely cultured successfully in vitro; and the genomes of members of the genus had until now not been characterized, very little is known about the physiology or the virulence of these organisms.

Results

Here, we describe a novel species, Sneathia amnii sp. nov, which closely resembles bacteria previously designated "Leptotrichia amnionii". As part of the Vaginal Human Microbiome Project at VCU, a vaginal isolate of S. amnii sp. nov. was identified, successfully cultured and bacteriologically cloned. The biochemical characteristics and virulence properties of the organism were examined in vitro, and the genome of the organism was sequenced, annotated and analyzed. The analysis revealed a reduced circular genome of ~1.34 Mbp, containing ~1,282 protein-coding genes. Metabolic reconstruction of the bacterium reflected its biochemical phenotype, and several genes potentially associated with pathogenicity were identified.

Conclusions

Bacteria with complex growth requirements frequently remain poorly characterized and, as a consequence, their roles in health and disease are unclear. Elucidation of the physiology and identification of genes putatively involved in the metabolism and virulence of S. amnii may lead to a better understanding of the role of this potential pathogen in bacterial vaginosis, preterm birth, and other issues associated with vaginal and reproductive health.
Risk factors and clinical phenotypes of Beijing genotype strains in tuberculosis patients in China
Authors: Pang Yu , Song Yuanyuan , Xia Hui , Zhou Yang , Zhao Bing , Zhao Yanlin
Published: December 2012

Background

Beijing genotype strains are the most predominant strains in China. The aim of this study was to explore risk factors and clinical phenotypes associated with infection with Beijing genotype strains among tuberculosis patients in China.

Methods

Using data and strains derived from the first Chinese national drug resistance base-line survey, we performed a statistical analysis of the relationship between different genotypes, demographic characteristics and clinical phenotypes.

Result

Of patients infected with the 3634 strains for which detailed information was available, we found that people in young age groups [aged under 25 years, OR (95% CI): 1.30(1.03-1.62)], urban people [OR (95% CI): 1.18 (0.47-0.94)], or of Hui ethnicity [OR (95% CI): 1.96 (1.10-3.50)] or those needing retreatment [OR (95% CI): 1.22 (1.03-1.43)] were more likely to be infected with Beijing genotype strains compared with patients who were rural, or of Han ethnicity or those with new TB cases. In contrast, Uyghur [OR (95% CI): 0.45 (0.30-0.67)], or Zhuang ethnicities [OR (95% CI): 0.30 (0.19-0.48)], presented lower than average risk in infections with the Beijing genotype strain. In addition, a higher proportion of patients with hemoptysis [OR (95% CI): 0.81 (0.69-0.94)] and chest pain [OR (95% CI): 0.79 (0.69-0.91)] were infected with non-Beijing genotype strains than with Beijing genotype strains.

Conclusions

In China, young age group, urban people, Hui ethnicity and the earlier treated patients are all high risk factors for infection with Beijing genotype strains, while Uyghur and Zhuang ethnicity are lower than average risk factors for infection. The high rate of chest symptoms occurring in non-Beijing genotype infected patients indicates that more attention should be paid to basic research on non-Beijing genotype strains.
Severe falciparum malaria with dengue coinfection complicated by rhabdomyolysis and acute kidney injury: an unusual case with myoglobinemia, myoglobinuria but normal serum creatine kinase
Authors: Yong Kok Pin , Tan Ban Hock , Low Chian Yong
Published: December 2012

Background

Acute kidney injury (AKI) is a complication of severe malaria, and rhabdomyolysis with myoglobinuria is an uncommon cause. We report an unusual case of severe falciparum malaria with dengue coinfection complicated by AKI due to myoglobinemia and myoglobinuria while maintaining a normal creatine kinase (CK).

Case presentation

A 49-year old Indonesian man presented with fever, chills, and rigors with generalized myalgia and was diagnosed with falciparum malaria based on a positive blood smear. This was complicated by rhabdomyolysis with raised serum and urine myoglobin but normal CK. Despite rapid clearance of the parasitemia with intravenous artesunate and aggressive hydration maintaining good urine output, his myoglobinuria and acidosis worsened, progressing to uremia requiring renal replacement therapy. High-flux hemodiafiltration effectively cleared his serum and urine myoglobin with recovery of renal function. Further evaluation revealed evidence of dengue coinfection and past infection with murine typhus.

Conclusion

In patients with severe falciparum malaria, the absence of raised CK alone does not exclude a diagnosis of rhabdomyolysis. Raised serum and urine myoglobin levels could lead to AKI and should be monitored. In the event of myoglobin-induced AKI requiring dialysis, clinicians may consider using high-flux hemodiafiltration instead of conventional hemodialysis for more effective myoglobin removal. In Southeast Asia, potential endemic coinfections that can also cause or worsen rhabdomyolysis, such as dengue, rickettsiosis and leptospirosis, should be considered.
Up-regulated expression of l-caldesmon associated with malignancy of colorectal cancer
Authors: Kim Kyung-Hee , Yeo Seung-Gu , Kim Won Ki , Kim Dae Yong , Yeo Hyun Yang , Hong Jun Pyu , Chang Hee Jin , Park Ji Won , Kim Sun Young , Kim Byung Chang , Yoo Byong Chul
Published: December 2012

Background

Caldesmon (CaD), a major actin-associated protein, is found in smooth muscle and non-muscle cells. Smooth muscle caldesmon, h-CaD, is a multifunctional protein, and non-muscle cell caldesmon, l-CaD, plays a role in cytoskeletal architecture and dynamics. h-CaD is thought to be an useful marker for smooth muscle tumors, but the role(s) of l-CaD has not been examined in tumors.

Methods

Primary colon cancer and liver metastasis tissues were obtained from colon cancer patients. Prior to chemoradiotherapy (CRT), normal and cancerous tissues were obtained from rectal cancer patients. Whole-tissue protein extracts were analyzed by 2-DE-based proteomics. Expression and phosphorylation level of main cellular signaling proteins were determined by western blot analysis. Cell proliferation after CaD siRNA transfection was monitored by MTT assay.

Results

The expression level of l-CaD was significantly increased in primary colon cancer and liver metastasis tissues compared to the level in the corresponding normal tissues. In cancerous tissues obtained from the patients showing poor response to CRT (Dworak grade 4), the expression of l-CaD was increased compared to that of good response group (Dworak grade 1). In line with, l-CaD positive human colon cancer cell lines were more resistant to 5-fluorouracil (5-FU) and radiation treatment compared to l-CaD negative cell lines. Artificial suppression of l-CaD increased susceptibility of colon cancer cells to 5-FU, and caused an increase of p21 and c-PARP, and a decrease of NF-kB and p-mTOR expression.

Conclusion

Up-regulated expression of l-CaD may have a role for increasing metastatic property and decreasing CRT susceptibility in colorectal cancer cells.
Epidermal growth factor receptor (EGFR) mutations and expression in squamous cell carcinoma of the esophagus in central Asia
Authors: Abedi-Ardekani Behnoush , Dar Nazir Ahmad , Mir Mohammad Muzaffar , Zargar Showkat Ahmad , Lone M Muqbool , Martel-Planche Ghyslaine , Villar Stéphanie , Mounawar Mounia , Saidi Farrokh , Malekzadeh Reza , Hainaut Pierre
Published: December 2012

Background

Esophageal squamous cell carcinoma (ESCC) shows geographic variations in incidence, with high incidences (>50/105 person-years) in central Asia, including North Eastern Iran (Golestan) and Northern India (Kashmir). In contrast to Western countries, smoking does not appear to be a significant risk factor for ESCC in central Asia. In lung adenocarcinoma, activating mutations in the gene encoding epidermal growth factor receptor (EGFR) are frequent in tumors of never smokers of Asian origin, predicting therapeutic sensitivity to Egfr-targeting drugs.

Methods

In this study 152 cases of histologically confirmed ESCC from Iran (Tehran and Golestan Province) and North India (Kashmir Valley) have been analyzed for EGFR mutation by direct sequencing of exons 18–21. Egfr protein expression was evaluated by immunohistochemistry in 34 samples from Tehran and HER2 mutations were analyzed in 54 cases from Kashmir.

Results

A total of 14 (9.2%) EGFR variations were detected, including seven variations in exons. Among those, four (2.6%) were already documented in lung cancers, two were reported as polymorphisms and one was a potentially new activating mutation. All but one variation in introns were previously identified as polymorphisms. Over-expression of Egfr was detected in 22/34 (65%) of tested cases whereas no HER2 mutation was found in 54 cases from Kashmir.

Conclusion

Overall, EGFR mutations appear to be a rare event in ESCC in high incidence areas of central Asia, although a very small proportion of cases may harbor mutations predicting sensitivity to anti-Egfr drugs.
Unique immunologic patterns in fibromyalgia
Authors: Behm Frederick G , Gavin Igor M , Karpenko Oleksiy , Lindgren Valerie , Gaitonde Sujata , Gashkoff Peter A , Gillis Bruce S
Published: December 2012

Background

Fibromyalgia (FM) is a clinical syndrome characterized by chronic pain and allodynia. The diagnosis of FM has been one of exclusion as a test to confirm the diagnosis is lacking. Recent data highlight the role of the immune system in FM. Aberrant expressions of immune mediators, such as cytokines, have been linked to the pathogenesis and traits of FM. We therefore determined whether cytokine production by immune cells is altered in FM patients by comparing the cellular responses to mitogenic activators of stimulated blood mononuclear cells of a large number of patients with FM to those of healthy matched individuals.

Methods

Plasma and peripheral blood mononuclear cells (PBMC) were collected from 110 patients with the clinical diagnosis of FM and 91 healthy donors. Parallel samples of PBMC were cultured overnight in medium alone or in the presence of mitogenic activators; PHA or PMA in combination with ionomycin. The cytokine concentrations of IFN-γ, IL-5, IL-6, IL-8, IL-10, MIP-1β , MCP-1, and MIP1-α in plasma as well as in cultured supernatants were determined using a multiplex immunoassay using bead array technology.

Results

Cytokine levels of stimulated PBMC cultures of healthy control subjects were significantly increased as compared to matched non-stimulated PBMC cultures. In contrast, the concentrations of most cytokines were lower in stimulated samples from patients with FM compared to controls. The decreases of cytokine concentrations in patients samples ranged from 1.5-fold for MIP-1β to 10.2-fold for IL-6 in PHA challenges. In PMA challenges, we observed 1.8 to 4-fold decreases in the concentrations of cytokines in patient samples.

Conclusion

The cytokine responses to mitogenic activators of PBMC isolated from patients with FM were significantly lower than those of healthy individuals, implying that cell-mediated immunity is impaired in FM patients. This novel cytokine assay reveals unique and valuable immunologic traits, which, when combined with clinical patterns, can offer a diagnostic methodology in FM.
Interferon-γ-induced activation of Signal Transducer and Activator of Transcription 1 (STAT1) up-regulates the tumor suppressing microRNA-29 family in melanoma cells
Authors: Schmitt Martina J , Philippidou Demetra , Reinsbach Susanne E , Margue Christiane , Wienecke-Baldacchino Anke , Nashan Dorothee , Behrmann Iris , Kreis Stephanie
Published: December 2012

Background

The type-II-cytokine IFN-γ is a pivotal player in innate immune responses but also assumes functions in controlling tumor cell growth by orchestrating cellular responses against neoplastic cells. The role of IFN-γ in melanoma is not fully understood: it is a well-known growth inhibitor of melanoma cells in vitro. On the other hand, IFN-γ may also facilitate melanoma progression. While interferon-regulated genes encoding proteins have been intensively studied since decades, the contribution of miRNAs to effects mediated by interferons is an emerging area of research.

We recently described a distinct and dynamic regulation of a whole panel of microRNAs (miRNAs) after IFN-γ-stimulation. The aim of this study was to analyze the transcriptional regulation of miR-29 family members in detail, identify potential interesting target genes and thus further elucidate a potential signaling pathway IFN-γ → Jak→ P-STAT1 → miR-29 → miR-29 target genes and its implication for melanoma growth.

Results

Here we show that IFN-γ induces STAT1-dependently a profound up-regulation of the miR-29 primary cluster pri-29a~b-1 in melanoma cell lines. Furthermore, expression levels of pri-29a~b-1 and mature miR-29a and miR-29b were elevated while the pri-29b-2~c cluster was almost undetectable. We observed an inverse correlation between miR-29a/b expression and the proliferation rate of various melanoma cell lines. This finding could be corroborated in cells transfected with either miR-29 mimics or inhibitors. The IFN-γ-induced G1-arrest of melanoma cells involves down-regulation of CDK6, which we proved to be a direct target of miR-29 in these cells. Compared to nevi and normal skin, and metastatic melanoma samples, miR-29a and miR-29b levels were found strikingly elevated in certain patient samples derived from primary melanoma.

Conclusions

Our findings reveal that the miR-29a/b1 cluster is to be included in the group of IFN- and STAT-regulated genes. The up-regulated miR-29 family members may act as effectors of cytokine signalling in melanoma and other cancer cells as well as in the immune system.
Do major life events influence physical activity among older adults: the Longitudinal Aging Study Amsterdam
Authors: Koeneman Margot A , Chinapaw Mai JM , Verheijden Marieke W , van Tilburg Theo G , Visser Marjolein , Deeg Dorly JH , Hopman-Rock Marijke
Published: December 2012

Background

Major life events are associated with a change in daily routine and could thus also affect habitual levels of physical activity. Major life events remain largely unexplored as determinants of older adults’ participation in physical activity and sports. This study focused on two major life events, widowhood and retirement, and asked whether these major life events were associated with moderate to vigorous physical activity (MVPA) and sports participation.

Methods

Data from the first (1992–93) and second (1995–96) wave of the Longitudinal Aging Study Amsterdam (LASA), a prospective cohort study among Dutch adults aged 55 and older, were used. Change in marital status and employment status between baseline and follow-up was assessed by self-report. Time spent in MVPA (min/d) and sports participation (yes/no) was calculated based on the LASA Physical Activity Questionnaire. The association of retirement and widowhood with MVPA and sports participation was assessed in separate multivariate linear and logistic regression analyses, respectively.

Results

Widowhood - N=136 versus 1324 stable married- was not associated with MVPA (B= 3.5 [95%CI:-57.9;64.9]) or sports participation (OR= 0.8 [95%CI:0.5;1.3]). Retired participants (N= 65) significantly increased their time spent in MVPA (B= 32.5 [95%CI:17.8;47.1]) compared to participants who continued to be employed (N= 121), but not their sports participation. Age was a significant effect modifier (B= 7.5 [90%CI:-1.1;13.8]), indicating a greater increase in MVPA in older retirees.

Discussion

Our results suggest that the associations found varied by the two major life events under investigation. MVPA increased after retirement, but no association with widowhood was seen.
Self-assembled silver nanoislands formed on glass surface via out-diffusion for multiple usages in SERS applications
Authors: Zhurikhina Valentina V , Brunkov Pavel N , Melehin Vladimir G , Kaplas Tommi , Svirko Yuri , Rutckaia Victoria V , Lipovskii Andrey A
Published: December 2012

We demonstrate that silver nanoisland film self-assembled on the surface of silver-containing glass in the course of thermal processing in hydrogen is capable to detect 10−7 M concentration of rhodamine 6G in water using surface enhanced Raman spectroscopy (SERS) technique. The film can be multiply restored on the same glass substrate via annealing of the glass in hydrogen. We showed that the film can be self-assembled after as much as ten circles of the substrate cleaning followed by annealing. The proposed technique of the silver nanoisland film formation enables multiple usage of the same glass substrate in SERS experiments.
Optical properties of hybrid T3Pyr/SiO2/3C-SiC nanowires
Authors: Fabbri Filippo , Rossi Francesca , Melucci Manuela , Manet Ilse , Attolini Giovanni , Favaretto Laura , Zambianchi Massimo , Salviati Giancarlo
Published: December 2012

A new class of nanostructured hybrid materials is developed by direct grafting of a model thiophene-based organic dye on the surface of 3C-SiC/SiO2 core/shell nanowires. TEM-EDX analysis reveals that the carbon distribution is more spread than it would be, considering only the SiC core size, suggesting a main contribution from C of the oligothiophene framework. Further, the sulfur signal found along the treated wires is not detected in the as-grown samples. In addition, the fluorescent spectra are similar for the functionalized nanostructures and T3Pyr in solution, confirming homogeneous molecule grafting on the nanowire surface. Chemical and luminescence characterizations confirm a homogeneous functionalization of the nanowires. In particular, the fluorophore retains its optical properties after functionalization.
Cycling and bone health: a systematic review
Authors: Olmedillas Hugo , González-Agüero Alejandro , Moreno Luis A , Casajus José A , Vicente-Rodríguez Germán
Published: December 2012

Background

Cycling is considered to be a highly beneficial sport for significantly enhancing cardiovascular fitness in individuals, yet studies show little or no corresponding improvements in bone mass.

Methods

A scientific literature search on studies discussing bone mass and bone metabolism in cyclists was performed to collect all relevant published material up to April 2012. Descriptive, cross-sectional, longitudinal and interventional studies were all reviewed. Inclusion criteria were met by 31 studies.

Results

Heterogeneous studies in terms of gender, age, data source, group of comparison, cycling level or modality practiced among others factors showed minor but important differences in results. Despite some controversial results, it has been observed that adult road cyclists participating in regular training have low bone mineral density in key regions (for example, lumbar spine). Conversely, other types of cycling (such as mountain biking), or combination with other sports could reduce this unsafe effect. These results cannot yet be explained by differences in dietary patterns or endocrine factors.

Conclusions

From our comprehensive survey of the current available literature it can be concluded that road cycling does not appear to confer any significant osteogenic benefit. The cause of this may be related to spending long hours in a weight-supported position on the bike in combination with the necessary enforced recovery time that involves a large amount of time sitting or lying supine, especially at the competitive level.
Biologic activity of the novel small molecule STAT3 inhibitor LLL12 against canine osteosarcoma cell lines
Authors: Couto Jason I , Bear Misty D , Lin Jiayuh , Pennel Michael , Kulp Samuel K , Kisseberth William C , London Cheryl A
Published: December 2012

Background

STAT3 [1] has been shown to be dysregulated in nearly every major cancer, including osteosarcoma (OS). Constitutive activation of STAT3, via aberrant phosphorylation, leads to proliferation, cell survival and resistance to apoptosis. The present study sought to characterize the biologic activity of a novel allosteric STAT3 inhibitor, LLL12, in canine OS cell lines.

Results

We evaluated the effects of LLL12 treatment on 4 canine OS cell lines and found that LLL12 inhibited proliferation, induced apoptosis, reduced STAT3 phosphorylation, and decreased the expression of several transcriptional targets of STAT3 in these cells. Lastly, LLL12 exhibited synergistic anti-proliferative activity with the chemotherapeutic doxorubicin in the OS lines.

Conclusion

LLL12 exhibits biologic activity against canine OS cell lines through inhibition of STAT3 related cellular functions supporting its potential use as a novel therapy for OS.
KL-6, a Human MUC1 Mucin, as a prognostic marker for diffuse alveolar hemorrhage syndrome
Authors: Kida Yoshiko , Ohshimo Shinichiro , Ota Kohei , Tamura Tomoko , Otani Tadatsugu , Une Kazunobu , Sadamori Takuma , Iwasaki Yasumasa , Bonella Francesco , Hattori Noboru , Hirohashi Nobuyuki , Guzman Josune , Costabel Ulrich , Kohno Nobuoki , Tanigawa Koichi
Published: December 2012

Background

Diffuse alveolar hemorrhage syndrome is a life threatening condition with diverse etiologies. Sensitive prognostic markers for diffuse alveolar hemorrhage have not been well investigated. Serum KL-6 is a biomarker for various interstitial lung disease associated with disease activity and prognosis. The purpose of the present study was to evaluate the clinical utility of serum KL-6 level as a prognostic marker for diffuse alveolar hemorrhage.

Methods

We retrospectively collected 41 consecutive patients clinically diagnosed as having diffuse alveolar hemorrhage who were admitted to the Intensive Care Unit of Hiroshima University Hospital between 2004 and 2011. Correlation between prognosis and age, sex, laboratory findings including serum KL-6, radiological findings, ventilatory modes or therapeutic regimens were evaluated.

Results

Baseline and peak serum KL-6 levels were significantly higher in non-survivors compared with survivors. An increase in KL-6 levels during the initial week was associated with a subsequent deterioration of the oxygenation index. Higher baseline KL-6 levels and higher peak KL-6 levels were strongly correlated with death. With a cut-off level of 700 U/mL for peak KL-6, the sensitivity, specificity and accuracy for non-survival were 75%, 85% and 78%, respectively. In the multivariate analysis, only the peak KL-6 level ≥700 U/ml was an independent poor prognostic factor for diffuse alveolar hemorrhage.

Conclusions

Peak serum KL-6 level ≥700 U/ml may become a clinically useful marker of poor prognosis for diffuse alveolar hemorrhage.
Mathematical modeling of left ventricular dimensional changes in mice during aging
Authors: Yang Tianyi , Chiao Ying Ann , Wang Yunji , Voorhees Andrew , Han Hai-Chao , Lindsey Merry L , Jin Yu-Fang
Published: December 2012

Cardiac aging is characterized by diastolic dysfunction of the left ventricle (LV), which is due in part to increased LV wall stiffness. In the diastolic phase, myocytes are relaxed and extracellular matrix (ECM) is a critical determinant to the changes of LV wall stiffness. To evaluate the effects of ECM composition on cardiac aging, we developed a mathematical model to predict LV dimension and wall stiffness changes in aging mice by integrating mechanical laws and our experimental results. We measured LV dimension, wall thickness, LV mass, and collagen content for wild type (WT) C57/BL6J mice of ages ranging from 7.3 months to those of 34.0 months. The model was established using the thick wall theory and stretch-induced tissue growth to an isotropic and homogeneous elastic composite with mixed constituents. The initial conditions of the simulation were set based on the data from the young mice. Matlab simulations of this mathematical model demonstrated that the model captured the major features of LV remodeling with age and closely approximated experimental results. Specifically, the temporal progression of the LV interior and exterior dimensions demonstrated the same trend and order-of-magnitude change as our experimental results. In conclusion, we present here a validated mathematical model of cardiac aging that applies the thick-wall theory and stretch-induced tissue growth to LV remodeling with age.
Genetic studies of complex human diseases: Characterizing SNP-disease associations using Bayesian networks
Authors: Han Bing , Chen Xue-wen , Talebizadeh Zohreh , Xu Hua
Published: December 2012

Background

Detecting epistatic interactions plays a significant role in improving pathogenesis, prevention, diagnosis, and treatment of complex human diseases. Applying machine learning or statistical methods to epistatic interaction detection will encounter some common problems, e.g., very limited number of samples, an extremely high search space, a large number of false positives, and ways to measure the association between disease markers and the phenotype.

Results

To address the problems of computational methods in epistatic interaction detection, we propose a score-based Bayesian network structure learning method, EpiBN, to detect epistatic interactions. We apply the proposed method to both simulated datasets and three real disease datasets. Experimental results on simulation data show that our method outperforms some other commonly-used methods in terms of power and sample-efficiency, and is especially suitable for detecting epistatic interactions with weak or no marginal effects. Furthermore, our method is scalable to real disease data.

Conclusions

We propose a Bayesian network-based method, EpiBN, to detect epistatic interactions. In EpiBN, we develop a new scoring function, which can reflect higher-order epistatic interactions by estimating the model complexity from data, and apply a fast Branch-and-Bound algorithm to learn the structure of a two-layer Bayesian network containing only one target node. To make our method scalable to real data, we propose the use of a Markov chain Monte Carlo (MCMC) method to perform the screening process. Applications of the proposed method to some real GWAS (genome-wide association studies) datasets may provide helpful insights into understanding the genetic basis of Age-related Macular Degeneration, late-onset Alzheimer's disease, and autism.
Optimizing hybrid assembly of next-generation sequence data from Enterococcus faecium: a microbe with highly divergent genome
Authors: Wang Yajun , Yu Yao , Pan Bohu , Hao Pei , Li Yixue , Shao Zhifeng , Xu Xiaogang , Li Xuan
Published: December 2012

Background

Sequencing of bacterial genomes became an essential approach to study pathogen virulence and the phylogenetic relationship among close related strains. Bacterium Enterococcus faecium emerged as an important nosocomial pathogen that were often associated with resistance to common antibiotics in hospitals. With highly divergent gene contents, it presented a challenge to the next generation sequencing (NGS) technologies featuring high-throughput and shorter read-length. This study was designed to investigate the properties and systematic biases of NGS technologies and evaluate critical parameters influencing the outcomes of hybrid assemblies using combinations of NGS data.

Results

A hospital strain of E. faecium was sequenced using three different NGS platforms: 454 GS-FLX, Illumina GAIIx, and ABI SOLiD4.0, to approximately 28-, 500-, and 400-fold coverage depth. We built a pipeline that merged contigs from each NGS data into hybrid assemblies. The results revealed that each single NGS assembly had a ceiling in continuity that could not be overcome by simply increasing data coverage depth. Each NGS technology displayed some intrinsic properties, i.e. base calling error, systematic bias, etc. The gaps and low coverage regions of each NGS assembly were associated with lower GC contents. In order to optimize the hybrid assembly approach, we tested with varying amount and different combination of NGS data, and obtained optimal conditions for assembly continuity. We also, for the first time, showed that SOLiD data could help make much improved assemblies of E. faecium genome using the hybrid approach when combined with other type of NGS data.

Conclusions

The current study addressed the difficult issue of how to most effectively construct a complete microbial genome using today's state of the art sequencing technologies. We characterized the sequence data and genome assembly from each NGS technologies, tested conditions for hybrid assembly with combinations of NGS data, and obtained optimized parameters for achieving most cost-efficiency assembly. Our study helped form some guidelines to direct genomic work on other microorganisms, thus have important practical implications.
Induction of cytokines in different organs after intranasal inoculation of Campylobacter jejuni in mice
Authors: Al-Banna Nadia A , Raghupathy Raj , Albert M John
Published: December 2012

Background

Cytokine production and histopathological changes occur in the lungs of mice after intranasal inoculation with Campylobacter jejuni, but the levels of cytokines in different organs to which C. jejuni disseminates have not been studied.

Findings

Adult BALB/c mice were intranasally inoculated with C. jejuni 81– 176 (test) or phosphate-buffered saline (control) (n=16 per group). The levels of cytokines in the organs (spleen, liver, and small and large intestines) to which C. jejuni disseminated were measured by ELISA. Two cytokine patterns were observed. First, increased proinflammatory cytokines, TNF-α, IL-1, and IL-2, were followed by anti-inflammatory cytokines, IL-4 and IL-10 in the spleen and large intestine. Second, in the liver and small intestine, there was a predominant production of anti-inflammatory cytokines, IL-4 and IL-10, with some increase in IL-2 levels. In the spleen and intestines, the levels of pro- and anti-inflammatory cytokines were concurrently increased.

Conclusion

Dissemination of C. jejuni is associated with the production of different cytokine profiles in different tissues, with the proinflammatory response appearing in the spleen and large intestine at an earlier time point than in the liver and small intestine. The organs produce different cytokine profiles in response to C. jejuni dissemination. These preliminary findings should be confirmed with a study involving a larger group of animals.
Persistent inter‐industry wage differences: rent sharing and opportunity costs
Authors: Abowd John M , Kramarz Francis , Lengermann Paul , McKinney Kevin L , Roux Sébastien
Published: December 2012

We reconsider the potential for explaining inter‐industry wage differences by decomposing those differences into parts due to individual and employer heterogeneity, respectively. Using longitudinally linked employer‐employee data, we estimate the model for the United States and France. The part arising from individual heterogeneity can be theoretically and empirically related to the worker’s opportunity wage rate. The part arising from employer heterogeneity can similarly be related to product market quasi‐rents and relative bargaining power. We find that these two variables are highly correlated with both parts of the differential in France. Although the U.S. inter‐industry wage differentials are strongly correlated with those in France, the decomposition is more nuanced in the American data, where the opportunity wage rate and the product market conditions are related to both the personal and employer heterogeneity.

JEL codes

J31, J50, L10
Optimizing positive end-expiratory pressure by oscillatory mechanics minimizes tidal recruitment and distension: an experimental study in a lavage model of lung injury
Authors: Zannin Emanuela , Dellaca Raffaele L , Kostic Peter , Pompilio Pasquale P , Larsson Anders , Pedotti Antonio , Hedenstierna Goran , Frykholm Peter
Published: December 2012

Introduction

It is well established that during mechanical ventilation of patients with acute respiratory distress syndrome cyclic recruitment/derecruitment and overdistension are potentially injurious for lung tissues. We evaluated whether the forced oscillation technique (FOT) could be used to guide the ventilator settings in order to minimize cyclic lung recruitment/derecruitment and cyclic mechanical stress in an experimental model of acute lung injury.

Methods

We studied six pigs in which lung injury was induced by bronchoalveolar lavage. The animals were ventilated with a tidal volume of 6 ml/kg. Forced oscillations at 5 Hz were superimposed on the ventilation waveform. Pressure and flow were measured at the tip and at the inlet of the endotracheal tube respectively. Respiratory system reactance (Xrs) was computed from the pressure and flow signals and expressed in terms of oscillatory elastance (EX5). Positive end-expiratory pressure (PEEP) was increased from 0 to 24 cm H2O in steps of 4 cm H2O and subsequently decreased from 24 to 0 in steps of 2 cm H2O. At each PEEP step CT scans and EX5 were assessed at end-expiration and end-inspiration.

Results

During deflation the relationship between both end-expiratory and end-inspiratory EX5 and PEEP was a U-shaped curve with minimum values at PEEP = 13.4 ± 1.0 cm H2O (mean ± SD) and 13.0 ± 1.0 cm H2O respectively. EX5 was always higher at end-inspiration than at end-expiration, the difference between the average curves being minimal at 12 cm H2O. At this PEEP level, CT did not show any substantial sign of intra-tidal recruitment/derecruitment or expiratory lung collapse.

Conclusions

Using FOT it was possible to measure EX5 both at end-expiration and at end-inspiration. The optimal PEEP strategy based on end-expiratory EX5 minimized intra-tidal recruitment/derecruitment as assessed by CT, and the concurrent attenuation of intra-tidal variations of EX5 suggests that it may also minimize tidal mechanical stress.
Risk factors for dementia after critical illness in elderly medicare beneficiaries
Authors: Guerra Carmen , Linde-Zwirble Walter T , Wunsch Hannah
Published: December 2012

Introduction

Hospitalization increases the risk of a subsequent diagnosis of dementia. We aimed to identify diagnoses or events during a hospitalization requiring critical care that are associated with a subsequent dementia diagnosis in the elderly.

Methods

A cohort study of a random 5% sample of Medicare beneficiaries who received intensive care in 2005 and survived to hospital discharge, with three years of follow-up (through 2008) was conducted using Medicare claims files. We defined dementia using the International Classification of Diseases, 9th edition, clinical modification (ICD-9-CM) codes and excluded patients with any prior diagnosis of dementia or cognitive impairment in the year prior to admission. We used an extended Cox model to examine the association between diagnoses and events associated with the critical illness and a subsequent diagnosis of dementia, adjusting for known risk factors for dementia.

Results

Over the three years of follow-up, dementia was newly diagnosed in 4,519 (17.8%) of 25,368 patients who received intensive care and survived to hospital discharge. After accounting for known risk factors, having an infection (adjusted hazard ratio (AHR) = 1.25; 95% CI, 1.17 to 1.35), or a diagnosis of severe sepsis (AHR = 1.40; 95% CI, 1.28 to 1.53), acute neurologic dysfunction (AHR = 2.06; 95% CI, 1.72 to 2.46), and acute dialysis (AHR = 1.70; 95% CI, 1.30 to 2.23) were all independently associated with a subsequent diagnosis of dementia. No other measured ICU factors, such as need for mechanical ventilation, were independently associated.

Conclusions

Among ICU events, infection or severe sepsis, neurologic dysfunction, and acute dialysis were independently associated with a subsequent diagnosis of dementia. Patient prognostication, as well as future research into post-ICU cognitive decline, should focus on these higher-risk subgroups.
Brain-derived neurotrophic factor plasma levels are associated with mortality in critically ill patients even in the absence of brain injury
Authors: Ritter Cristiane , Miranda Aline S , Giombelli Vinícius Renê , Tomasi Cristiane D , Comim Clarissa M , Teixeira Antonio Lucio , Quevedo João , Dal-Pizzol Felipe
Published: December 2012

Introduction

Because of its relevance to the functioning of the central nervous system, brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of different neuropsychiatric diseases. Whether the BDNF level can be a marker of brain dysfunction and thus predict mortality in critically ill patients is not known. Thus we aimed to determine whether the plasma levels of BDNF are associated with morbidity and mortality in critically ill patients.

Methods

Healthy volunteers (n = 40) and consecutive patients older than 18 years (n = 76) admitted for more than 24 hours in an Intensive Care Unit (ICU) in a University hospital between July and October 2010 were included in the present study. First blood samples were collected within 12 hours of enrollment (D0), and a second sample, 48 hours after (D2) for determination of plasma BDNF levels. The relation between BDNF levels and mortality was the primary outcome. The secondary outcomes were the relation between BDNF levels and delirium and coma-free days (DCFD) and ICU and hospital length of stay (LOS).

Results

Admission plasma levels of BDNF were higher in ICU patients when compared with healthy volunteers (1,536 (962) versus 6,565 (2,838) pg/ml). The mean BDNF D2 was significantly lower in nonsurvivor patients (5,865 (2,662) versus 6,741 (2,356) pg/ml). After adjusting for covariates, BDNF levels, the need for mechanical ventilation, and sepsis were associated with mortality. Even in patients without clinically detectable brain dysfunction, lower BDNF D2 levels were associated with mortality. BDNF D2 had a mild correlation to DCFD (r = 0.44), but not to ICU and hospital LOS. In addition, plasma BDNF did not correlate to different plasma cytokines and platelets levels.

Conclusions

The plasma levels of BDNF were independently associated with mortality, even in the absence of clinically detectable brain dysfunction.
Natural variation of H3K27me3 distribution between two Arabidopsis accessions and its association with flanking transposable elements
Authors: Dong Xue , Reimer Julia , Göbel Ulrike , Engelhorn Julia , He Fei , Schoof Heiko , Turck Franziska
Published: December 2012

Background

Histone H3 lysine 27 tri-methylation and lysine 9 di-methylation are independent repressive chromatin modifications in Arabidopsis thaliana. H3K27me3 is established and maintained by Polycomb repressive complexes whereas H3K9me2 is catalyzed by SUVH histone methyltransferases. Both modifications can spread to flanking regions after initialization and were shown to be mutually exclusive in Arabidopsis.

Results

We analyzed the extent of natural variation of H3K27me3 in the two accessions Landsberg erecta (Ler) and Columbia (Col) and their F1 hybrids. The majority of H3K27me3 target genes in Col were unchanged in Ler and F1 hybrids. A small number of Ler-specific targets were detected and confirmed. Consistent with a cis-regulatory mechanism for establishing H3K27me3, differential targets showed allele-specific H3K27me3 in hybrids. Five Ler-specific targets showed the active mark H3K4me3 in Col and for this group, differential H3K27me3 enrichment accorded to expression variation. On the other hand, the majority of Ler-specific targets were not expressed in Col, Ler or 17 other accessions. Instead of H3K27me3, the antagonistic mark H3K9me2 and other heterochromatic features were observed at these loci in Col. These loci were frequently flanked by transposable elements, which were often missing in the Ler genome assembly.

Conclusion

There is little variation in H3K27me3 occupancy within the species, although H3K27me3 targets were previously shown as overrepresented among differentially expressed genes. The existing variation in H3K27me3 seems mostly explained by flanking polymorphic transposable elements. These could nucleate heterochromatin, which then spreads into neighboring H3K27me3 genes, thus converting them to H3K9me2 targets.
Inhibitory Roles of Prohibitin and Chemerin in FSH-Induced Rat Granulosa Cell Steroidogenesis
Authors: Wang Qi , Leader Arthur , Tsang Benjamin K.
Published: December 2012

Follicular differentiation is a tightly regulated process involving various endocrine, autocrine, and paracrine factors. The biosynthesis of progesterone and estradiol in response to FSH involves the regulation of multiple steroidogenic enzymes, such as p450 cholesterol side-chain cleavage enzyme and aromatase. Here we demonstrated that prohibitin (PHB), a multifunctional protein, inhibits FSH-induced progesterone and estradiol secretion in rat granulosa cells. The mRNA abundances of cyp11a (coding p450 cholesterol side-chain cleavage enzyme) and cyp19 (coding aromatase) were also suppressed by PHB in a time-dependent manner. It is known that a novel adipokine chemerin suppresses FSH-induced steroidogenesis in granulosa cells. Chemerin up-regulates the content of PHB, and PHB knockdown attenuates the suppressive role of chemerin on steroidogenesis. In addition, inhibition of phosphatidylinositol 3-kinase/Akt pathway enhances the suppressive action of PHB, whereas expression of constitutively active Akt attenuates this response. These findings suggest that PHB is a novel negative regulator of FSH-induced steroidogenesis, and its action with chemerin may contribute to the dysregulation of steroidogenesis in the pathogenesis of polycystic ovarian syndrome.
Telling Histories: A Conversation with Laurent Dubois and Greg Grandin
Authors: Wilder Gary
Published: December 2012

When an earthquake devastated the area around the Haitian capital city in January 2010, Laurent Dubois, a historian of Haiti working in the United States, was struck by the extent of the general ignorance about Haiti in the United States, and at the same time, at least for some, the curiosity to learn more about it. Inspired by his conversations with colleagues, journalists, and the general public, he authored a scholarly book that examined Haiti's understudied nineteenth century. Greg Grandin, a historian of Latin America, has likewise spent his career both overturning received truths about the region's history and present-day politics and confronting an often dangerously misinformed public as well as his academic peers. In this discussion with Gary Wilder held at a public forum in 2012, Dubois and Grandin, both scholars who have taken an especially active part in debates both in and outside academia, discuss their work and reflect on the importance as well as the challenges of practicing politically engaged history in light of the distorted views of the past that many in the United States share about Latin America and the Caribbean.
Transnational Hispaniola: Toward New Paradigms in Haitian and Dominican Studies
Authors: Mayes April , Martín Yolanda C. , Decena Carlos Ulises , Jayaram Kiran , Alexis Yveline
Published: December 2012

In this piece by a collective of scholars, activists, and artists, the authors clarify what they mean by “Transnational Hispaniola” and why they believe this conceptualization of the island complements the work done by social movements combating sexism, racism, and homophobia. They assess the responses to their efforts so far — by people in the Dominican Republic and in the United States — to reflect critically upon the promises and limitations of this work. They end by explaining their goals for the future challenges as they plan a third (but hopefully not final) conference, this time in Haiti.
History after the Earthquake: Shifting the Axis of Teaching
Authors: Doubleday Simon R.
Published: December 2012

This article reflects on the experience of teaching an online summer course that focused on rethinking history, in the aftermath of the Haitian earthquake of January 2010, as an avenue for critical reflection about the present. Tracing the students' responses to course readings and debates, the article considers the challenges of overcoming ethical disengagement in the classroom, and — in this context — both the advantages and disadvantages of an online learning environment, in a course that aimed specifically to generate answers to these questions: After the earthquake, how might a deeper knowledge of history allow us to make better sense of the present of Haiti, the international role of the United States, and our own position as historical observers? How might our knowledge be useful, in a renewed effort to achieve another possible world?
Carceral Quarantine at Guantánamo
Authors: Paik A. Naomi
Published: December 2012

This article examines the case of nearly 300 HIV-positive Haitian refugees the US state indefinitely detained on its Guantánamo naval base from 1991 to 1994. It argues that the predicament of these refugees emerged out of a nexus of historical threads that became entangled at Guantánamo, including the US state's near absolute exclusion of Haitian refugees, the legacy of antiblack and anti-Haitian racism, the discourses of disease that were linked to Haitian bodies, and the history of US (neo)imperial interests in the Caribbean. Its analysis centers on legal discourses and key federal court cases leading to US anti-Haitian refugee policies, including Haitian Refugee Center v. Civiletti (1980) and Haitian Centers Council v. Sale (1993), while examining the history of Haiti's political economy and relation to the United States, as well as discourses of race, nation, and contagion as they relate to Haitian migrants.
Haiti from the Outside In: A Review of Recent Literature
Authors: Smith Matthew J.
Published: December 2012

This review examines recent historiography on contemporary Haiti, specifically Kate Ramsey's The Spirits and the Law: Vodou and Power in Haiti (2011); Bernard Diederich's The Price of Blood: History of Repression and Rebellion in Haiti under Dr. François Duvalier, 1957 – 1961 and Murderers among Us: History of Repression and Rebellion in Haiti under Dr. François Duvalier, 1962 – 1971 (2011); Peter Hallward's Damming the Flood: Haiti and the Politics of Containment (2010); Philippe Zacaïr's Haiti and the Haitian Diaspora in the Wider Caribbean (2011); and Haïti-Haitii? Philosophical Reflections for Mental Decolonization (2011), by the former Catholic priest and president of Haiti, Jean-Bertrand Aristide.
Stabilizing Customer Abandonment in Many-Server Queues with Time-Varying Arrivals
Authors: Liu Yunan , Whitt Ward
Published: December 2012

An algorithm is developed to determine time-dependent staffing levels to stabilize the time-dependent abandonment probabilities and expected delays at positive target values in the Mt/GI/st + GI many-server queueing model, which has a nonhomogeneous Poisson arrival process (the Mt), has general service times (the first GI), and allows customer abandonment according to a general patience distribution (the +GI). New offered-load and modified-offered-load approximations involving infinite-server models are developed for that purpose. Simulations show that the approximations are effective. A many-server heavy-traffic limit in the efficiency-driven regime shows that (i) the proposed approximations achieve the goal asymptotically as the scale increases, and (ii) it is not possible to simultaneously stabilize the mean queue length in the same asymptotic regime.