bluuebunny/crossref_metadata_2025 huggingface dataset:
The seipin complex Fld1/Ldb16 stabilizes ER–lipid droplet contact sites
Authors: Grippa Alexandra , Buxó Laura , Mora Gabriel , Funaya Charlotta , Idrissi Fatima-Zahra , Mancuso Francesco , Gomez Raul , Muntanyà Júlia , Sabidó Eduard , Carvalho Pedro
Published: November 2015

Lipid droplets (LDs) are storage organelles consisting of a neutral lipid core surrounded by a phospholipid monolayer and a set of LD-specific proteins. Most LD components are synthesized in the endoplasmic reticulum (ER), an organelle that is often physically connected with LDs. How LD identity is established while maintaining biochemical and physical connections with the ER is not known. Here, we show that the yeast seipin Fld1, in complex with the ER membrane protein Ldb16, prevents equilibration of ER and LD surface components by stabilizing the contact sites between the two organelles. In the absence of the Fld1/Ldb16 complex, assembly of LDs results in phospholipid packing defects leading to aberrant distribution of lipid-binding proteins and abnormal LDs. We propose that the Fld1/Ldb16 complex facilitates the establishment of LD identity by acting as a diffusion barrier at the ER–LD contact sites.
Transducing oxidative stress to death signals in neurons
Authors: Cao Xu , Fang Yanshan
Published: November 2015

Accumulation of reactive oxygen species (ROS) has been associated with aging and neurodegenerative diseases. Nevertheless, how elevated ROS levels cause neurodegeneration is unclear. In this issue, Wakatsuki et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201506102) delineate how oxidative stress is transduced into death signals, leading to neuronal apoptosis and axonal degeneration.
The interactome challenge
Authors: Aitchison John D. , Rout Michael P.
Published: November 2015

The properties of living cells are mediated by a huge number of ever-changing interactions of their component macromolecules forming living machines; collectively, these are termed the interactome. Pathogenic alterations in interactomes mechanistically underlie diseases. Therefore, there exists an essential need for much better tools to reveal and dissect interactomes. This need is only now beginning to be met.
A general mechanism for drug promiscuity: Studies with amiodarone and other antiarrhythmics
Authors: Rusinova Radda , Koeppe Roger E. , Andersen Olaf S.
Published: November 2015

Amiodarone is a widely prescribed antiarrhythmic drug used to treat the most prevalent type of arrhythmia, atrial fibrillation (AF). At therapeutic concentrations, amiodarone alters the function of many diverse membrane proteins, which results in complex therapeutic and toxicity profiles. Other antiarrhythmics, such as dronedarone, similarly alter the function of multiple membrane proteins, suggesting that a multipronged mechanism may be beneficial for treating AF, but raising questions about how these antiarrhythmics regulate a diverse range of membrane proteins at similar concentrations. One possible mechanism is that these molecules regulate membrane protein function by altering the common environment provided by the host lipid bilayer. We took advantage of the gramicidin (gA) channels’ sensitivity to changes in bilayer properties to determine whether commonly used antiarrhythmics—amiodarone, dronedarone, propranolol, and pindolol, whose pharmacological modes of action range from multi-target to specific—perturb lipid bilayer properties at therapeutic concentrations. Using a gA-based fluorescence assay, we found that amiodarone and dronedarone are potent bilayer modifiers at therapeutic concentrations; propranolol alters bilayer properties only at supratherapeutic concentration, and pindolol has little effect. Using single-channel electrophysiology, we found that amiodarone and dronedarone, but not propranolol or pindolol, increase bilayer elasticity. The overlap between therapeutic and bilayer-altering concentrations, which is observed also using plasma membrane–like lipid mixtures, underscores the need to explore the role of the bilayer in therapeutic as well as toxic effects of antiarrhythmic agents.
Towards a framework for the quantitative assessment of trawling impact on the seabed and benthic ecosystem
Authors: Rijnsdorp A. D. , Bastardie F. , Bolam S. G. , Buhl-Mortensen L. , Eigaard O. R. , Hamon K. G. , Hiddink J. G. , Hintzen N. T. , Ivanović A. , Kenny A. , Laffargue P. , Nielsen J. R. , O'Neill F. G. , Piet G. J. , Polet H. , Sala A. , Smith C. , van Denderen P. D. , van Kooten T. , Zengin M.
Published: November 2015

A framework to assess the impact of mobile fishing gear on the seabed and benthic ecosystem is presented. The framework that can be used at regional and local scales provides indicators for both trawling pressure and ecological impact. It builds on high-resolution maps of trawling intensity and considers the physical effects of trawl gears on the seabed, on marine taxa, and on the functioning of the benthic ecosystem. Within the framework, a reductionist approach is applied that breaks down a fishing gear into its components, and a number of biological traits are chosen to determine either the vulnerability of the benthos to the impact of that gear component, or to provide a proxy for their ecological role. The approach considers gear elements, such as otter boards, twin trawl clump, and groundrope, and sweeps that herd the fish. The physical impact of these elements on the seabed, comprising scraping of the seabed, sediment mobilization, and penetration, is a function of the mass, size, and speed of the individual component. The impact of the elements on the benthic community is quantified using a biological-trait approach that considers the vulnerability of the benthic community to trawl impact (e.g. sediment position, morphology), the recovery rate (e.g. longevity, maturation age, reproductive characteristics, dispersal), and their ecological role. The framework is explored to compare the indicators for pressure and ecological impact of bottom trawling in three main seabed habitat types in the North Sea. Preliminary results show that the Sublittoral mud (EUNIS A5.3) is affected the most due to the combined effect of intensive fishing and large proportions of long-lived taxa.
Variation in Polyphenols, Tocols, γ‐Aminobutyric Acid, and Antioxidant Properties in Whole Grain Rice (Oryza sativa L.) as Affected by Different Germination Time
Authors: Wang Yan , Li Mei , Xu Feifei , Chai Lihong , Bao Jinsong , Shen Shengquan
Published: November 2015

Dynamic alterations in the polyphenols, tocols, antioxidant activities (AOA), and γ‐aminobutyric acid (GABA) contents of white, red, and black germinated rice upon different germination periods were studied. The results indicated that the contents of the free, bound, and total phenolics and AOA steadily increased during germination, even though the free part of colored germinated brown rice (GBR) showed a notable decline at the earlier stages, but still higher than the white rice. The compositions of the nine phenolic acids and six tocols generally accumulated in a time‐ and variety‐dependent manner during the germination process. However, the contents of p‐coumaric, ferulic, and sinapic acids displayed a pronounced increase with the duration of germination in all cultivars. The GABA in white, red, and black GBR accumulated to the highest content at the end of germination, which was 4.7, 14.2, and 6.7‐fold of their respective nongerminated counterparts. Interestingly, the total anthocyanin content in black GBR displayed a constant drop at earlier stages and then a rise at the later stages. These results suggest that prolonged germination may further increase the functional properties of GBR.
Prevalence of Streptomycin-Resistant Erwinia amylovora in New York Apple Orchards
Authors: Tancos K. A. , Villani S. , Kuehne S. , Borejsza-Wysocka E. , Breth D. , Carol J. , Aldwinckle H. S. , Cox K. D.
Published: November 2015

Resistance to streptomycin in Erwinia amylovora was first observed in the United States in the 1970s but was not found in New York until 2002, when streptomycin-resistant (SmR) E. amylovora was isolated from orchards in Wayne County. From 2011 to 2014, in total, 591 fire blight samples representing shoot blight, blossom blight, and rootstock blight were collected from 80 apple orchards in New York. From these samples, 1,280 isolates of E. amylovora were obtained and assessed for streptomycin resistance. In all, 34 SmR E. amylovora isolates were obtained from 19 individual commercial orchards. The majority of the resistant isolates were collected from orchards in Wayne County, and the remaining were from other counties in western New York. Of the 34 resistant isolates, 32 contained the streptomycin resistance gene pair strA/strB in the transposon Tn5393 on the nonconjugative plasmid pEA29. This determinant of streptomycin resistance has only been found in SmR E. amylovora isolates from Michigan and the SmR E. amylovora isolates discovered in Wayne County, NY in 2002. Currently, our data indicate that SmR E. amylovora is restricted to counties in western New York and is concentrated in the county with the original outbreak. Because the resistance is primarily present on the nonconjugative plasmid, it is possible that SmR has been present in Wayne County since the introduction in 2002, and has spread within and out of Wayne County to additional commercial growers over the past decade. However, research is still needed to provide in-depth understanding of the origin and spread of the newly discovered SmR E. amylovora to reduce the spread of streptomycin resistance into other apple-growing regions, and address the sustainability of streptomycin use for fire blight management in New York.
Identification and Characterization of New ‘CandidatusPhytoplasma solani’ Strains Associated with Bois Noir Disease inVitis viniferaL. Cultivars Showing a Range of Symptom Severity in Georgia, the Caucasus Region
Authors: Quaglino Fabio , Maghradze David , Casati Paola , Chkhaidze Nona , Lobjanidze Mzagho , Ravasio Adriano , Passera Alessandro , Venturini Giovanni , Failla Osvaldo , Bianco Piero Attilio
Published: November 2015

Evidence from a preliminary survey highlighted that ‘Candidatus Phytoplasma solani’, the etiological agent of bois noir (BN) disease of grapevine, infects grapevine varieties in Georgia, a country of the South Caucasus. In this study, field surveys were carried out to investigate the BN symptom severity in international and Georgian native varieties. ‘Ca. P. solani’ was detected and identified by polymerase chain reaction-based amplification and restriction fragment length polymorphism analysis of 16S ribosomal DNA, and further characterized by multiple gene typing analysis (vmp1 and stamp genes). Obtained data highlighted that the majority of Georgian grapevine varieties showed moderate and mild symptoms, whereas international cultivars exhibited severe symptoms. Molecular characterization of ‘Ca. P. solani’ from grapevine revealed the presence of 11 distinct phytoplasma types. Only one type (VmGe12/StGe7) was identical to a strain previously reported in periwinkle from Lebanon; the other ‘Ca. P. solani’ types are described here for the first time. Phylogenetic analyses of vmp1 and stamp gene concatenated nucleotide sequences showed that ‘Ca. P. solani’ strains in Georgia are associated mainly with the bindweed-related BN host system. Moreover, the fact that ‘Ca. P. solani’ strains are distributed in grapevine cultivars showing a range of symptom intensity suggests a different susceptibility of such local cultivars to BN.
Inheritance and Identification of a Major Quantitative Trait Locus (QTL) that Confers Resistance to Meloidogyne incognita and a Novel QTL for Plant Height in Sweet Sorghum
Authors: Harris-Shultz Karen R. , Davis Richard F. , Knoll Joseph E. , Anderson William , Wang Hongliang
Published: November 2015

Southern root-knot nematodes (Meloidogyne incognita) are a pest on many economically important row crop and vegetable species and management relies on chemicals, plant resistance, and cultural practices such as crop rotation. Little is known about the inheritance of resistance to M. incognita or the genomic regions associated with resistance in sorghum (Sorghum bicolor). In this study, an F2 population (n = 130) was developed between the resistant sweet sorghum cultivar ‘Honey Drip’ and the susceptible sweet cultivar ‘Collier’. Each F2 plant was phenotyped for stalk weight, height, juice Brix, root weight, total eggs, and eggs per gram of root. Strong correlations were observed between eggs per gram of root and total eggs, height and stalk weight, and between two measurements of Brix. Genotyping-by-sequencing was used to generate single nucleotide polymorphism markers. The G-Model, single marker analysis, interval mapping, and composite interval mapping were used to identify a major quantitative trait locus (QTL) on chromosome 3 for total eggs and eggs per gram of root. Furthermore, a new QTL for plant height was also discovered on chromosome 3. Simple sequence repeat markers were developed in the total eggs and eggs per gram of root QTL region and the markers flanking the resistance gene are 4.7 and 2.4 cM away. These markers can be utilized to move the southern root-knot nematode resistance gene from Honey Drip to any sorghum line.
Dexmedetomidine versus Propofol Sedation Reduces Delirium after Cardiac Surgery
Authors: Djaiani George , Silverton Natalie , Fedorko Ludwik , Carroll Jo , Styra Rima , Rao Vivek , Katznelson Rita
Published: November 2015

AbstractAbstract

When compared with propofol, dexmedetomidine sedation reduced incidence, delayed onset, and shortened duration of postoperative delirium in elderly patients after cardiac surgery.

Background

Postoperative delirium (POD) is a serious complication after cardiac surgery. Use of dexmedetomidine to prevent delirium is controversial. The authors hypothesized that dexmedetomidine sedation after cardiac surgery would reduce the incidence of POD.

Methods

After institutional ethics review board approval, and informed consent, a single-blinded, prospective, randomized controlled trial was conducted in patients 60 yr or older undergoing cardiac surgery. Patients with a history of serious mental illness, delirium, and severe dementia were excluded. Upon admission to intensive care unit (ICU), patients received either dexmedetomidine (0.4 μg/kg bolus followed by 0.2 to 0.7 μg kg−1 h−1 infusion) or propofol (25 to 50 μg kg−1 min−1 infusion) according to a computer-generated randomization code in blocks of four. Assessment of delirium was performed with confusion assessment method for ICU or confusion assessment method after discharge from ICU at 12-h intervals during the 5 postoperative days. Primary outcome was the incidence of POD.

Results

POD was present in 16 of 91 (17.5%) and 29 of 92 (31.5%) patients in dexmedetomidine and propofol groups, respectively (odds ratio, 0.46; 95% CI, 0.23 to 0.92; P = 0.028). Median onset of POD was on postoperative day 2 (1 to 4 days) versus 1 (1 to 4 days), P = 0.027, and duration of POD 2 days (1 to 4 days) versus 3 days (1 to 5 days), P = 0.04, in dexmedetomidine and propofol groups, respectively.

Conclusions

When compared with propofol, dexmedetomidine sedation reduced incidence, delayed onset, and shortened duration of POD in elderly patients after cardiac surgery. The absolute risk reduction for POD was 14%, with a number needed to treat of 7.1.
Endovascular Abdominal Aortic Aneurysm Repair through a Persistent Sciatic Artery
Authors: Ramanathan Rajesh , DesChamplain Michelle L. , Brinster Derek R.
Published: November 2015

Conventional access for endovascular infrarenal aortic aneurysm repair is through the femoral artery. In rare circumstances, an anomalous persistent sciatic artery may replace the femoral arterial system as the main blood supply of the lower extremity. We report the case of a 64-year-old woman with a rapidly expanding infrarenal abdominal aortic aneurysm. Preoperative computed tomography revealed a right persistent sciatic artery with an ipsilateral atrophic femoral artery. Her aortic aneurysm was successfully repaired using an endovascular approach with access through the right persistent sciatic artery and contralateral femoral artery. A persistent sciatic artery can be used as an access for endovascular treatment of an infrarenal aortic aneurysm. This technique can be extrapolated to the treatment of distal or contralateral aneurysms, precluding the need for open operation.
Combined Mitral and Tricuspid Valve Surgery Performed via a Right Minithoracotomy Approach
Authors: Mihos Christos G. , Pineda Andrés M. , Davila Hector , Larrauri-Reyes Maiteder C. , Santana Orlando
Published: November 2015

Objective

Combined mitral and tricuspid valve surgery is associated with an increased perioperative morbidity and mortality. We evaluated the outcomes of a less invasive right minithoracotomy approach in patients undergoing primary or reoperative double-valve surgery.

Methods

We retrospectively evaluated 132 consecutive patients with mitral and tricuspid valve disease who underwent double-valve surgery via a right minithoracotomy at our institution between January 2009 and April 2014.

Results

The cohort included 81 female (61%) and 51 male (39%) patients, with a mean ± SD age of 67 ± 13 years. The mean ± SD preoperative left ventricular ejection fraction, mitral regurgitation grade, and creatinine were 53% ± 12%, 3.8 ± 0.6, and 1.26 ± 1.17, respectively. The patients underwent primary (88%) or reoperative (12%) mitral and tricuspid valve surgery, which consisted of 88 mitral repairs (67%), 44 mitral replacements (33%), 131 tricuspid repairs (99%), and 1 tricuspid replacement (1%). Postoperatively, there were 6 cases of acute kidney injury (5%), 6 reoperations for bleeding (5%), 4 cerebrovascular accidents (3%), and 12 cases of atrial fibrillation (9%). The median intensive care unit length of stay and total hospital lengths of stay were 61 hours (interquartile range, 43–112 hours) and 8 days (interquartile range, 6–13 days), respectively. The in-hospital mortality was 4%. Actuarial survival at 1 and 5 years was 93% and 88%, respectively.

Conclusions

In patients undergoing primary or reoperative mitral and tricuspid valve surgery, a right minithoracotomy approach is associated with a low perioperative morbidity and good midterm survival.
Aortic Annulus Stabilization Technique for Rapid Deployment Aortic Valve Replacement
Authors: Ferrari Enrico , Siniscalchi Giuseppe , Tozzi Piergiorgio , von Segesser Ludwig
Published: November 2015

Rapid deployment aortic valve replacement (RDAVR) with the use of rapid deployment valve systems represents a smart alternative to the use of standard aortic bioprosthesis for aortic valve replacement. Nevertheless, its use is still debatable in patients with pure aortic valve regurgitation or true bicuspid aortic valve because of the risk of postoperative paravalvular leak. To address this issue, an optimal annulus-valve size match seems to be the ideal surgical strategy. This article describes a new technique developed to stabilize the aortic annulus and prevent paravalvular leak after RDAVR. To confirm the feasibility, this technique was performed in six patients with severe symptomatic aortic stenosis who were scheduled to undergo aortic valve replacement at our center. All patients survived surgery and were discharged from the hospital. There were no new intracardiac conduction system disturbances observed, and a permanent pacemaker implantation was not required in any of the patients. The intraoperative and postoperative echocardiogram confirmed successful positioning of the valve, and no paravalvular leak was observed. In this preliminary experience, RDAVR through a full sternotomy or an upper hemisternotomy approach with the use of aortic annulus stabilization technique was safe, and no leak was observed. Future studies on large series of patients are necessary to confirm the safety and effectiveness of this technique in preventing paravalvular leak in patients with true bicuspid aortic valves or pure aortic regurgitation.
Minimally Invasive Mitral Valve Surgery in Truly High-Risk Patients: Are We Pushing the Boundaries? An Observational Study
Authors: Moscarelli Marco , Margaryan Rafik , Cerillo Alfredo , Kallushi Enkel , Farneti Pierandrea , Solinas Marco
Published: November 2015

Objective

This study aimed to assess in a retrospective series of truly high-risk patients who underwent minimally invasive mitral valve surgery: (1) postoperative and long-term results and (2) logistic EuroSCORE and EuroSCORE II discrimination power.

Methods

Between 2003 and 2013, we reviewed in our institution patients who underwent minimally invasive mitral valve surgery with or without tricuspid valve repair via right minithoracotomy with logistic EuroSCORE of 20 or higher.

Results

Among a total number of 1604, 88 patients were identified. Median logistic and EuroSCORE II was 27.29 (interquartile range, 15.3) and 12.7% (11.3%), respectively. Mean (SD) age was 71.9 (8.4) years; 42 were female (47.7%); 60 patients (68.1%) underwent previous sternotomy. Mitral valve was replaced in 59 (67%) and repaired in 29 (32.9%) patients; tricuspid valve repair was performed in 23 patients (26.1%). Median cardiopulmonary bypass and cross-clamp times were 157 minutes (interquartile range, 131–187 minutes) and 83 minutes (81–116 minutes), respectively; conversion to sternotomy and reopening for bleeding was necessary in 4 (4.5%) and 3 (3.4%) patients; permanent and transient neurological injuries were reported in 6 (6.8%) and 3 (3.4%) patients; acute kidney injury was reported in 13 patients (14.7%); 15 patients (17%) had pulmonary complications. Ten patients died while in the hospital (11.2%). Survival at 6 years was 78% (95% confidence interval, 69–88).

Conclusions

In this series of truly high-risk patients, minimally invasive mitral surgery was associated with acceptable early mortality and morbidity as well as long-term outcomes; both logistic and EuroSCORE II showed suboptimal discrimination power.
Simulated Prosthesis Overlay for Patient-Specific Planning of Transcatheter Aortic Valve Implantation Procedures
Authors: Sündermann Simon H. , Gessat Michael , Maier Willibald , Kempfert Jörg , Frauenfelder Thomas , Nguyen Thi D. L. , Maisano Francesco , Falk Volkmar
Published: November 2015

Objective

We tested the hypothesis that simulated three-dimensional prosthesis overlay procedure planning may support valve selection in transcatheter aortic valve implantation (TAVI) procedures.

Methods

Preoperative multidimensional computed tomography (MDCT) data sets from 81 consecutive TAVI patients were included in the study. A planning tool was developed, which semiautomatically creates a three-dimensional model of the aortic root from these data. Three-dimensional templates of the commonly used TAVI implants are spatially registered with the patient data and presented as graphic overlay. Fourteen physicians used the tool to perform retrospective planning of TAVI procedures. Results of prosthesis sizing were compared with the prosthesis size used in the actually performed procedure, and the patients were accordingly divided into three groups: those with equal size (concordance with retrospective planning), oversizing (retrospective planning of a smaller prosthesis), and undersizing (retrospective planning of a larger prosthesis).

Results

In the oversizing group, 85% of the patients had new pacemaker implantation. In the undersizing group, in 66%, at least mild paravalvular leakage was observed (greater than grade 1 in one third of the cases). In 46% of the patients in the equal-size group, neither of these complications was observed.

Conclusions

Three-dimensional prosthesis overlay in MDCT-derived patient data for patient-specific planning of TAVI procedures is feasible. It may improve valve selection compared with two-dimensional MDCT planning and thus yield better outcomes.
Retained Blood Syndrome after Cardiac Surgery: A New Look at an Old Problem
Authors: Boyle Edward M. , Gillinov A. Marc , Cohn William E. , Ley S. Jill , Fischlein Theodor , Perrault Louis P.
Published: November 2015

Retained blood occurs when drainage systems fail to adequately evacuate blood during recovery from cardiothoracic surgery. As a result, a spectrum of mechanical and inflammatory complications can ensue in the acute, subacute, and chronic setting. The objectives of this review were to define the clinical syndrome associated with retained blood over the spectrum of recovery and to review existing literature regarding how this may lead to complications and contributes to poor outcomes. To better understand and prevent this constellation of clinical complications, a literature review was conducted, which led us to create a new label that better defines the clinical entity we have titled retained blood syndrome. Analysis of published reports revealed that 13.8% to 22.7% of cardiac surgical patients develop one or more components of retained blood syndrome. This can present in the acute, subacute, or chronic setting, with different pathophysiologic mechanisms active at different times. The development of retained blood syndrome has been linked to other clinical outcomes, including the development of postoperative atrial fibrillation and infection and the need for hospital readmission. Grouping multiple objectively measurable and potentially preventable postoperative complications that share a common etiology of retained blood over the continuum of recovery demonstrates a high prevalence of retained blood syndrome. This suggests the need to develop, implement, and test clinical strategies to enhance surgical drainage and reduce postoperative complications in patients undergoing cardiothoracic surgery.
Importance of Full-Length Scan of Arterial Grafts in Coronary Artery Bypass Grafting
Authors: Banjanović Bedrudin , Bergsland Jacob , Mujanović Emir , Kabil Emir
Published: November 2015

Cardiac ischemia after coronary artery bypass grafting is often caused by graft occlusion. Short- and long-term graft patency is related to the quality of the surgical technique during harvesting and anastomosis. Transit time flow measurement is a recognized technique for the quality control of grafts but may not rule out structural abnormalities in the conduits, which can cause graft occlusion. This article reports on two cases of suspected intra-arterial dissection of the left internal mammary artery despite satisfactory flow measurements. Routine ultrasound scanning of arterial conduits is helpful in distinguishing dissection and hematoma in the graft conduits.
Rare Presentation of Lupus Myocarditis With Acute Heart Failure—A Case Report
Authors: Malhotra Gurveen , Chua Serafin , Kodumuri Vamsi , Sivaraman Sivashankar , Ramdass Priya
Published: November 2015

Systemic lupus erythematosus is an autoimmune disease with diffuse organ involvement. The cardiac complications include pericarditis, myocarditis, pulmonary hypertension, coronary vasculitis, and Libman–Sacks endocarditis. Symptomatic lupus myocarditis presenting with left ventricular dysfunction, acute heart failure, and pulmonary edema, although rare, is a life-threatening complication. We report the occurrence of acute lupus myocarditis in a 38-year-old postpartum female who had a cesarean section a week before presentation for preeclampsia. Initially she was managed for pneumonia but later found to have acute pericarditis and myocarditis related to systemic lupus erythematosus. She had a complicated hospital course including acute respiratory failure and cardiogenic shock. She was started on pulse dose steroids besides the treatment for heart failure and had a dramatic improvement within days.
Immunohistochemistry Biomarkers in Nonmuscle Invasive Bladder Cancer
Authors: Ranzi Alana D. , da Silva Jéssica N.L. , Graziottin Túlio M. , Annels Nicola , Bica Claudia G.
Published: November 2015

Bladder cancer (BCa) is the most frequent urinary tract neoplasm. BCa results in significant mortality when the disease presents as muscle invasive. Around 75% to 80% of patients present with nonmuscle invasive bladder cancer (NMIBC), but recurrence and progression are significant issues, compelling current guidelines to recommend long-term surveillance. There is therefore an urgent and unmet need to identify and validate accurate biomarkers for the detection of disease recurrence to improve quality of life for the patients and reduce costs for health care providers, while maintaining or improving current outcomes. In this review, 38 publications on immunohistochemistry prognostic biomarkers, that were studied may be related in nonmuscle invasive bladder cancer, have been analyzed. The studies were organized according to the evaluated marker and their findings. It was demonstrated that the combination of independent complementary biomarkers could allow a more accurate prognosis than an isolated marker. Biomarkers, including p53, Ki-67, and CK20, with classic and prognostic factors with recurrence and novel markers such as EN2 may provide a more accurate prediction of outcome compared with any single marker, improving risk stratification and clinical management of patients with BCa.
MicroRNA-192-5p Promote the Proliferation and Metastasis of Hepatocellular Carcinoma Cell by Targeting SEMA3A
Authors: Yan-Chun Li , Hong-Mei Yi , Zhi-Hong Chen , Qing Hu , Yan-Hong Zhou , Ji-Fang Wen
Published: November 2015

Side population (SP) cells are a small subset of cells isolated from a cultured cancer cell line with characteristics similar to those of cancer stem cells, such as high metastatic and tumorigenic potentials. However, the molecular mechanisms remain unclear for the malignant properties of SP cells. In this study, SP cells were isolated by staining cultured HCCLM3 cells with fluorescent DNA-binding dye Hoechst 33342 and sorted by flow cytometry. The proportion of SP cells was 2.79%±0.19% in the HCCLM3 cell line. Compared with non-SP cells, SP cells possessed stronger capability of sphere formation and tumorigenicity, and expressed higher levels of CD133 and CD90. Then, we found that SP cells possessed 25 upregulated and 34 downregulated microRNAs with differences of >3-fold. As one of the upregulated microRNAs, miR-192-5p was computationally predicted to target semaphorin 3A (SEMA3A), a potent suppressor of tumor angiogenesis in various cancer models. Luciferase reporter assay showed that SEMA3A was a direct target of miR-192-5p. Overexpression of miR-192-5p promoted cell proliferation and metastasis targeting SEMA3A in HCCLM3 cells. Immunohistochemical staining revealed that SEMA3A expression was significantly reverse associated with metastasis in hepatocellular carcinoma tissues. The results indicate that miR-192-5p contributes to targeting SEMA3A in HCCLM3 cells, and this may be used as a target in targeted therapy and a marker for cancer behavior and prognosis.
Electrochemistry in supercritical fluids
Authors: Branch Jack A. , Bartlett Philip N.
Published: November 2015

A wide range of supercritical fluids (SCFs) have been studied as solvents for electrochemistry with carbon dioxide and hydrofluorocarbons (HFCs) being the most extensively studied. Recent advances have shown that it is possible to get well-resolved voltammetry in SCFs by suitable choice of the conditions and the electrolyte. In this review, we discuss the voltammetry obtained in these systems, studies of the double-layer capacitance, work on the electrodeposition of metals into high aspect ratio nanopores and the use of metallocenes as redox probes and standards in both supercritical carbon dioxide–acetonitrile and supercritical HFCs.
Supercritical carbon dioxide design strategies: from drug carriers to soft killers
Authors: Aguiar-Ricardo Ana , Bonifácio Vasco D. B. , Casimiro Teresa , Correia Vanessa G.
Published: November 2015

The integrated use of supercritical carbon dioxide (scCO
2
) and micro- and nanotechnologies has enabled new sustainable strategies for the manufacturing of new medications. ‘Green’ scCO
2
-based methodologies are well suited to improve either the synthesis or materials processing leading to the assembly of three-dimensional multifunctional constructs. By using scCO
2
either as C1 feedstock or as solvent, simple, economic, efficient and clean routes can be designed to synthesize materials with unique properties such as polyurea dendrimers and oxazoline-based polymers/oligomers. These new biocompatible, biodegradable and water-soluble polymeric materials can be engineered into multifunctional constructs with antimicrobial activity, targeting moieties, labelling units and/or efficiently loaded with therapeutics. This mini-review highlights the particular features exhibited by these materials resulting directly from the followed supercritical routes.
Kaiju: Fast and sensitive taxonomic classification for metagenomics
Authors: Menzel Peter , Lee Ng Kim , Krogh Anders
Published: November 2015

The constantly decreasing cost and increasing out-put of current sequencing technologies enable large scale metagenomic studies of microbial communities from diverse habitats. Therefore, fast and accurate methods for taxonomic classification are needed, which can operate on increasingly larger datasets and reference databases. Recently, several fast metagenomic classifiers have been developed, which are based on comparison of genomick-mers. However, nucleotide comparison using a fixedk-mer length often lacks the sensitivity to overcome the evolutionary distance between sampled species and genomes in the reference database. Here, we present the novel metagenome classifierKaijufor fast assignment of reads to taxa. Kaiju finds maximum exact matches on the protein-level using the Borrows-Wheeler transform, and can optionally allow amino acid substitutions in the search using a greedy heuristic. We show in a genome exclusion study that Kaiju can classify more reads with higher sensitivity and similar precision compared to fastk-mer based classifiers, especially in genera that are underrepresented in reference databases. We also demonstrate that Kaiju classifies more than twice as many reads in ten real metagenomes compared to programs based on genomick-mers. Kaiju can process up to millions of reads per minute, and its memory footprint is below 6 GB of RAM, allowing the analysis on a standard PC. The program is available under the GPL3 license at:http://bioinformatics-centre.github.io/kaiju
Strong Selection is Necessary for Evolution of Blindness in Cave Dwellers
Authors: Cartwright Reed A. , Schwartz Rachel S. , Merry Alexandra L. , Howell Megan M.
Published: November 2015

Blindness has evolved repeatedly in cave-dwelling organisms, and investigating the loss of sight in cave dwellers presents an opportunity to understand the operation of fundamental evolutionary processes, including drift, selection, mutation, and migration. The observation of blind organisms has prompted many hypotheses for their blindness, including both accumulation of neutral, loss-of-function mutations and adaptation to darkness. Here we model the evolution of blindness in caves. This model captures the interaction of three forces: (1) selection favoring alleles causing blindness, (2) immigration of sightedness alleles from a surface population, and (3) loss-of-function mutations creating blindness alleles. We investigated the dynamics of this model and determined selection-strength thresholds that result in blindness evolving in caves despite immigration of sightedness alleles from the surface. Our results indicate that strong selection is required for the evolution of blindness in cave-dwelling organisms, which is consistent with recent work suggesting a high metabolic cost of eye development.
Learning structure in gene expression data using deep architectures, with an application to gene clustering
Authors: Gupta Aman , Wang Haohan , Ganapathiraju Madhavi
Published: November 2015

Genes play a central role in all biological processes. DNA microarray technology has made it possible to study the expression behavior of thousands of genes in one go. Often, gene expression data is used to generate features for supervised and unsupervised learning tasks. At the same time, advances in the field of deep learning have made available a plethora of architectures. In this paper, we use deep architectures pre-trained in an unsupervised manner using denoising autoencoders as a preprocessing step for a popular unsupervised learning task. Denoising autoencoders (DA) can be used to learn a compact representation of input, and have been used to generate features for further supervised learning tasks. We propose that our deep architectures can be treated as empirical versions of Deep Belief Networks (DBNs). We use our deep architectures to regenerate gene expression time series data for two different data sets. We test our hypothesis on two popular datasets for the unsupervised learning task of clustering and find promising improvements in performance.
The Genetic Equidistance Phenomenon at the Proteomic Level
Authors: Luo Denghui , Huang Shi
Published: November 2015

The field of molecular evolution started with the alignment of a few protein sequences in the early 1960s. Among the first results found, the genetic equidistance result has turned out to be the most unexpected. It directly inspired the ad hoc universal molecular clock hypothesis that in turn inspired the neutral theory. Unfortunately, however, what is only a maximum distance phenomenon was mistakenly transformed into a mutation rate phenomenon and became known as such. Previous work studied a small set of selected proteins. We have performed proteome wide studies of 7 different sets of proteomes involving a total of 15 species. All 7 sets showed that within each set of 3 species the least complex species is approximately equidistant in average proteome wide identity to the two more complex ones. Thus, the genetic equidis-tance result is a universal phenomenon of maximum distance. There is a reality of constant albeit stepwise or discontinuous increase in complexity during evolution, the rate of which is what the original molecular clock hypothesis is really about. These results provide additional lines of evidence for the recently proposed maximum genetic diversity (MGD) hypothesis.

Availability and implementation

The source code repository is publicly available athttps://github.com/Sephiroth1st/EquidistanceScript

Contact

huangshi@sklmg.edu.cn

Supplementary information

Supplementary data are available online.
The State of Software in Evolutionary Biology
Authors: Darriba Diego , Flouri Tomáš , Stamatakis Alexandros
Published: November 2015

With Next Generation Sequencing Data (NGS) coming off age and being routinely used, evolutionary biology is transforming into a data-driven science.

As a consequence, researchers have to rely on a growing number of increasingly complex software. All widely used tools in our field have grown considerably, in terms of the number of features as well as lines of code. In addition, analysis pipelines now include substantially more components than 5-10 years ago.

A topic that has received little attention in this context is the code quality of widely used codes. Unfortunately, the majority of users tend to blindly trust software and the results it produces. To this end, we assessed the code quality of 15 highly cited tools (e.g., MrBayes, MAFFT, SweepFinder etc.) from the broader area of evolutionary biology that are used in current data analysis pipelines.

We also discuss widely unknown problems associated with floating point arithmetics for representing real numbers on computer systems. Since, the software quality of the tools we analyzed is rather mediocre, we provide a list of best practices for improving the quality of existing tools, but also list techniques that can be deployed for developing reliable, high quality scientific software from scratch.

Finally, we also discuss journal and science policy as well as funding issues that need to be addressed for improving software quality as well as ensuring support for developing new and maintaining existing software.

Our intention is to raise the awareness of the community regarding software quality issues and to emphasize the substantial lack of funding for scientific software development.
Towards a study of gene regulatory constraints to morphological evolution of theDrosophilaocellar region
Authors: Aguilar-Hidalgo D. , Becerra-Alonso D. , García-Morales D. , Casares F.
Published: November 2015

The morphology and function of organs depend on coordinated changes in gene expression during development. These changes are controlled by transcription factors, signaling pathways and their regulatory interactions, which are represented bygene regulatory networks(GRNs). Therefore, the structure of an organ GRN restricts the morphological and functionalvariationsthat the organ can experience –its potential morphospace. Therefore, two important questions arise when studying any GRN: what is the predicted available morphospace and what are the regulatory linkages that contribute the most to control morphological variation within this space. Here, we explore these questions by analyzing a small “3-node” GRN model that captures the Hh-driven regulatory interactions controlling a simple visual structure: the ocellar region ofDrosophila.Analysis of the model predicts that random variation of model parameters results in a specific non-random distribution of morphological variants. Study of a limited sample of Drosophilids and other dipterans finds a correspondence between the predicted phenotypic range and that found in nature. As an alternative to simulations, we apply Bayesian Networks methods in order to identify the set of parameters with the largest contribution to morphological variation. Our results predict the potential morphological space of the ocellar complex, and identify likely candidate processes to be responsible for ocellar morphological evolution using Bayesian networks. We further discuss the assumptions that the approach we have taken entails and their validity.
Expression, purification and crystallization of a plant polyketide cyclase fromCannabis sativa
Authors: Yang Xinmei , Matsui Takashi , Mori Takahiro , Taura Futoshi , Noguchi Hiroshi , Abe Ikuro , Morita Hiroyuki
Published: November 2015

Plant polyketides are a structurally diverse family of natural products. In the biosynthesis of plant polyketides, the construction of the carbocyclic scaffold is a key step in diversifying the polyketide structure. Olivetolic acid cyclase (OAC) fromCannabis sativaL. is the only known plant polyketide cyclase that catalyzes the C2–C7 intramolecular aldol cyclization of linear pentyl tetra-β-ketide-CoA to generate olivetolic acid in the biosynthesis of cannabinoids. The enzyme is also thought to belong to the dimeric α+β barrel (DABB) protein family. However, because of a lack of functional analysis of other plant DABB proteins and low sequence identity with the functionally distinct bacterial DABB proteins, the catalytic mechanism of OAC has remained unclear. To clarify the intimate catalytic mechanism of OAC, the enzyme was overexpressed inEscherichia coliand crystallized using the vapour-diffusion method. The crystals diffracted X-rays to 1.40 Å resolution and belonged to space groupP3121 orP3221, with unit-cell parametersa=b= 47.3,c= 176.0 Å. Further crystallographic analysis will provide valuable insights into the structure–function relationship and catalytic mechanism of OAC.
Crystal structure of tris(N-methylsalicylaldiminato-κ2N,O)vanadium(III)
Authors: Hilbert Jessica , Kabus Sven , Näther Christian , Bensch Wolfgang
Published: November 2015

The structure of the title complex, [V(C8H8NO)3], comprises neutral and discrete complexes, in which the VIIIcation is coordinated by three anionicN-methylalicylaldiminate ligands within a slightly distortedmer-N3O3octahedral geometry. In the crystal structure, the molecules are linkedviaC—H...O hydrogen bonds into supramolecular chains that extend along thecaxis.
The human side of economic development in Africa: a paradigm shift
Authors: Kuada John
Published: November 2015

Purpose

– This editorial builds on the distinction between soft and hard economics and discusses dominant explanations for the development challenges of Sub-Sahara African (SSA) countries. It also seeks to offer a backdrop for the papers in the present volume of AJEMS. The paper aims to discuss these issues.

Design/methodology/approach

– It is based on a review of a selection of literature that highlights the dominant perspectives in neoclassical economics and competing streams of research that provide alternative perspectives.

Findings

– The review suggests the emergence of a competing paradigm that focuses attention on the human factor in economic growth process – i.e. the development of human capability as a foundation of sustainable inclusive growth. The competing streams of research seem to co-exist today, but there are potentials for paradigmatic criss-crossing in future research.

Originality/value

– It provides directions for future research into issues of economic growth and poverty alleviation in SSA.
Social protection for poor, vulnerable and disadvantaged groups
Authors: Brzeska Joanna , Das Mousumi , Fan Shenggen
Published: November 2015

Purpose

– The purpose of this paper is to identify the pathways through which social protection policies in China and India can address the key challenges facing poor, vulnerable, and disadvantaged groups under rapid transformation in both countries.

Design/methodology/approach

– This paper reviews the main social protection policies in China and India and analyzes the challenges that they are facing. This analysis is based on an evaluation of poverty and food security trends in both countries among vulnerable and disadvantaged groups followed by an overview of major experiences and gaps in social protection policies in the two emerging Asian giants.

Findings

– Improving the coverage and targeting of social protection systems is vital, and will require a multi-faceted reform portfolio that promotes more integrated and horizontally equitable systems. Emphasis should be placed on developing productive, cross-sectoral social protection programs that combine short-term social safety support with long-term tools to enhance productivity, paying special attention to nutrition, health, and human capital development. More efficient coverage and targeting should bridge the rural and urban divide and be grounded in transparent criteria and procedures that govern program implementation at all levels of the government. As both countries become more urbanized, social protection programs need to give equal attention to emerging food insecurity and nutrition issues within urban areas without detracting from food security and nutrition efforts in rural areas.

Originality/value

– Faced with a sizable population of undernourished and poor people, India and China have applied rather different approaches to address food insecurity. The originality and value of this paper lie in an in-depth parallel analysis of how China and India can better use their social protection systems to address food insecurity and undernutrition among poor, vulnerable, and disadvantaged groups.