bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Atlantic salmon individuals with different outcomes of cardiomyopathy syndrome (CMS)
Authors: Timmerhaus Gerrit , Krasnov Aleksei , Takle Harald , Afanasyev Sergey , Nilsen Pål , Rode Marit , Jørgensen Sven Martin
Published: September 2012

Background

Cardiomyopathy syndrome (CMS) is a severe disease of Atlantic salmon (Salmo salar L.) associated with significant economic losses in the aquaculture industry. CMS is diagnosed with a severe inflammation and degradation of myocardial tissue caused by a double-stranded RNA virus named piscine myocarditis virus (PMCV), with structural similarities to the Totiviridae family. In the present study we characterized individual host responses and genomic determinants of different disease outcomes.

Results

From time course studies of experimentally infected Atlantic salmon post-smolts, fish exhibited different outcomes of infection and disease. High responder (HR) fish were characterized with sustained and increased viral load and pathology in heart tissue. Low responder (LR) fish showed declining viral load from 6–10 weeks post infection (wpi) and absence of pathology. Global gene expression (SIQ2.0 oligonucleotide microarray) in HR and LR hearts during infection was compared, in order to characterize differences in the host response and to identify genes with expression patterns that could explain or predict the different outcomes of disease. Virus-responsive genes involved in early antiviral and innate immune responses were upregulated equally in LR and HR at the first stage (2–4 wpi), reflecting the initial increase in virus replication. Repression of heart muscle development was identified by gene ontology enrichment analyses, indicating the early onset of pathology. By six weeks both responder groups had comparable viral load, while increased pathology was observed in HR fish. This was reflected by induced expression of genes implicated in apoptosis and cell death mechanisms, presumably related to lymphocyte regulation and survival. In contrast, LR fish showed earlier activation of NK cell-mediated cytotoxicity and NOD-like receptor signaling pathways. At the late stage of infection, increased pathology and viral load in HR was accompanied by a broad activation of genes involved in adaptive immunity and particularly T cell responses, probably reflecting the increased infiltration and homing of virus-specific T cells to the infected heart. This was in sharp contrast to LR fish, where recovery and reduced viral load was associated with a significantly reduced transcription of adaptive immunity genes and activation of genes involved in energy metabolism.

Conclusions

In contrast to LR, a stronger and sustained expression of genes involved in adaptive immune responses in heart tissue of HR at the late stage of disease probably reflected the increased lymphocyte infiltration and pathological outcome. In addition to controlled adaptive immunity and activation of genes involved in cardiac energy metabolism in LR at the late stage, recovery of this group could also be related to an earlier activation of NOD-like receptor signaling and NK cell-mediated cytotoxicity pathways.
Transcriptome of the adult female malaria mosquito vector Anopheles albimanus
Authors: Martínez-Barnetche Jesús , Gómez-Barreto Rosa E , Ovilla-Muñoz Marbella , Téllez-Sosa Juan , López David E García , Dinglasan Rhoel R , Mohien Ceereena Ubaida , MacCallum Robert M , Redmond Seth N , Gibbons John G , Rokas Antonis , Machado Carlos A , Cazares-Raga Febe E , González-Cerón Lilia , Hernández-Martínez Salvador , López Mario H Rodríguez
Published: September 2012

Background

Human Malaria is transmitted by mosquitoes of the genusAnopheles. Transmission is a complex phenomenon involving biological and environmental factors of humans, parasites and mosquitoes. Among more than 500 anopheline species, only a few species from different branches of the mosquito evolutionary tree transmit malaria, suggesting that their vectorial capacity has evolved independently.Anopheles albimanus(subgenusNyssorhynchus) is an important malaria vector in the Americas. The divergence time betweenAnopheles gambiae, the main malaria vector in Africa, and the Neotropical vectors has been estimated to be 100 My. To better understand the biological basis of malaria transmission and to develop novel and effective means of vector control, there is a need to explore the mosquito biology beyond theAn. gambiaecomplex.

Results

We sequenced the transcriptome of theAn. albimanusadult female. By combining Sanger, 454 and Illumina sequences from cDNA libraries derived from the midgut, cuticular fat body, dorsal vessel, salivary gland and whole body, we generated a single, high-quality assembly containing 16,669 transcripts, 92% of which mapped to theAn. darlingigenome and covered 90% of the core eukaryotic genome. Bidirectional comparisons between theAn. gambiae,An. darlingiandAn. albimanuspredicted proteomes allowed the identification of 3,772 putative orthologs. More than half of the transcripts had a match to proteins in other insect vectors and had an InterPro annotation. We identified several protein families that may be relevant to the study ofPlasmodium-mosquito interaction. An open source transcript annotation browser called GDAV (Genome-Delinked Annotation Viewer) was developed to facilitate public access to the data generated by this and future transcriptome projects.

Conclusions

We have explored the adult female transcriptome of one important New World malaria vector,An. albimanus.We identified protein-coding transcripts involved in biological processes that may be relevant to thePlasmodiumlifecycle and can serve as the starting point for searching targets for novel control strategies. Our data increase the available genomic information regardingAn. albimanusseveral hundred-fold, and will facilitate molecular research in medical entomology, evolutionary biology, genomics and proteomics of anopheline mosquito vectors. The data reported in this manuscript is accessible to the community via the VectorBase website (http://www.vectorbase.org/Other/AdditionalOrganisms/).
Identification of chemosensory receptor genes in Manduca sexta and knockdown by RNA interference
Authors: Howlett Natalie , Dauber Katherine L , Shukla Aditi , Morton Brian , Glendinning John I , Brent Elyssa , Gleason Caroline , Islam Fahmida , Izquierdo Denisse , Sanghavi Sweta , Afroz Anika , Aslam Aanam , Barbaro Marissa , Blutstein Rebekah , Borovka Margarita , Desire Brianna , Elikhis Ayala , Fan Qing , Hoffman Katherine , Huang Amy , Keefe Dominique , Lopatin Sarah , Miller Samara , Patel Priyata , Rizzini Danielle , Robinson Alyssa , Rokins Karimah , Turlik Aneta , Mansfield Jennifer H
Published: September 2012

Background

Insects detect environmental chemicals via a large and rapidly evolving family of chemosensory receptor proteins. Although our understanding of the molecular genetic basis for Drosophila chemoreception has increased enormously in the last decade, similar understanding in other insects remains limited. The tobacco hornworm, Manduca sexta, has long been an important model for insect chemosensation, particularly from ecological, behavioral, and physiological standpoints. It is also a major agricultural pest on solanaceous crops. However, little sequence information and lack of genetic tools has prevented molecular genetic analysis in this species. The ability to connect molecular genetic mechanisms, including potential lineage-specific changes in chemosensory genes, to ecologically relevant behaviors and specializations in M. sexta would be greatly beneficial.

Results

Here, we sequenced transcriptomes from adult and larval chemosensory tissues and identified chemosensory genes based on sequence homology. We also used dsRNA feeding as a method to induce RNA interference in larval chemosensory tissues.

Conclusions

We report identification of new chemosensory receptor genes including 17 novel odorant receptors and one novel gustatory receptor. Further, we demonstrate that systemic RNA interference can be used in larval olfactory neurons to reduce expression of chemosensory receptor transcripts. Together, our results further the development of M. sexta as a model for functional analysis of insect chemosensation.
Comparing frailty measures in their ability to predict adverse outcome among older residents of assisted living
Authors: Hogan David B , Freiheit Elizabeth A , Strain Laurel A , Patten Scott B , Schmaltz Heidi N , Rolfson Darryl , Maxwell Colleen J
Published: September 2012

Background

Few studies have directly compared the competing approaches to identifying frailty in more vulnerable older populations. We examined the ability of two versions of a frailty index (43 vs. 83 items), the Cardiovascular Health Study (CHS) frailty criteria, and the CHESS scale to accurately predict the occurrence of three outcomes among Assisted Living (AL) residents followed over one year.

Methods

The three frailty measures and the CHESS scale were derived from assessment items completed among 1,066 AL residents (aged 65+) participating in the Alberta Continuing Care Epidemiological Studies (ACCES). Adjusted risks of one-year mortality, hospitalization and long-term care placement were estimated for those categorized as frail or pre-frail compared with non-frail (or at high/intermediate vs. low risk on CHESS). The area under the ROC curve (AUC) was calculated for select models to assess the predictive accuracy of the different frailty measures and CHESS scale in relation to the three outcomes examined.

Results

Frail subjects defined by the three approaches and those at high risk for decline on CHESS showed a statistically significant increased risk for death and long-term care placement compared with those categorized as either not frail or at low risk for decline. The risk estimates for hospitalization associated with the frailty measures and CHESS were generally weaker with one of the frailty indices (43 items) showing no significant association. For death and long-term care placement, the addition of frailty (however derived) or CHESS significantly improved on the AUC obtained with a model including only age, sex and co-morbidity, though the magnitude of improvement was sometimes small. The different frailty/risk models did not differ significantly from each other in predicting mortality or hospitalization; however, one of the frailty indices (83 items) showed significantly better performance over the other measures in predicting long-term care placement.

Conclusions

Using different approaches, varying degrees of frailty were detected within the AL population. The various approaches to defining frailty were generally more similar than dissimilar with regard to predictive accuracy with some exceptions. The clinical implications and opportunities of detecting frailty in more vulnerable older adults require further investigation.
SDHA loss of function mutations in a subset of young adult wild-type gastrointestinal stromal tumors
Authors: Italiano Antoine , Chen Chun-Liang , Sung Yun-Shao , Singer Samuel , DeMatteo Ronald P , LaQuaglia Michael P , Besmer Peter , Socci Nicholas , Antonescu Cristina R
Published: September 2012

Background

A subset of KIT/PDGFRA wild-type gastrointestinal stromal tumors (WT GIST) have been associated with alteration of the succinate dehydrogenase (SDH) complex II function. A recent report identified four non-syndromic, KIT/PDGFRA WT GIST harboring compound heterozygous or homozygous mutations in SDHA encoding the main subunit of the SDH complex II.

Methods

Next generation sequencing was applied on five pediatric and one young adult WT GIST, by whole exome capture and SOLiD 3-plus system sequencing. The putative mutations were first confirmed by Sanger sequencing and then screened on a larger panel of 11 pediatric and young adult WT GIST, including 5 in the context of Carney triad.

Results

A germline p.Arg31X nonsense SDHA mutation was identified in one of the six cases tested by SOLiD platform. An additional p.D38V missense mutation in SDHA exon 2 was identified by Sanger sequencing in the extended KIT/PDGFRA WT GIST patients cohort. Western blotting showed loss of SDHA expression in the two cases harboring SDHA mutations, while expression being retained in the other WT GIST tumors. Results were further confirmed by immunohistochemistry for both SDHA and SDHB, which showed a concurrent loss of expression of both proteins in SDHA-mutant lesions, while the remaining WT tumors showed only loss of SDHB expression.

Conclusions

Germline and/or somatic aberrations of SDHA occur in a small subset of KIT/PDGFRA WT GISTs, outside the Carney’s triad and are associated with loss of both SDHA and SDHB protein expression. Mutations of the SDH complex II are more particularly associated with KIT/PDGFRA WT GIST occurring in young adults. Although pediatric GIST consistently display alterations of SDHB protein expression, further molecular studies are needed to identify the crucial genes involved in their tumorigenesis.
Efficacy of liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, on body weight, eating behavior, and glycemic control, in Japanese obese type 2 diabetes
Authors: Fujishima Yuya , Maeda Norikazu , Inoue Kana , Kashine Susumu , Nishizawa Hitoshi , Hirata Ayumu , Kozawa Junji , Yasuda Tetsuyuki , Okita Kohei , Imagawa Akihisa , Funahashi Tohru , Shimomura Iichiro
Published: September 2012

Background

We recently reported that short-term treatment with liraglutide (20.0 ± 6.4 days) reduced body weight and improved some scales of eating behavior in Japanese type 2 diabetes inpatients. However, it remained uncertain whether such liraglutide-induced improvement is maintained after discharge from the hospital. The aim of the present study was to determine the long-term effects of liraglutide on body weight, glycemic control, and eating behavior in Japanese obese type 2 diabetics.

Methods

Patients with obesity (body mass index (BMI) >25 kg/m2) and type 2 diabetes were hospitalized at Osaka University Hospital between November 2010 and December 2011. BMI and glycated hemoglobin (HbA1c) were examined on admission, at discharge and at 1, 3, and 6 months after discharge. For the liraglutide group (BMI; 31.3 ± 5.3 kg/m2, n = 29), patients were introduced to liraglutide after correction of hyperglycemic by insulin or oral glucose-lowering drugs and maintained on liraglutide after discharge. Eating behavior was assessed in patients treated with liraglutide using The Guideline For Obesity questionnaire issued by the Japan Society for the Study of Obesity, at admission, discharge, 3 and 6 months after discharge. For the insulin group (BMI; 29.1 ± 3.0 kg/m2, n = 28), each patient was treated with insulin during hospitalization and glycemic control maintained by insulin after discharge.

Results

Liraglutide induced significant and persistent weight loss from admission up to 6 months after discharge, while no change in body weight after discharge was noted in the insulin group. Liraglutide produced significant improvements in all major scores of eating behavior questionnaire items and such effect was maintained at 6 months after discharge. Weight loss correlated significantly with the decrease in scores for recognition of weight and constitution, sense of hunger, and eating style.

Conclusion

Liraglutide produced meaningful long-term weight loss and significantly improved eating behavior in obese Japanese patients with type 2 diabetes.
Cystatin C and asymptomatic coronary artery disease in patients with metabolic syndrome and normal glomerular filtration rate
Authors: Qing Xie , Furong Wang , Yunxia Liu , Jian Zhang , Xuping Wang , Ling Gao
Published: September 2012

Background

All of the components of Metabolic syndrome (MetS) have been regarded as risk factors for coronary artery disease (CAD). Early detection of CAD in asymptomatic patients with MetS remains a challenge. Cystatin C,which has been proposed as a novel marker of renal dysfunction,is correlated with mortality in CAD, The purpose of the study was to evaluate whether cystatin C is a potential marker of asymptomatic CAD in MetS patients with normal kidney function.

Methods

A total of 211asymptomatic MetS patients without prior history of CAD patients were included in a cross-sectional study. Patients were divided into MetS with asymptomatic CAD (n = 136) and MetS without CAD (n = 75) groups according to coronary angiograph results. Serum cystatin C levels were measured using particle enhanced immunonephelometric assays. We first assessed whether there is an independent association of cystatin C with the presence and severity of asymptomatic CAD. Then, we investigated the association between cystatin C and other biochemical risk factors for atherosclerosis.

Results

Serum cystatin C levels in patients with asymptomatic CAD were significantly higher than those without CAD (P = 0.004). A multiple logistic regression analysis demonstrated cystatin C was independently associated with the presence of asymptomatic CAD (OR = 1.326, 95%CI: 1.086-1.619). On receiver operating characteristics (ROC) analysis, the area under the curve (AUC) was 0.622 (95 % CI: 0543–0.701, P = 0.003), and cystatin C showed a moderate predictive value. Furthermore, cystatin C was independently correlated with Gensini score (standardized β = 0.183, P = 0.007), and serum cystatin C levels increased with the increasing of number of disease vessels (P = 0.005). In a multiple stepwise regression analysis, uric acid (UA)(P < 0.001), body mass index (BMI)(P = 0.002), triglyceride(TG)(P = 0.03), estimated glomerular filtration rate (eGFR)(P < 0.001), and fibrinogen(P = 0.001) were independently associated with cystatin C.

Conclusions

Serum cystatin C in our study was significantly associated with the presence and severity of asymptomatic CAD in MetS patients with normal kidney function, suggesting that cystatin C is probably more than a marker of glomerular filtration rate.
From intervention to impact: modelling the potential mortality impact achievable by different long-lasting, insecticide-treated net delivery strategies
Authors: Okell Lucy C , Paintain Lucy Smith , Webster Jayne , Hanson Kara , Lines Jo
Published: September 2012

Background

The current target of universal access to long-lasting, insecticide-treated nets (LLIN) is 80% coverage to reduce malaria deaths by 75% by 2015. So far, campaigns have been the main channel for large-scale delivery of LLINs, however the World Health Organization has recommended that equal priority should be given to delivery via routine antenatal care (ANC) and immunization systems (EPI) to target pregnant women and children from birth. These various channels of LLIN delivery are targeted to children of different ages. Since risk of mortality varies with child age and LLIN effectiveness declines with net age, it was hypothesized that the age at which a child receives a new LLIN, and therefore the delivery channel, is important in optimizing the health impact of a net.

Methods

A simple dynamic mathematical model was developed of delivery and impact of LLINs among children under five years of age and their household members, incorporating data on age-specific malaria death rates, net use by household structure, and net efficacy over time.

Results

The presented analysis finds that supplementing a universal mass campaign with extra ANC delivery would achieve a 1.4 times higher mortality reduction than campaign delivery alone, reflecting that children born in the years between campaigns would otherwise have access to old nets or no nets at an age of high risk. The relative advantage of supplementary ANC delivery is still present though smaller if malaria transmission levels are lower or if there is a strong mass effect achieved by mass campaigns.

Conclusion

These results indicate that LLIN delivery policies must take into account the age of greatest malaria risk. Emphasis should be placed on supporting routine delivery of LLINs to young children as well as campaigns.
Daily temperature and mortality: a study of distributed lag non-linear effect and effect modification in Guangzhou
Authors: Yang Jun , Ou Chun-Quan , Ding Yan , Zhou Ying-Xue , Chen Ping-Yan
Published: September 2012

Background

Although many studies have documented health effects of ambient temperature, little evidence is available in subtropical or tropical regions, and effect modifiers remain uncertain. We examined the effects of daily mean temperature on mortality and effect modification in the subtropical city of Guangzhou, China.

Methods

A Poisson regression model combined with distributed lag non-linear model was applied to assess the non-linear and lag patterns of the association between daily mean temperature and mortality from 2003 to 2007 in Guangzhou. The case-only approach was used to determine whether the effect of temperature was modified by individual characteristics, including sex, age, educational attainment and occupation class.

Results

Hot effect was immediate and limited to the first 5 days, with an overall increase of 15.46% (95% confidence interval: 10.05% to 20.87%) in mortality risk comparing the 99th and the 90th percentile temperature. Cold effect persisted for approximately 12 days, with a 20.39% (11.78% to 29.01%) increase in risk comparing the first and the 10th percentile temperature. The effects were especially remarkable for cardiovascular and respiratory mortality. The effects of both hot and cold temperatures were greater among the elderly. Females suffered more from hot-associated mortality than males. We also found significant effect modification by educational attainment and occupation class.

Conclusions

There are significant mortality effects of hot and cold temperatures in Guangzhou. The elderly, females and subjects with low socioeconomic status have been identified as especially vulnerable to the effect of ambient temperatures.
Cross-cultural adaptation of the CHO-KLAT for boys with hemophilia in rural and urban china
Authors: Wu Runhui , Zhang Jishui , Luke Koon Hung , Wu Xinyi , Burke Tricia , Tang Ling , Poon Man-Chiu , Li Xiaojing , Zhou Min , Sun Jing , Hang Marrisa , Blanchette Victor , Young Nancy L
Published: September 2012

Background

Quality of life (QoL) is increasingly recognized as an important outcome measure in clinical trials. The Canadian Hemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT) shows promise for use in China.

Objective

To adapt the CHO-KLAT version 2.0 for use in clinical trials in China.

Methods

Forward and back translations of the CHO-KLAT2.0 were completed in 2008. Between October 2009 and June 2010, a series of 3 focus groups were held with 20 boys and 31 parents in rural and urban China to elicit additional concepts, important to their QoL, for the Chinese CHO-KLAT2.0. All of the items identified by boys and parents were reviewed by a group of experts, resulting in a Chinese version of the CHO-KLAT2.0. This version underwent a detailed cognitive debriefing process between October 2010 and June 2011. Thirteen patient-parent pairs participated in this cognitive debriefing process until a stable and clearly understood Chinese version of the CHO-KLAT2.0 was obtained.

Results

The initial back translation of the Chinese CHO-KLAT2.0 was slightly discrepant from the original English version on 12 items. These were all successfully adjudicated. The focus groups identified 9 new items that formed an add-on Socio-Economic Context (SEC) module for China. Linguistic improvements were made after the 2nd, 5th, 7th and 13th cognitive debriefings pairs and affected a total of 18 items. The result was a 35 item CHO-KLAT2.0 and a SEC module in Simplified Chinese, both of which have good content validity.

Conclusion

This detailed process proved to be extremely valuable in ensuring the items were accurately interpreted by Chinese boys with hemophilia ages ≤18 years. The need for the additional SEC module highlighted the different context that currently exists in China with regard to hemophilia care as compared to many Western countries, and will be important in tracking progress within both rural and urban China over time. Changes based on the cognitive debriefings suggest that expert verbatim translation alone is not sufficient. The Chinese version of the CHO-KLAT2.0 is well understood by boys with hemophilia in China. Next steps will be to test its construct validity and reliability in boys with hemophilia in China.
Dynamics of microRNAs in bull spermatozoa
Authors: Govindaraju Aruna , Uzun Alper , Robertson LaShonda , Atli Mehmet O , Kaya Abdullah , Topper Einko , Crate Elizabeth A , Padbury James , Perkins Andy , Memili Erdogan
Published: September 2012

Background

MicroRNAs are small non-coding RNAs that regulate gene expression and thus play important roles in mammalian development. However, the comprehensive lists of microRNAs, as well as, molecular mechanisms by which microRNAs regulate gene expression during gamete and embryo development are poorly defined. The objectives of this study were to determine microRNAs in bull sperm and predict their functions.

Methods

To accomplish our objectives we isolated miRNAs from sperm of high and low fertility bulls, conducted microRNA microarray experiments and validated expression of a panel of microRNAs using real time RT-PCR. Bioinformatic approaches were carried out to identify regulated targets.

Results

We demonstrated that an abundance of microRNAs were present in bovine spermatozoa, however, only seven were differentially expressed; hsa-aga-3155, -8197, -6727, -11796, -14189, -6125, -13659. The abundance of miRNAs in the spermatozoa and the differential expression in sperm from high vs. low fertility bulls suggests that the miRNAs possibly play important functions in the regulating mechanisms of bovine spermatozoa.

Conclusion

Identification of specific microRNAs expressed in spermatozoa of bulls with different fertility phenotypes will help better understand mammalian gametogenesis and early development.
Evaluation of a multi-marker immunomagnetic enrichment assay for the quantification of circulating melanoma cells
Authors: Freeman James B , Gray Elin S , Millward Michael , Pearce Robert , Ziman Melanie
Published: September 2012

Background

Circulating melanoma cells (CMCs) are thought to be valuable in improving measures of prognosis in melanoma patients and may be a useful marker of residual disease to identify non-metastatic patients requiring adjuvant therapy. We investigated whether immunomagnetic enrichment targeting multiple markers allows more efficient enrichment of CMCs from patient peripheral blood than targeting a single marker. Furthermore, we aimed to determine whether the number of CMCs in patient blood was associated with disease stage.

Methods

We captured CMCs by targeting the melanoma associated markers MCSP and MCAM as well as the melanoma stem cell markers ABCB5 and CD271, both individually and in combination, by immunomagnetic enrichment. CMCs were enriched and quantified from the peripheral blood of 10 non-metastatic and 13 metastatic melanoma patients.

Results

Targeting all markers in combination resulted in the enrichment of more CMCs than when any individual marker was targeted (p < 0.001-0.028). Furthermore, when a combination of markers was targeted, a greater number of CMCs were enriched in metastatic patients compared with non-metastatic patients (p = 0.007).

Conclusions

Our results demonstrated that a combination of markers should be targeted for optimal isolation of CMCs. In addition, there are significantly more CMCs in metastatic patients compared with non-metastatic patients and therefore quantification of CMCs may prove to be a useful marker of disease progression.
The relationship between HBV serum markers and the clinicopathological characteristics of hepatitis B virus-associated glomerulonephritis (HBV-GN) in the northeastern chinese population
Authors: Zhang Lei , Meng Hongxue , Han Xingying , Han Changsong , Sun Chuanhui , Ye Fei , Jin Xiaoming
Published: September 2012

Background

To investigate the effect of HBV markers on HBV-GN.

Methods

The immunohistochemistry was used to detect HBsAg and HBcAg in frozen sections of renal biopsy, the changes in HBV serum markers, renal functional parameters and clinical manifestations or symptoms were observed to analyze renal damage.

Results

Using renal biopsy data from 329 cases, this study found that the most common pathological subtype in HBV-GN was mesangioproliferative glomerulonephritis (MsPGN) (24.9%, P <0.05), and 29.4% of patients who show serological HBsAg, HBeAg and anti-HBc positive developed membranoproliferative glomerulonephritis (MPGN) (P <0.05). The immunohistochemistry was used to detect HBsAg and HBcAg in frozen sections.50% of HBsAg and HBcAg deposits was observed in the glomeruli of MPGN patients, while 36.6% of HBsAg and 43.9% of HBcAg deposited in the glomeruli of MsPGN patients. The deposits of HBsAg and HBcAg in glomeruli were directly correlated with IgA, IgG, IgM and C3 deposits. In addition, cases with a moderate to severe decrease as reflected by the glomerular filtration rate (GFR) were predominantly patients with MPGN (31.6%, P <0.05) or MsPGN (21.1%, P <0.05). Patients who were serological HBsAg, HBeAg and anti-HBc positive or HBsAg, anti-HBe and anti-HBc positive mainly exhibited urine and renal parameter changes.

Conclusion

Examination of HBV markers in serum and renal biopsy will be useful for clinicians to predict the renal damage in early stage when it is reversible in HBV-GN.
Sea-Anemone Toxin ATX-II Elicits A-Fiber-Dependent Pain and Enhances Resurgent and Persistent Sodium Currents in Large Sensory Neurons
Authors: Klinger Alexandra B , Eberhardt Mirjam , Link Andrea S , Namer Barbara , Kutsche Lisa K , Schuy E Theresa , Sittl Ruth , Hoffmann Tali , Alzheimer Christian , Huth Tobias , Carr Richard W , Lampert Angelika
Published: September 2012

Background:

Gain-of-function mutations of the nociceptive voltage-gated sodium channel Nav1.7 lead to inherited pain syndromes, such as paroxysmal extreme pain disorder (PEPD). One characteristic of these mutations is slowed fast-inactivation kinetics, which may give rise to resurgent sodium currents. It is long known that toxins from Anemonia sulcata, such as ATX-II, slow fast inactivation and skin contact for example during diving leads to various symptoms such as pain and itch. Here, we investigated if ATX-II induces resurgent currents in sensory neurons of the dorsal root ganglion (DRGs) and how this may translate into human sensations.

Results:

In large A-fiber related DRGs ATX-II (5 nM) enhances persistent and resurgent sodium currents, but failed to do so in small C-fiber linked DRGs when investigated using the whole-cell patch-clamp technique. Resurgent currents are thought to depend on the presence of the sodium channel β4-subunit. Using RT-qPCR experiments, we show that small DRGs express significantly less β4 mRNA than large sensory neurons. With the β4-C-terminus peptide in the pipette solution, it was possible to evoke resurgent currents in small DRGs and in Nav1.7 or Nav1.6 expressing HEK293/N1E115 cells, which were enhanced by the presence of extracellular ATX-II. When injected into the skin of healthy volunteers, ATX-II induces painful and itch-like sensations which were abolished by mechanical nerve block. Increase in superficial blood flow of the skin, measured by Laser doppler imaging is limited to the injection site, so no axon reflex erythema as a correlate for C-fiber activation was detected.

Conclusion:

ATX-II enhances persistent and resurgent sodium currents in large diameter DRGs, whereas small DRGs depend on the addition of β4-peptide to the pipette recording solution for ATX-II to affect resurgent currents. Mechanical A-fiber blockade abolishes all ATX-II effects in human skin (e.g. painful and itch-like paraesthesias), suggesting that it mediates its effects mainly via activation of A-fibers.
PCR based bronchoscopic detection of common respiratory pathogens in chronic cough: a case control study
Authors: West Peter W , Kelsall Angela , Decalmer Samantha , Dove Winifred , Bishop Paul W , Stewart James P , Woodcock Ashley A , Smith Jaclyn A
Published: September 2012

Background

Viral respiratory tract infection is the most frequent cause of acute cough and is reported at onset in about one third of patients with chronic cough. Persistent infection is therefore one possible explanation for the cough reflex hypersensitivity and pulmonary inflammation reported in chronic cough patients.

Methods

Bronchoscopic endobronchial biopsies and bronchoalveolar lavage cell counts were obtained from ten healthy volunteers and twenty treatment resistant chronic cough patients (10 selected for lavage lymphocytosis). A screen for known respiratory pathogens was performed on biopsy tissue. Chronic cough patients also underwent cough reflex sensitivity testing using citric acid.

Results

There was no significant difference in incidence of infection between healthy volunteers and chronic cough patients (p = 0.115) or non-lymphocytic and lymphocytic groups (p = 0.404). BAL cell percentages were not significantly different between healthy volunteers and chronic cough patients without lymphocytosis. Lymphocytic patients however had a significantly raised percentage of lymphocytes (p < 0.01), neutrophils (p < 0.05), eosinophils (p < 0.05) and decreased macrophages (p < 0.001) verses healthy volunteers. There was no significant difference in the cough reflex sensitivity between non-lymphocytic and lymphocytic patients (p = 0.536).

Conclusions

This study indicates latent infection in the lung is unlikely to play an important role in chronic cough, but a role for undetected or undetectable pathogens in either the lung or a distal site could not be ruled out.

Trials registration

Current Controlled Trials ISRCTN62337037 & ISRCTN40147207
Male median raphe cysts: serial retrospective analysis and histopathological classification
Authors: Shao I-Hung , Chen Tai-Di , Shao Hsiang-Te , Chen Hsiao-Wen
Published: September 2012

Background

To review the clinical and pathological characteristics of median raphe cysts and to classify the lesions according to pathogenesis and histopathological findings.

Methods

The medical records of patients who were diagnosed with median raphe cysts between 2001 and 2010 were reviewed to document the clinical presentation and pathological findings of the cysts.

Results

Most patients were asymptomatic; however, 9 patients had inflammatory or infectious cysts that were tender or painful. Four patients who had cysts on the parameatus and distal prepuce had difficulty voiding. Hematuria and hematospermia were noted in 2 cases. Thirty-one cysts were lined with an urothelium-like epithelium, and a squamous epithelium lining was found in 3 cases. In 2 cases, a well-formed mucinous glandular structure was observed. The other 20 cysts consisted of mixed epithelia. After excision of the cysts under local or general anesthesia, an urethral fistula developed as a complication in only 1 case.

Conclusions

Median raphe cysts are benign lesions formed due to tissue trapping during the development of urethral folds. The cysts can be defined into 4 types based on pathological findings: urethral, epidermoid, glandular, and mixed. The associated symptoms and signs should be taken into consideration when determining the treatment for the cysts.

Virtual slides

The virtual slide(s) for this article can be found here: http//http://www.diagnosticpathology.diagnomx.eu/vs/7727074877500751
Inflammatory angiomyolipoma of the liver: a rare hepatic tumor
Authors: Liu Yang , Wang Jian , Lin Xu-Yong , Xu Hong-Tao , Qiu Xue-shan , Wang En-Hua
Published: September 2012

Angiomyolipoma (AML) is a rare mesenchymal neoplasm of the tumor, composed of a varying heterogeneous mixture of three tissue components: blood vessels, smooth muscle and adipose cells. Hepatic AML may demonstrate a marked histological diversity. We herein present one case of hepatic AML exhibiting prominent inflammatory cells in the background, which happened in a 61-year-old Chinese female patient, without signs of tuberous sclerosis. Histologically, the striking feature was the infiltration of numerous inflammatory cells in the background, including small lymphocytes, plasma cells, and eosnophils. The tumor cells were spindled and histiocytoid in shape, with slightly eosinophilic cytoplasm, and arranged along the vessels or scattered among the inflammatory background. Sinusoid structure was obviously seen in the tumor. Mature adipocytes and thick-walled blood vessels were focally observed at the boundaries between the tumor and surrounding liver tissues. The tumor cells were positive immunostaining for HMB-45, Melan-A, and smooth muscle actin. The inflammatory AML should be distinguished from other tumors with inflammatory background such as inflammatory myofibroblastic tumor and follicular dendritic cell tumor and deserves wider recognition for its occurrence as a primary hepatic tumor.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1828633072762370
The impact of preoperative anxiety and education level on long-term mortality after cardiac surgery
Authors: Cserép Zsuzsanna , Losoncz Eszter , Balog Piroska , Szili-Török Tamás , Husz András , Juhász Boglárka , Kertai Miklós D , Gál János , Székely Andrea
Published: September 2012

Background

Psychosocial factors have shown independent predictive value in the development of cardiovascular diseases. Although there is strong evidence to support the role of psychosocial factors in cardiovascular mortality, there is a scarcity of knowledge about how these factors are related. Therefore, we investigated the relationship between depression, anxiety, education, social isolation and mortality 7.5 years after cardiac surgery.

Methods

After informed consent, 180 patients undergoing cardiac surgery between July 2000 and May 2001 were prospectively enrolled and followed for ten years. During the follow-up period, the patients were contacted annually by mail. Anxiety (Spielberger State-Trait Anxiety Inventory, STAI-S/STAI-T), depression (Beck Depression Inventory, BDI) and the number and reason for rehospitalizations were assessed each year. Those patients who did not respond were contacted by telephone, and national registries were searched for deaths.

Results

During a median follow-up of 7.6 years (25th to 75th percentile, 7.4 to 8.1 years), the mortality rate was 23.6% (95% confidence interval [CI] 17.3-29.9; 42 deaths). In a Cox regression model, the risk factors associated with an increased risk of mortality were a higher EUROSCORE (points; Adjusted Hazard Ratio (AHR):1.30, 95%CI:1.07-1.58)), a higher preoperative STAI-T score (points; AHR:1.06, 95%CI 1.02-1.09), lower education level (school years; AHR:0.86, 95%CI:0.74-0.98), and the occurrence of major adverse cardiac and cerebral events during follow up (AHR:7.24, 95%CI:2.65-19.7). In the postdischarge model, the same risk factors remained.

Conclusions

Our results suggest that the assessment of psychosocial factors, particularly anxiety and education may help identify patients at an increased risk for long-term mortality after cardiac surgery.
A genome-scale metabolic model of the lipid-accumulating yeast Yarrowia lipolytica
Authors: Loira Nicolas , Dulermo Thierry , Nicaud Jean-Marc , Sherman David James
Published: September 2012

Background

Yarrowia lipolytica is an oleaginous yeast which has emerged as an important microorganism for several biotechnological processes, such as the production of organic acids, lipases and proteases. It is also considered a good candidate for single-cell oil production. Although some of its metabolic pathways are well studied, its metabolic engineering is hindered by the lack of a genome-scale model that integrates the current knowledge about its metabolism.

Results

Combining in silico tools and expert manual curation, we have produced an accurate genome-scale metabolic model for Y. lipolytica. Using a scaffold derived from a functional metabolic model of the well-studied but phylogenetically distant yeast S. cerevisiae, we mapped conserved reactions, rewrote gene associations, added species-specific reactions and inserted specialized copies of scaffold reactions to account for species-specific expansion of protein families. We used physiological measures obtained under lab conditions to validate our predictions.

Conclusions

Y. lipolytica iNL895 represents the first well-annotated metabolic model of an oleaginous yeast, providing a base for future metabolic improvement, and a starting point for the metabolic reconstruction of other species in the Yarrowia clade and other oleaginous yeasts.
Affinity for, and localization of, PEG-functionalized silica nanoparticles to sites of damage in an ex vivo spinal cord injury model
Authors: Chen Bojun , Zuberi Mahvash , Borgens Richard Ben , Cho Youngnam
Published: September 2012

Background

Traumatic spinal cord injury ( SCI) leads to serious neurological and functional deficits through a chain of pathophysiological events. At the molecular level, progressive damage is initially revealed by collapse of plasma membrane organization and integrity produced by breaches. Consequently, the loss of its role as a semi-permeable barrier that generally mediates the regulation and transport of ions and molecules eventually results in cell death. In previous studies, we have demonstrated the functional recovery of compromised plasma membranes can be induced by the application of the hydrophilic polymer polyethylene glycol (PEG) after both spinal and brain trauma in adult rats and guinea pigs. Additionally, efforts have been directed towards a nanoparticle-based PEG application.

The in vivo and ex vivo applications of PEG-decorated silica nanoparticles following CNS injury were able to effectively and efficiently enhance resealing of damaged cell membranes.

Results

The possibility for selectivity of tetramethyl rhodamine-dextran (TMR) dye-doped, PEG-functionalized silica nanoparticles (TMR-PSiNPs) to damaged spinal cord was evaluated using an ex vivo model of guinea pig SCI. Crushed and nearby undamaged spinal cord tissues exhibited an obvious difference in both the imbibement and accumulation of the TMR-PSiNPs, revealing selective labeling of compression-injured tissues.

Conclusions

These data show that appropriately functionalized nanoparticles can be an efficient means to both 1.) carry drugs, and 2.) apply membrane repair agents where they are needed in focally damaged nervous tissue.
Mitochondrial fission and fusion in Dictyostelium discoideum: a search for proteins involved in membrane dynamics
Authors: Schimmel Brixey G , Berbusse Gregory W , Naylor Kari
Published: September 2012

Background

Mitochondrial morphology is maintained by two distinct membrane events -fission and fusion. Altering these conserved processes can disrupt mitochondrial morphology and distribution, thereby disrupting the organelle’s functionality and impeding cellular function. In higher eukaryotes, these processes are mediated by a family of dynamin-related proteins (DRP’s). In the lower eukaryotes, for instance Dictyostelium discoideum, mitochondrial fission and fusion have been implicated but not yet established. To understand the overall mechanism of these dynamics across organisms, we developed an assay to identify fission and fusion events in Dictyostelium and to assess the involvement of the mitochondrial proteins, MidA, CluA, and two DRP’s, DymA and DymB.

Findings

Using laser scanning confocal microscopy we show, for the first time, that lower eukaryotes mediate mitochondrial fission and fusion. In Dictyostelium, these processes are balanced, occurring approximately 1 event/minute. Quantification of the rates in midA
-, cluA
-, dymA

-
, or dymB

-
strains established that MidA appears to play an indirect role in the regulation of fission and fusion, while the DRP’s are not essential for these processes. Rates of fission and fusion were significantly reduced in cluA
-cells, indicating that CluA is necessary for maintaining both fission and fusion.

Conclusions

We have successfully demonstrated that Dictyostelium mitochondria undergo the dynamic processes of fission and fusion. The classical mediators of membrane dynamics - the DRP’s – are not necessary for these dynamics, whereas CluA is necessary for both processes. This work contributes to our overall understanding of mitochondrial dynamics and ultimately will provide additional insight into mitochondrial disease.
Identification of suitable endogenous control genes for microRNA expression profiling of childhood medulloblastoma and human neural stem cells
Authors: Genovesi Laura A , Anderson Denise , Carter Kim W , Giles Keith M , Dallas Peter B
Published: September 2012

Background

Medulloblastoma (MB) is the most common type of malignant childhood brain tumour. Although deregulated microRNA (miRNA) expression has been linked to MB pathogenesis, the selection of appropriate candidate endogenous control (EC) reference genes for MB miRNA expression profiling studies has not been systematically addressed. In this study we utilised reverse transcriptase quantitative PCR (RT-qPCR) to identify the most appropriate EC reference genes for the accurate normalisation of miRNA expression data in primary human MB specimens and neural stem cells.

Results

Expression profiling of 662 miRNAs and six small nuclear/ nucleolar RNAs in primary human MB specimens, two CD133+ neural stem cell (NSC) populations and two CD133- neural progenitor cell (NPC) populations was performed using TaqMan low-density array (TLDA) cards. Minimal intra-card variability for candidate EC reference gene replicates was observed, however significant inter-card variability was identified between replicates present on both TLDA cards A and B. A panel of 18 potentially suitable EC reference genes was identified for the normalisation of miRNA expression on TLDA cards. These candidates were not significantly differentially expressed between CD133+ NSCs/ CD133- NPCs and primary MB specimens. Of the six sn/snoRNA EC reference genes recommended by the manufacturer, only RNU44 was uniformly expressed between primary MB specimens and CD133+ NSC/CD133- NPC populations (P = 0.709; FC = 1.02). The suitability of candidate EC reference genes was assessed using geNorm and NormFinder software, with hsa-miR-301a and hsa-miR-339-5p found to be the most uniformly expressed EC reference genes on TLDA card A and hsa-miR-425* and RNU24 for TLDA card B.

Conclusions

A panel of 18 potential EC reference genes that were not significantly differentially expressed between CD133+ NSCs/ CD133- NPCs and primary human MB specimens was identified. The top ranked EC reference genes described here should be validated in a larger cohort of specimens to verify their utility as controls for the normalisation of RT-qPCR data generated in MB miRNA expression studies. Importantly, inter-card variability observed between replicates of certain candidate EC reference genes has major implications for the accurate normalisation of miRNA expression data obtained using the miRNA TLDA platform.