bluuebunny/crossref_metadata_2025 huggingface dataset:
A remarkably stable TipE gene cluster: evolution of insect Para sodium channel auxiliary subunits
Authors: Li Jia , Waterhouse Robert M , Zdobnov Evgeny M
Published: December 2011

Background

First identified in fruit flies with temperature-sensitive paralysis phenotypes, theDrosophila melanogaster TipElocus encodes four voltage-gated sodium (NaV) channel auxiliary subunits. This cluster ofTipE-like genes on chromosome 3L, and a fifth family member on chromosome 3R, are important for the optional expression and functionality of the Para NaVchannel but appear quite distinct from auxiliary subunits in vertebrates. Here, we exploited available arthropod genomic resources to trace the origin ofTipE-like genes by mapping their evolutionary histories and examining their genomic architectures.

Results

We identified a remarkably conserved synteny block ofTipE-like orthologues with well-maintained local gene arrangements from 21 insect species. Homologues in the water flea,Daphnia pulex, suggest an ancestral pancrustacean repertoire of fourTipE-like genes; a subsequent gene duplication may have generated functional redundancy allowing gene losses in the silk moth and mosquitoes. Intronic nesting of the insectTipEgene cluster probably occurred following the divergence from crustaceans, but in the flour beetle and silk moth genomes the clusters apparently escaped from nesting. Across Pancrustacea,TipEgene family members have experienced intronic nesting, escape from nesting, retrotransposition, translocation, and gene loss events while generally maintaining their local gene neighbourhoods.D. melanogaster TipE-like genes exhibit coordinated spatial and temporal regulation of expression distinct from their host gene but well-correlated with their regulatory target, the Para NaVchannel, suggesting that functional constraints may preserve theTipEgene cluster. We identified homology between TipE-like NaVchannel regulators and vertebrate Slo-beta auxiliary subunits of big-conductance calcium-activated potassium (BKCa) channels, which suggests that ion channel regulatory partners have evolved distinct lineage-specific characteristics.

Conclusions

TipE-like genes form a remarkably conserved genomic cluster across all examined insect genomes. This study reveals likely structural and functional constraints on the genomic evolution of insectTipEgene family members maintained in synteny over hundreds of millions of years of evolution. The likely common origin of these NaVchannel regulators with BKCaauxiliary subunits highlights the evolutionary plasticity of ion channel regulatory mechanisms.
Adverse trends of cardiovascular risk factors among low risk populations (1983-1994) - a cohort study of workers and farmers in Guangzhou, China
Authors: Liu Xiaoqing , Mai Jinzhuang , Rao Xuxu , Zhuo Qiling , Guo Chengye , Gao Xiangmin , Wu Yong , Deng Mulan , Lin Shuguang
Published: December 2011

Background

The levels and trends of cardiovascular risk factors vary greatly throughout China. We examine 10-year trends of cardiovascular risk factors (1983-1994) and the factors related to these trends among low-risk cohorts of workers and farmers in Guangzhou, China.

Methods

This is a cohort study of 3,131 workers and 3,493 farmers aged 25-64 years at baseline with 10 years of follow-up. We performed a longitudinal analysis to account for the aging of the cohorts and the repeated measures of the same individual.

Results

At baseline the prevalence of overweight (including obese) ranged from 1.0% to 11.8%, hypertension ranged from 3.8% to 10.5%, and mean serum total cholesterol (TC) ranged from 155.4 mg/dl to 187.2 mg/dl. Although prevalence of smoking declined, blood pressure levels and body mass index (BMI) increased significantly, and lipid profiles changed unfavorably during the 10-year follow-ups. The prevalence of hypertension increased from 5.0 percentage points (female farmers) to 12.3 percentage points (male farmers). Mean TC increased significantly (e.g., +22.8 mg/dl and +17.0 mg/dl in male and female farmers, respectively). In the longitudinal data analyses, increase in BMI was associated with increase in blood pressure levels and TC. Significant adverse trends of risk factors persisted after adjustment for aging, education, BMI, smoking, and alcohol intake.

Conclusion

Urgent action is needed to prevent and reverse the unhealthy trends occurring among these low risk Chinese workers and farmers.
Healthcare costs in patients with metastatic lung cancer receiving chemotherapy
Authors: Vera-Llonch Montserrat , Weycker Derek , Glass Andrew , Gao Sue , Borker Rohit , Barber Beth , Oster Gerry
Published: December 2011

Background

To characterize healthcare resource utilization and costs in patients with metastatic lung cancer receiving chemotherapy in the US.

Methods

Using data from a large private multi-payer health insurance claims database (2000-2006), we identified all patients beginning chemotherapy for metastatic lung cancer. Healthcare resource use (inpatient, outpatient, medications) and costs were tallied over time from date of therapy initiation ("index date") to date of disenrollment from the health plan (in most instances, presumably due to death) or the end of the study period, whichever occurred first. Healthcare utilization and costs were characterized using Kaplan-Meier sample average methods.

Results

The study population consisted of 4068 patients; mean (SD) age was 65 (11) years. Over a median follow-up of 334 days, study subjects averaged 1.5 hospital admissions, 8.9 total inpatient days, and 69 physician office and hospital outpatient visits. Mean (95% CI) cumulative total healthcare costs were $125,849 ($120,228, $131,231). Costs of outpatient medical services and inpatient care constituted 34% and 20% of total healthcare costs, respectively; corresponding estimates for outpatient chemotherapy and other medication were 22% and 24%.

Conclusion

Our study sheds additional light on the burden of metastatic lung cancer among patients receiving chemotherapy, in terms of total cost thru end of life as well as component costs by setting and type of service, and may be useful in informing medical resource allocation in this patient population.
Do diabetes and depressed mood affect associations between obesity and quality of life in postmenopause? Results of the KORA-F3 Augsburg population study
Authors: Heidelberg Daniela A , Holle Rolf , Lacruz Maria E , Ladwig Karl-Heinz , von Lengerke Thomas
Published: December 2011

Background

To assess associations of obesity with health-related quality of life (HRQL) in postmenopausal women, and whether depressed mood and diabetes moderate these associations.

Methods

Survey of 983 postmenopausal women aged 35-74, general population, Augsburg region/Germany, 2004/2005. Body weight/height and waist/hip circumference were assessed anthropometrically and classified via BMI ≥ 30 as obese, and WHR ≥ 0.85 as abdominally obese (vs. not). Depressed mood was assessed by the Depression and Exhaustion-(DEEX-)scale, diabetes and postmenopausal status by self-report/medication, and HRQL by the SF-12.

Results

General linear models revealed negative associations of obesity and abdominal obesity with physical but not mental HRQL. Both forms of excess weight were associated with diabetes but not depressed mood. Moderation depended on the HRQL-domain in question. In non-diabetic women, depressed mood was found to amplify obesity-associated impairment in physical HRQL (mean "obese"-"non-obese" difference given depressed mood: -6.4, p < .001; among those without depressed mood: -2.5, p = .003). Reduced mental HRQL tended to be associated with obesity in diabetic women (mean "obese"-"non-obese" difference: -4.5, p = .073), independent of depressed mood. No interactions pertained to abdominal obesity.

Conclusions

In postmenopausal women, depressed mood may amplify the negative impact of obesity on physical HRQL, while diabetes may be a precondition for some degree of obesity-related impairments in mental HRQL.
Is there any relationship between physical activity level and patterns, and physical performance in children?
Authors: Blaes Aurélie , Baquet Georges , Fabre Claudine , Van Praagh Emmanuel , Berthoin Serge
Published: December 2011

Background

It is often assumed that physical activity (PA) and physical performance during childhood and adolescence are beneficial for health during adulthood, but a positive relationship between PA and physical performance has not been precisely clarified in children. The lack or the weakness of the relationships between PA and physical performance could be due to the measure of PA. If the use of accelerometry is considered as an objective and common measure of PA, the real patterns of children's habitual PA must be reflected. The aim of this study was to investigate the relationship between the levels and patterns of PA assessed with high frequency accelerometry and physical performance in young children.

Methods

Eighty-six boys and 101 girls aged 6-12 years participated in this study. Physical activity was measured over a 7-day period, using a 5-s epoch. Physical performance was assessed by means of EUROFIT tests (anthropometrics, standing broad jump, the 10 × 5 meter shuttle run, the sit-and-reach, the handgrip, the number of sit-ups in 30 seconds, the 20-meter shuttle run).

Results

No relationship was found between PA and physical performance. In boys only, body fatness was negatively associated with vigorous PA (r = -0.38, p < 0.001) and very high PA (r = -0.35, p < 0.01), in contrast to light PA (r = 0.28, p < 0.01), which was positively related to body fatness.

Conclusion

In 6- to- 12 year- old children, the more active children were not the fittest. Our results also underline the need for uniformity in approach to measurement of PA, body composition and health-related fitness between studies.
Expression of the Epigenetic factor BORIS (CTCFL) in the Human Genome
Authors: de Necochea-Campion Rosalia , Ghochikyan Anahit , Josephs Steven F , Zacharias Shelly , Woods Erik , Karimi-Busheri Feridoun , Alexandrescu Doru T , Chen Chien-Shing , Agadjanyan Michael G , Carrier Ewa
Published: December 2011

BORIS, or CTCFL, the so called Brother of the Regulator of Imprinted Sites because of the extensive homology in the central DNA binding region of the protein to the related regulator, CTCF, is expressed in early gametogenesis and in multiple cancers but not in differentiated somatic cells. Thus it is a member of the cancer testes antigen group (CTAs). Since BORIS and CTCF target common DNA binding sites, these proteins function on two levels, the first level is their regulation via the methylation context of the DNA target site and the second level is their distinct and different epigenetic associations due to differences in the non-homologous termini of the proteins. The regulation on both of these levels is extensive and complex and the sphere of influence of each of these proteins is associated with vastly different cellular signaling processes. On the level of gene expression, BORIS has three known promoters and multiple spliced mRNAs which adds another level of complexity to this intriguing regulator. BORIS expression is observed in the majority of cancer tissues and cell lines analyzed up to today. The expression profile and essential role of BORIS in cancer make this molecule very attractive target for cancer immunotherapy. This review summarizes what is known about BORIS regarding its expression, structure, and function and then presents some theoretical considerations with respect to its genome wide influence and its potential for use as a vaccine for cancer immunotherapy.
Raman enhancement of rhodamine adsorbed on Ag nanoparticles self-assembled into nanowire-like arrays
Authors: Panagopoulou Marianthi , Pantiskos Nikolaos , Photopoulos Panos , Tang Jun , Tsoukalas Dimitris , Raptis Yannis S
Published: December 2011

This work reports on Raman scattering of rhodamine (R6G) molecules absorbed on either randomly distributed or grating-like arrays of approximately 8-nm Ag nanoparticles developed by inert gas aggregation. Optimal growth and surface-enhanced Raman scattering (SERS) parameters have been obtained for the randomly distributed nanoparticles, while effects related to the aging of the silver nanoparticles were studied. Grating-like arrays of nanoparticles have been fabricated using line arrays templates formed either by fracture-induced structuring or by standard lithographic techniques. Grating structures fabricated by both methods exhibit an enhancement of the SERS signal, in comparison to the corresponding signal from randomly distributed Ag nanoparticles, as well as a preferential enhancement in the areas of the sharp features, and a dependence on the polarization direction of the incident exciting laser beam, with respect to the orientation of the gratings structuring. The observed spectroscopic features are consistent with a line-arrangement of hot-spots due to the self- alignment of metallic nanoparticles, induced by the grating-like templates.
Viral and cellular requirements for the budding of Feline Endogenous Retrovirus RD-114
Authors: Fukuma Aiko , Abe Masumi , Urata Shuzo , Yoshikawa Rokusuke , Morikawa Yuko , Miyazawa Takayuki , Yasuda Jiro
Published: December 2011

Background

RD-114 virus is a feline endogenous retrovirus and produced as infectious viruses in some feline cell lines. Recently, we reported the contamination of an infectious RD-114 virus in a proportion of live attenuated vaccines for dogs and cats. It is very difficult to completely knock out the RD-114 proviruses from cells, as endogenous retroviruses are usually integrated multiply into the host genome. However, it may be possible to reduce the risk of contamination of RD-114 virus by regulating the viral release from cells.

Results

In this study, to understand the molecular mechanism of RD-114 virus budding, we attempted to identify the viral and cellular requirements for RD-114 virus budding. Analyses of RD-114 L-domain mutants showed that the PPPY sequence in the pp15 region of Gag plays a critical role in RD-114 virus release as viral L-domain. Furthermore, we investigated the cellular factors required for RD-114 virus budding. We demonstrated that RD-114 virus release was inhibited by overexpression of dominant negative mutants of Vps4A, Vps4B, and WWP2.

Conclusions

These results strongly suggest that RD-114 budding utilizes the cellular multivesicular body sorting pathway similar to many other retroviruses.
Heart rate variability analysis in sheep affected by transmissible spongiform encephalopathies
Authors: Konold Timm , Bone Gemma E
Published: December 2011

Background

The function of the autonomic nervous system can be assessed by determining heart rate variability (HRV), which is impaired in some brainstem diseases in humans. Transmissible spongiform encephalopathies (TSEs) in sheep are diseases characterised by accumulation of disease-associated prion protein in the brainstem, including nuclei of the parasympathetic nervous system. This study was undertaken to assess whether analysis of HRV can be used as an aid in the diagnosis of TSEs in clinically affected, naturally or experimentally infected sheep.

Findings

When HRV indices were compared between 41 clinical TSE cases (18 sheep infected with scrapie and 23 sheep infected with bovine spongiform encephalopathy), 11 control sheep and six sheep reported as scrapie suspects or dosed with BSE brain homogenate, which were not confirmed as TSE cases by postmortem tests, no significant differences were found between the groups. Median heart rate was significantly different but only when sheep were grouped by gender: it was higher in female TSE cases than in control sheep and higher in female than castrated male ovine classical BSE cases.

Conclusions

HRV analysis was not useful as a diagnostic aid for TSEs of sheep.
Measurement of metabolic tumor volume: static versus dynamic FDG scans
Authors: Cheebsumon Patsuree , van Velden Floris HP , Yaqub Maqsood , Hoekstra Corneline J , Velasquez Linda M , Hayes Wendy , Hoekstra Otto S , Lammertsma Adriaan A , Boellaard Ronald
Published: December 2011

Background

Metabolic tumor volume assessment using positron-emission tomography [PET] may be of interest for both target volume definition in radiotherapy and monitoring response to therapy. It has been reported, however, that metabolic volumes derived from images of metabolic rate of glucose (generated using Patlak analysis) are smaller than those derived from standardized uptake value [SUV] images. The purpose of this study was to systematically compare metabolic tumor volume assessments derived from SUV and Patlak images using a variety of (semi-)automatic tumor delineation methods in order to identify methods that can be used reliably on (whole body) SUV images.

Methods

Dynamic [18F]-fluoro-2-deoxy-D-glucose [FDG] PET data from 10 lung and 8 gastrointestinal cancer patients were analyzed retrospectively. Metabolic tumor volumes were derived from both Patlak and SUV images using five different types of tumor delineation methods, based on various thresholds or on a gradient.

Results

In general, most tumor delineation methods provided more outliers when metabolic volumes were derived from SUV images rather than Patlak images. Only gradient-based methods showed more outliers for Patlak-based tumor delineation. Median measured metabolic volumes derived from SUV images were larger than those derived from Patlak images (up to 59% difference) when using a fixed percentage threshold method. Tumor volumes agreed reasonably well (< 26% difference) when applying methods that take local signal-to-background ratio [SBR] into account.

Conclusion

Large differences may exist in metabolic volumes derived from static and dynamic FDG image data. These differences depend strongly on the delineation method used. Delineation methods that correct for local SBR provide the most consistent results between SUV and Patlak images.
Twist Modulates Human Trophoblastic Cell Invasion via Regulation of N-Cadherin
Authors: Ng York Hunt , Zhu Hua , Leung Peter C. K.
Published: December 2011

The invasion of extravillous cytotrophoblasts (EVT) into the underlying maternal tissues and vasculature is a key step in human placentation. The molecular mechanisms involved in the development of the invasive phenotype of EVT include many that were first discovered for their role in cancer cell metastasis. Previous studies have demonstrated that N-cadherin and its regulatory transcription factor Twist play important roles in the onset and progression of cancers, but their roles in human trophoblastic cell invasion is not clear. The goal of the study was to examine the role of Twist and N-cadherin in human trophoblastic cell invasion. Twist and N-cadherin mRNA and protein levels were determined by RT-PCR and Western blotting in human placental tissues, highly invasive EVT, and poorly invasive JEG-3 and BeWo cells. Whether IL-1β and TGF-β1 regulate Twist mRNA and protein levels in the EVT was also examined. A small interfering RNA strategy was employed to determine the role of Twist and N-cadherin in HTR-8/SVneo cell invasion. Matrigel assays were used to assess cell invasion. Twist and N-cadherin were highly expressed in EVT but were poorly expressed in JEG-3 and BeWo cells. IL-1β and TGF-β1 differentially regulated Twist expression in EVT in a time- and concentration-dependent manner. Small interfering RNA specific for Twist decreased N-cadherin and reduced invasion of HTR-8/SVneo cells. Similarly, a reduction in N-cadherin decreased the invasive capacity of HTR-8/SVneo cells. Twist is an upstream regulator of N-cadherin-mediated invasion of human trophoblastic cells.
Role of the Glyoxalase System in Astrocyte-Mediated Neuroprotection
Authors: Bélanger Mireille , Yang Jiangyan , Petit Jean-Marie , Laroche Thierry , Magistretti Pierre J. , Allaman Igor
Published: December 2011

The glyoxalase system is the most important pathway for the detoxification of methylglyoxal (MG), a highly reactive dicarbonyl compound mainly formed as a by-product of glycolysis. MG is a major precursor of advanced glycation end products (AGEs), which are associated with several neurodegenerative disorders. Although the neurotoxic effects of MG and AGEs are well characterized, little is known about the glyoxalase system in the brain, in particular with regards to its activity in different neural cell types. Results of the present study reveal that both enzymes composing the glyoxalase system [glyoxalase-1 (Glo-1) and Glo-2] were highly expressed in primary mouse astrocytes compared with neurons, which translated into higher enzymatic activity rates in astrocytes (9.9- and 2.5-fold, respectively). The presence of a highly efficient glyoxalase system in astrocytes was associated with lower accumulation of AGEs compared with neurons (as assessed by Western blotting), a sixfold greater resistance to MG toxicity, and the capacity to protect neurons against MG in a coculture system. In addition, Glo-1 downregulation using RNA interference strategies resulted in a loss of viability in neurons, but not in astrocytes. Finally, stimulation of neuronal glycolysis via lentiviral-mediated overexpression of 6-phosphofructose-2-kinase/fructose-2,6-bisphosphatase-3 resulted in increased MG levels and MG-modified proteins. Since MG is largely produced through glycolysis, this suggests that the poor capacity of neurons to upregulate their glycolytic flux as compared with astrocytes may be related to weaker defense mechanisms against MG toxicity. Accordingly, the neuroenergetic specialization taking place between these two cell types may serve as a protective mechanism against MG-induced neurotoxicity.
Specific Protein Kinase C Isoforms Are Required for Rod Photoreceptor Differentiation
Authors: Pinzon-Guzman Carolina , Zhang Samuel Shao-Min , Barnstable Colin J.
Published: December 2011

The protein kinase C (PKC) family of enzymes regulates cell physiology through phosphorylation of serine and threonine residues of many proteins in most cell types. Here we identify PKC-β1 and PKC-γ as isoforms that are essential for rod photoreceptor differentiation in mouse retinas. Usingex vivoretinal explants, we found that phorbol ester 12-myristate 13-acetate and insulin-like growth factor 1 (IGF1) induced rod differentiation, as defined by opsin or Crx expression, in a PKC-dependent manner days ahead of rod development in untreated explants. PKC-β1 and PKC-γ were colocalized with proliferating cell nuclear antigen (PCNA)- and STAT3-positive progenitors through the later differentiation period. Pharmacological or genetic inhibition of either isoform resulted in a partial reduction in the appearance of rods, whereas removing both isoforms resulted in their complete absence. Furthermore, a significant decline of STAT3 tyrosine phosphorylation was observed by activation of PKC, while inhibition of PKC resulted in an increase of phosphorylated STAT3 along with a delayed cell cycle exit of progenitors with prolonged PCNA expression. In adult retinas, IGF1 activates PI-3 kinase (PI3K), but in neonatal retinas its action is identical to the action of an PI3K inhibitor. These data unveil a novel signaling cascade that coordinates and regulates rod differentiation through specific PKC isoforms in mammals.
Interactions between “What” and “When” in the Auditory System: Temporal Predictability Enhances Repetition Suppression
Authors: Costa-Faidella Jordi , Baldeweg Torsten , Grimm Sabine , Escera Carles
Published: December 2011

Neural activity in the auditory system decreases with repeated stimulation, matching stimulus probability in multiple timescales. This phenomenon, known as stimulus-specific adaptation, is interpreted as a neural mechanism of regularity encoding aiding auditory object formation. However, despite the overwhelming literature covering recordings from single-cell to scalp auditory-evoked potential (AEP), stimulation timing has received little interest. Here we investigated whether timing predictability enhances the experience-dependent modulation of neural activity associated with stimulus probability encoding. We used human electrophysiological recordings in healthy participants who were exposed to passive listening of sound sequences. Pure tones of different frequencies were delivered in successive trains of a variable number of repetitions, enabling the study of sequential repetition effects in the AEP. In the predictable timing condition, tones were delivered with isochronous interstimulus intervals; in the unpredictable timing condition, interstimulus intervals varied randomly. Our results show that unpredictable stimulus timing abolishes the early part of the repetition positivity, an AEP indexing auditory sensory memory trace formation, while leaving the later part (∼>200 ms) unaffected. This suggests that timing predictability aids the propagation of repetition effects upstream the auditory pathway, most likely from association auditory cortex (including the planum temporale) toward primary auditory cortex (Heschl's gyrus) and beyond, as judged by the timing of AEP latencies. This outcome calls for attention to stimulation timing in future experiments regarding sensory memory trace formation in AEP measures and stimulus probability encoding in animal models.
Correlated Variations in the Parameters That Regulate Dendritic Calcium Signaling in Mouse Retinal Ganglion Cells
Authors: Gartland Andrew J. , Detwiler Peter B.
Published: December 2011

The amplitude and time course of stimulus-evoked second messenger signals carried by intracellular changes in free calcium ([Ca]free) depend on the total influx of Ca2+, the fraction bound to endogenous buffer and the rate of extrusion. Estimates of the values of these three parameters in proximal dendrites of 15 mouse α retinal ganglion cells were made using the “added buffer” method and found to vary greatly from one experiment to the next. The variations in the measured parameters were strongly correlated across the sample of cells. This reduced the variability in the amplitude and time course of the dendritic Ca2+signal and suggests that the expression of Ca2+channels, binding proteins and extrusion mechanisms is homeostatically coordinated to maintain the amplitude and kinetics of the Ca2+signal within a physiologically appropriate range.
Low Energy Electron Point Source Microscopy of Two-Dimensional Carbon Nanostructures
Authors: Vieker Henning , Beyer André , Blank Holger , Weber Dirk Henning , Gerthsen Dagmar , Gölzhäuser Armin
Published: December 2011

1 nm thick carbon nanomembranes (CNMs) are investigated with Low Energy Electron Point Source (LEEPS) microscopy. A CNM consists of a freely suspended carbon film made from a cross-linked self-assembled monolayer (SAM). During thermal annealing the CNM transforms into nanocrystalline graphene.We determined the electron transmissivity of CNMs from the LEEPS images. After pyrolysis, the LEEPS images showed clear differences compared to pristine CNMs. Upon annealing above 800 ºC the LEEPS images exhibit distinct features that are related to the structural transition. A comparison of LEEPS images with transmission electron micrographs of the same regions and features demonstrates that both microscopic techniques reveal similar structural features.
High Resolution IR Spectroscopy of the C–H Stretch Bands of Benzene Monomer and Dimer in Helium Nanodroplets
Authors: Poerschke Torsten , Habig Daniel , Havenith Martina
Published: December 2011

The IR spectrum of benzene and benzene dimer embedded in superfluid helium droplets in the region of the C–H stretch vibration (3000–3110 cm-1) was observed. By analyzing the pressure dependence of the spectra it was possible to assign these spectra to benzene monomer and dimer.

Based on a comparison of the observed position of the dimer bands to experimental bands recorded in the gas phase and to theoretical frequency predictions the authors assign these to the tilted T-shaped benzene dimer structure. None of the other two possible structures (PD or PTS) were found. The above assignment is firm.

For the monomer, we find in helium nanodroplets a splitting of the ν
8+ν
19
combination band observed in the gas phase. We assign this to an additional Fermi resonance which is caused by the matrix shift in helium nanodroplets.
Cannulating a Dissecting Aorta Using Ultrasound-Epiaortic and Transesophageal Guidance
Authors: Attaran Saina , Safar Maria , Saleh Hesham Zayed , Field Mark , Kuduvalli Manoj , Oo Aung
Published: December 2011

Management of acute Stanford type A aortic dissection remains a major surgical challenge. Directly cannulating the ascending aorta provides a rapid establishment of cardiopulmonary bypass but consists of risks such as complete rupture of the aorta, false lumen cannulation, subsequent malperfusion and propagation of the dissection.

We describe a technique of cannulating the ascending aorta in patients with acute aortic dissection that can be performed rapidly in hemodynamically unstable patients under ultrasound-epiaortic and transesophageal (TEE) guidance.
Avoidance of Aortic Side-Clamping for Proximal Bypass Anastomoses: Better Short-term Outcome?
Authors: Wilhelm Markus J. , Syburra Thomas , Furrer Lukas , Frielingsdorf J�rgen , Odavic Dragan , Graves Kirk , Genoni Michele
Published: December 2011

Objectives: The benefit of off-pump coronary artery bypass (OPCAB) surgery may be reduced by strokes caused by microemboli produced after aortic side-clamping for proximal bypass anastomoses. The Heartstring device allows constructing proximal bypass anastomoses without side-clamping of the aorta.

Methods: This retrospective study describes 260 consecutive patients who underwent OPCAB surgery; 442 proximal anastomoses were performed with the Heartstring device in this series. Ten percent of the patients were randomly sampled before discharge to undergo a coronary angiogram for assessment of graft patency.

Results: Intraoperative Doppler measurements confirmed regular bypass function. Early mortality occurred in 4 patients (1.5%), and stroke occurred in 2 patients (0.8%). Device-related bleeding was negligible, and there were no cases of aortic dissection. Perioperative ischemia occurred in 8 patients (3.1%). Predischarge coronary angiography evaluations in 25 of the patients (of 260) showed that all 42 Heartstring-assisted anastomoses (of 442) were patent. Conclusions: Clampless performance of proximal bypass anastomoses combined with OPCAB is associated with a very low incidence of stroke complications. Short-term follow-up has shown excellent results regarding bypass patency and other adverse events. Prospective randomized trials are required to confirm the advantage of this technique.
A Learning Curve in Bentall and De Bono Procedure with the Use of the Risk-Adjusted Cumulative Sum Analysis Based on the Japan SCORE
Authors: Song Min-Ho
Published: December 2011

Objective: The risk-adjusted cumulative sum analysis of an individual surgical learning curve for the Bentall and De Bono procedure on aortic root pathologies was used to monitor and enhance quality control.

Methods: From April 2004 to March 2009, 20 consecutive patients were operated upon by a single surgeon for aortic root pathologies by means of the Bentall and De Bono procedure. Operative variables, mortality, and major morbidities were analyzed. The learning curve was calculated using descriptive statistics and cumulative sum failure observed minus expected failure rate derived from the Japan SCORE calculator.

Results: In this series, the Japan SCORE calculator expected 3.91% � 5.14% of 30-day operative mortality rate and 16.74 � 13.47% of 30-day operative mortality and morbidity. In reality, there was no operative and in-hospital death. Major postoperative morbidity rate was 15.0% (3 patients). The risk-adjusted cumulative sum analysis revealed that the learning curve of mortality was downward below the lower 95% confidence interval throughout all the patients and that of morbidity was upward till the seventh case and remained downward thereafter. The polynomial approximation coefficient analysis revealed a significant negative correlation between aortic cross-clamp time, cardiopulmonary time, and operation time and case load.

Conclusions: The Bentall and De Bono procedure for aortic root pathologies was performed at the professionally permissive level from the beginning, even in a low-volume environment. It showed one good example of a learning curve. The risk-adjusted cumulative sum analysis based on the Japan SCORE was a very useful tool for monitoring the performance.
Mitral Valve Repair is Underused in Patients with Hypertrophic Obstructive Cardiomyopathy
Authors: Vassileva Christina M. , Boley Theresa , Markwell Stephen , Hazelrigg Stephen
Published: December 2011

Background: The optimal surgical approach for patients with hypertrophic obstructive cardiomyopathy (HOCM) with concomitant mitral valve (MV) regurgitation has remained controversial. The purpose of this study was to use the largest all-payer database in the United States to examine the strategy most commonly used for the correction of mitral valve pathology in the setting of HOCM.

Methods: The Nationwide Inpatient Sample (NIS) database was searched from 2005 to 2008 to identify patients with a diagnosis of HOCM (ICD-9-CM code 425.1) who underwent MV repair (ICD-9-CM code 35.12) or replacement (ICD-9-CM codes 35.23 and 35.24). HOCM patients who underwent MV repair and those who underwent MV replacement were compared with respect to baseline characteristics, repair rates, hospital mortality, and length of stay (LOS).

Results: MV repair was performed in 17.2% of cases (219/1255). Repair rates did not show a significantly increasing trend over time (P = .1419). The median LOS was significantly longer for replacement than for repair (11 days versus 7 days, P = .0001). The mortality rate for patients who underwent repair was 0.00%, compared with 11.18% for those who underwent replacement (P < .05).

Conclusions: The majority of patients with a HOCM diagnosis underwent MV replacement for the correction of MV pathology. Referral to centers with special expertise in treating patients with HOCM may positively affect the operative outcomes of this patient subset.
Organization and Evolution of Subtelomeric Satellite Repeats in the Potato Genome
Authors: Torres Giovana A , Gong Zhiyun , Iovene Marina , Hirsch Cory D , Buell C Robin , Bryan Glenn J , Novák Petr , Macas Jiří , Jiang Jiming
Published: December 2011

Subtelomeric domains immediately adjacent to telomeres represent one of the most dynamic and rapidly evolving regions in eukaryotic genomes. A common feature associated with subtelomeric regions in different eukaryotes is the presence of long arrays of tandemly repeated satellite sequences. However, studies on molecular organization and evolution of subtelomeric repeats are rare. We isolated two subtelomeric repeats, CL14 and CL34, from potato (Solanum tuberosum). The CL14 and CL34 repeats are organized as independent long arrays, up to 1-3 Mb, of 182 bp and 339 bp monomers, respectively. The CL14 and CL34 repeat arrays are directly connected with the telomeric repeats at some chromosomal ends. The CL14 repeat was detected at the subtelomeric regions among highly diverged Solanum species, including tomato (Solanum lycopersicum). In contrast, CL34 was only found in potato and its closely related species. Interestingly, the CL34 repeat array was always proximal to the telomeres when both CL14 and CL34 were found at the same chromosomal end. In addition, the CL34 repeat family showed more sequence variability among monomers compared with the CL14 repeat family. We conclude that the CL34 repeat family emerged recently from the subtelomeric regions of potato chromosomes and is rapidly evolving. These results provide further evidence that subtelomeric domains are among the most dynamic regions in eukaryotic genomes.
Rediscovery by Whole Genome Sequencing: Classical Mutations and Genome Polymorphisms inNeurospora crassa
Authors: McCluskey Kevin , Wiest Aric E , Grigoriev Igor V , Lipzen Anna , Martin Joel , Schackwitz Wendy , Baker Scott E
Published: December 2011

Classical forward genetics has been foundational to modern biology, and has been the paradigm for characterizing the role of genes in shaping phenotypes for decades. In recent years, reverse genetics has been used to identify the functions of genes, via the intentional introduction of variation and subsequent evaluation in physiological, molecular, and even population contexts. These approaches are complementary and whole genome analysis serves as a bridge between the two. We report in this article the whole genome sequencing of eighteen classical mutant strains of Neurospora crassa and the putative identification of the mutations associated with corresponding mutant phenotypes. Although some strains carry multiple unique nonsynonymous, nonsense, or frameshift mutations, the combined power of limiting the scope of the search based on genetic markers and of using a comparative analysis among the eighteen genomes provides strong support for the association between mutation and phenotype. For ten of the mutants, the mutant phenotype is recapitulated in classical or gene deletion mutants in Neurospora or other filamentous fungi. From thirteen to 137 nonsense mutations are present in each strain and indel sizes are shown to be highly skewed in gene coding sequence. Significant additional genetic variation was found in the eighteen mutant strains, and this variability defines multiple alleles of many genes. These alleles may be useful in further genetic and molecular analysis of known and yet-to-be-discovered functions and they invite new interpretations of molecular and genetic interactions in classical mutant strains.
Integrating Rare-Variant Testing, Function Prediction, and Gene Network in Composite Resequencing-Based Genome-Wide Association Studies (CR-GWAS)
Authors: Zhu Chengsong , Li Xianran , Yu Jianming
Published: December 2011

High-density array-based genome-wide association studies (GWAS) are complemented by exome sequencing and whole-genome resequencing-based association studies. Here we present a composite resequencing-based genome-wide association study (CR-GWAS) strategy that systematically exploits collective biological information and analytical tools for a robust analysis. We showcased the utility of this strategy by using Arabidopsis (Arabidopsis thaliana) resequencing data. Bioinformatic predictions of biological function alteration at each locus were integrated into the process of association testing of both common and rare variants for complex traits with a suite of statistics. Significant signals were then filtered with a priori candidate loci generated from genome database and gene network models to obtain a posteriori candidate loci. A probabilistic gene network (AraNet) that interrogates network neighborhoods of genes was then used to expand the filtering power to examine the significant testing signals. Using this strategy, we confirmed the known true positives and identified several new promising associations. Promising genes (AP1, FCA, FRI, FLC, FLM, SPL5, FY, and DCL2) were shown to control for flowering time through either common variants or rare variants within a diverse set of Arabidopsis accessions. Although many of these candidate genes were cloned earlier with mutational studies, identifying their allele variation contribution to overall phenotypic variation among diverse natural accessions is critical. Our rare allele testing established a greater number of connections than previous analyses in which this issue was not addressed. More importantly, our results demonstrated the potential of integrating various biological, statistical, and bioinformatic tools into complex trait dissection.
Polymorphism and Divergence in Two Willow Species,Salix viminalisL. andSalix schweriniiE. Wolf
Authors: Berlin Sofia , Fogelqvist Johan , Lascoux Martin , Lagercrantz Ulf , Rönnberg-Wästljung Ann Christin
Published: December 2011

We investigated species divergence, present and past gene flow, levels of nucleotide polymorphism, and linkage disequilibrium in two willows from the plant genus Salix. Salix belongs together with Populus to the Salicaceae family; however, most population genetic studies of Salicaceae have been performed in Populus, the model genus in forest biology. Here we present a study on two closely related willow species Salix viminalis and S. schwerinii, in which we have resequenced 33 and 32 nuclear gene segments representing parts of 18 nuclear loci in 24 individuals for each species. We used coalescent simulations and estimated the split time to around 600,000 years ago and found that there is currently limited gene flow between the species. Mean intronic nucleotide diversity across gene segments was slightly higher in S. schwerinii (πi = 0.00849) than in S. viminalis (πi = 0.00655). Compared with other angiosperm trees, the two willows harbor intermediate levels of silent polymorphisms. The decay of linkage disequilibrium was slower in S. viminalis compared with S. schwerinii, and we speculate that this is due to different demographic histories as S. viminalis has been partly domesticated in Europe.
SAD-3, a Putative Helicase Required for Meiotic Silencing by Unpaired DNA, Interacts with Other Components of the Silencing Machinery
Authors: Hammond Thomas M , Xiao Hua , Boone Erin C , Perdue Tony D , Pukkila Patricia J , Shiu Patrick K T
Published: December 2011

In Neurospora crassa, genes lacking a pairing partner during meiosis are suppressed by a process known as meiotic silencing by unpaired DNA (MSUD). To identify novel MSUD components, we have developed a high-throughput reverse-genetic screen for use with the N. crassa knockout library. Here we describe the screening method and the characterization of a gene (sad-3) subsequently discovered. SAD-3 is a putative helicase required for MSUD and sexual spore production. It exists in a complex with other known MSUD proteins in the perinuclear region, a center for meiotic silencing activity. Orthologs of SAD-3 include Schizosaccharomyces pombe Hrr1, a helicase required for RNAi-induced heterochromatin formation. Both SAD-3 and Hrr1 interact with an RNA-directed RNA polymerase and an Argonaute, suggesting that certain aspects of silencing complex formation may be conserved between the two fungal species.
Variable Transposition of Eight Maize Activator (Ac) Elements Located on the Short Arm of Chromosome 1
Authors: Sheridan William F
Published: December 2011

Eight Activator (Ac) transposable elements mapped to the maize chromosome arm 1S were assessed for Ac transposition rates. For each of the Ac stocks, plants homozygous for the single Ac element and the Ds reporter r1-sc:m3 on chromosome 10 were crossed as females by a homozygous r1-sc:m3 tester color-converted W22 line. The resulting ears produced mostly coarsely spotted kernels and a low frequency of either near-colorless fine-spotted kernels or nonspotted kernels. The relative frequency of these two types of near-colorless kernels differed among the eight Ac stocks. The extent to which increased Ac dosage results in nonspotted kernels may be Ac-specific. Although all of the Ac elements are in near-isogenic inbred W22 lines, they varied to a large extent in their transposition frequency. These differences might possibly result from structural differences among the Ac elements. Because one pair of Ac elements derived from Ac33 on chromosome arm 5S differed about 13-fold in transposition frequency and a second pair of Ac elements derived from Ac12 on chromosome arm 1S differed about 3-fold in transposition frequency, this is not a likely explanation for all eight Ac elements. The data presented here support the notion that the differences in transposition frequency of the eight Ac elements may be a reflection of variability in Ac transcription or accessibility of the transposase to the Ac element, resulting from differences in the chromatin environments wherein the Ac elements are located. This is the first report of variability in transposition rates among different Ac donor lines.
Genome-Scale Analysis of Programmed DNA Elimination Sites in Tetrahymena thermophila
Authors: Fass Joseph N , Joshi Nikhil A , Couvillion Mary T , Bowen Josephine , Gorovsky Martin A , Hamilton Eileen P , Orias Eduardo , Hong Kyungah , Coyne Robert S , Eisen Jonathan A , Chalker Douglas L , Lin Dawei , Collins Kathleen
Published: December 2011

Genetically programmed DNA rearrangements can regulate mRNA expression at an individual locus or, for some organisms, on a genome-wide scale. Ciliates rely on a remarkable process of whole-genome remodeling by DNA elimination to differentiate an expressed macronucleus (MAC) from a copy of the germline micronucleus (MIC) in each cycle of sexual reproduction. Here we describe results from the first high-throughput sequencing effort to investigate ciliate genome restructuring, comparing Sanger long-read sequences from a Tetrahymena thermophila MIC genome library to the MAC genome assembly. With almost 25% coverage of the unique-sequence MAC genome by MIC genome sequence reads, we created a resource for positional analysis of MIC-specific DNA removal that pinpoints MAC genome sites of DNA elimination at nucleotide resolution. The widespread distribution of internal eliminated sequences (IES) in promoter regions and introns suggests that MAC genome restructuring is essential not only for what it removes (for example, active transposons) but also for what it creates (for example, splicing-competent introns). Consistent with the heterogeneous boundaries and epigenetically modulated efficiency of individual IES deletions studied to date, we find that IES sites are dramatically under-represented in the ∼25% of the MAC genome encoding exons. As an exception to this general rule, we discovered a previously unknown class of small (<500 bp) IES with precise elimination boundaries that can contribute the 3′ exon of an mRNA expressed during genome restructuring, providing a new mechanism for expanding mRNA complexity in a developmentally regulated manner.
Double-Strand Break Repair and Holliday Junction Processing Are Required for Chromosome Processing in Stationary-Phase Escherichia coli Cells
Authors: Williams Ashley B , Hetrick Kyle M , Foster Patricia L
Published: December 2011

As nutrients are depleted and cell division ceases in batch cultures of bacteria, active processes are required to ensure that each cell has a complete copy of its genome. How chromosome number is manipulated and maintained in nondividing bacterial cells is not fully understood. Using flow cytometric analysis of cells from different growth phases, we show that the Holliday junction–processing enzymes RuvABC and RecG, as well as RecBCD, the enzyme complex that initiates DNA double-strand break repair, are required to establish the normal distribution of fluorescent peaks, which is commonly accepted to reflect the distribution of chromosome numbers. Our results reveal that these proteins are required for the proper processing of chromosomes in stationary phase.