bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic analysis of ‘Suli’ pear (Pyrus pyrifolia white pear group) buds during the dormancy by RNA-Seq
Authors: Liu Guoqin , Li Wanshun , Zheng Penghua , Xu Tong , Chen Lijuan , Liu Dongfeng , Hussain Sayed , Teng Yuanwen
Published: December 2012

Background

Bud dormancy is a critical developmental process that allows perennial plants to survive unfavorable environmental conditions. Pear is one of the most important deciduous fruit trees in the world, but the mechanisms regulating bud dormancy in this species are unknown. Because genomic information for pear is currently unavailable, transcriptome and digital gene expression data for this species would be valuable resources to better understand the molecular and biological mechanisms regulating its bud dormancy.

Results

We performedde novotranscriptome assembly and digital gene expression (DGE) profiling analyses of ‘Suli’ pear (Pyrus pyrifoliawhite pear group) using the Illumina RNA-seq system. RNA-Seq generated approximately 100 M high-quality reads that were assembled into 69,393 unigenes (mean length = 853 bp), including 14,531 clusters and 34,194 singletons. A total of 51,448 (74.1%) unigenes were annotated using public protein databases with a cut-off E-value above 10-5. We mainly compared gene expression levels at four time-points during bud dormancy. Between Nov. 15 and Dec. 15, Dec. 15 and Jan. 15, and Jan. 15 and Feb. 15, 1,978, 1,024, and 3,468 genes were differentially expressed, respectively. Hierarchical clustering analysis arranged 190 significantly differentially-expressed genes into seven groups. Seven genes were randomly selected to confirm their expression levels using quantitative real-time PCR.

Conclusions

The new transcriptomes offer comprehensive sequence and DGE profiling data for a dynamic view of transcriptomic variation during bud dormancy in pear. These data provided a basis for future studies of metabolism during bud dormancy in non-model but economically-important perennial species.
Bacillus cereus Fnr binds a [4Fe-4S] cluster and forms a ternary complex with ResD and PlcR
Authors: Esbelin Julia , Jouanneau Yves , Duport Catherine
Published: December 2012

Background

Bacillus cereus is a facultative anaerobe that causes diarrheal disease in humans. Diarrheal syndrome may result from the secretion of various virulence factors including hemolysin BL and nonhemolytic enterotoxin Nhe. Expression of genes encoding Hbl and Nhe is regulated by the two redox systems, ResDE and Fnr, and the virulence regulator PlcR. B. cereus Fnr is a member of the Crp/Fnr family of iron-sulfur (Fe-S) proteins. Only its apo-form has so far been studied. A major goal in deciphering the Fnr-dependent regulation of enterotoxin genes is thus to obtain and characterize holoFnr.

Results

Fnr has been subjected to in vitro Fe-S cluster reconstitution under anoxic conditions. UV-visible and EPR spectroscopic analyses together with the chemical estimation of the iron content indicated that Fnr binds one [4Fe-4S]2+ cluster per monomer. Atmospheric O2 causes disassembly of the Fe-S cluster, which exhibited a half-life of 15 min in air. Holo- and apoFnr have similar affinities for the nhe and hbl promoter regions, while holoFnr has a higher affinity for fnr promoter region than apoFnr. Both the apo- and holo-form of Fnr interact with ResD and PlcR to form a ternary complex.

Conclusions

Overall, this work shows that incorporation of the [4Fe-4S]2+ cluster is not required for DNA binding of Fnr to promoter regions of hbl and nhe enterotoxin genes or for the formation of a ternary complex with ResD and PlcR. This points to some new unusual properties of Fnr that may have physiological relevance in the redox regulation of enterotoxin gene regulation.
Canadian adolescent mothers’ perceptions of influences on breastfeeding decisions: a qualitative descriptive study
Authors: Nesbitt Sherry A , Campbell Karen A , Jack Susan M , Robinson Heather , Piehl Kathleen , Bogdan Janice C
Published: December 2012

Background

There is increased recognition of the importance of breastfeeding at a national level as evidenced by the increased number of Canadian mothers initiating breastfeeding. However, adolescent mothers (<19 years), compared to all other mothers, have lower rates of breastfeeding initiation and duration. The purpose of this study was to examine the facilitating influences and barriers to initiating, and continuing breastfeeding, as perceived by adolescent mothers in Durham Region, Ontario, Canada.

Methods

The principles of interpretive description guided this qualitative study. A purposeful, homogenous sample of 16 adolescent mothers (15–19 years) were recruited to complete individual, semi-structured, face-to-face interviews. Conventional content analysis was used to code data, identify concepts and synthesize them into overall themes.

Results

Adolescent mothers in this study expressed that the decision to breastfeed was made prenatally and while partner and family member opinions about breastfeeding initiation were influential, the decision was made independently. Mothers were primarily motivated to initiate breastfeeding due to the health benefits for the infant. Lower breastfeeding duration rates were found among mothers who decided to only “try” breastfeeding when compared to the mothers who committed to breastfeeding. Influences on continued breastfeeding included: 1) the impact of breastfeeding on social and intimate relationships; 2) the availability of social support; 3) the physical demands of breastfeeding; 4) mothers’ knowledge of breastfeeding practices and benefits; and 5) mothers’ perceived sense of comfort in breastfeeding.

Conclusions

The results of this study provide health care providers new conceptual insight and understanding of the factors that influence adolescents’ decisions to “try” breastfeeding and to continue providing breastmilk to their infants. Professional implications drawn from this study include active engagement of adolescents in the pre and postnatal periods, including early assessment of potential barriers surrounding breastfeeding decisions. This early professional interaction highlights the professional as a form of support, and allows for sharing of evidence-informed breastfeeding information and practical breastfeeding skills. Inclusion of adolescents’ positive social support networks should be emphasized in professional breastfeeding support. Motivational interviewing is a promising prenatal strategy to influence behavior change and reduce ambivalence in decision-making about breastfeeding, creating opportunities for health care providers to tailor interventions.
Association of p21 SNPs and risk of cervical cancer among Chinese women
Authors: Wang Ning , Wang Shizhuo , Zhang Qiao , Lu Yanming , Wei Heng , Li Wei , Zhang Shulan , Yin Duo , Ou Yangling
Published: December 2012

Background

The p21 codon 31 single nucleotide polymorphism (SNP), rs1801270, has been linked to cervical cancer but with controversial results. The aims of this study were to investigate the role of p21 SNP-rs1801270 and other untested p21 SNPs in the risk of cervical cancer in a Chinese population.

Methods

We genotyped five p21 SNPs (rs762623, rs2395655, rs1801270, rs3176352, and rs1059234) using peripheral blood DNA from 393 cervical cancer patients and 434 controls.

Results

The frequency of the rs1801270 A allele in patients (0.421) was significantly lower than that in controls (0.494, p = 0.003). The frequency of the rs3176352 C allele in cases (0.319) was significantly lower than that in controls (0.417, p < 0.001).The allele frequency of other three p21 SNPs showed not statistically significantly different between patients and controls. The rs1801270 AA genotype was associated with a decreased risk for the development of cervical cancer (OR = 0.583, 95%CI: 0.399 - 0.853, P = 0.005). We observed that the three p21 SNPs (rs1801270, rs3176352, and rs1059234) was in linkage disequilibrium (LD) and thus haplotype analysis was performed. The AGT haplotype (which includes the rs1801270A allele) was the most frequent haplotype among all subjects, and both homozygosity and heterozygosity for the AGT haplotype provided a protective effect from development of cervical cancer.

Conclusions

We show an association between the p21 SNP rs1801270A allele and a decreased risk for cervical cancer in a population of Chinese women. The AGT haplotype formed by three p21 SNPs in LD (rs1801270, rs3176352 and rs1059234) also provided a protective effect in development of cervical cancer in this population.
“Iron-saturated” bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice
Authors: Sun Xueying , Jiang Ruohan , Przepiorski Aneta , Reddy Shiva , Palmano Kate P , Krissansen Geoffrey W
Published: December 2012

Background

Tamoxifen is used in hormone therapy for estrogen-receptor (ER)-positive breast cancer, but also has chemopreventative effects against ER-negative breast cancers. This study sought to investigate whether oral iron-saturated bovine lactoferrin (Fe-Lf), a natural product which enhances chemotherapy, could improve the chemotherapeutic effects of tamoxifen in the treatment of ER-negative breast cancers.

Methods

In a model of breast cancer prevention, female Balb/c mice treated with tamoxifen (5 mg/Kg) were fed an Fe-Lf supplemented diet (5 g/Kg diet) or the base diet. At week 2, 4T1 mammary carcinoma cells were injected into an inguinal mammary fat pad. In a model of breast cancer treatment, tamoxifen treatment was not started until two weeks following tumor cell injection. Tumor growth, metastasis, body weight, and levels of interleukin 18 (IL-18) and interferon γ (IFN-γ) were analyzed.

Results

Tamoxifen weakly (IC50 ~ 8 μM) inhibited the proliferation of 4T1 cells at pharmacological concentrations in vitro. In the tumor prevention study, a Fe-Lf diet in combination with tamoxifen caused a 4 day delay in tumor formation, and significantly inhibited tumor growth and metastasis to the liver and lung by 48, 58, and 66% (all P < 0.001), respectively, compared to untreated controls. The combination therapy was significantly (all P < 0.05) more effective than the respective monotherapies. Oral Fe-Lf attenuated the loss of body weight caused by tamoxifen and cancer cachexia. It prevented tamoxifen-induced reductions in serum levels of IL-18 and IFN-γ, and intestinal cells expressing IL-18 and IFN-γ. It increased the levels of Lf in leukocytes residing in gut-associated lymphoid tissues. B, T and Natural killer (NK) cells containing high levels of Lf were identified in 4T1 tumors, suggesting they had migrated from the intestine. Similar effects of Fe-Lf and tamoxifen on tumor cell viability were seen in the treatment of established tumors.

Conclusions

The results indicate that Fe-Lf is a potent natural adjuvant capable of augmenting the chemotherapeutic activity of tamoxifen. It could have application in delaying relapse in tamoxifen-treated breast cancer patients who are at risk of developing ER-negative tumors.
Causes and risk factors for infant mortality in Nunavut, Canada 1999–2011
Authors: Collins Sorcha A , Surmala Padma , Osborne Geraldine , Greenberg Cheryl , Bathory Laakkuluk Williamson , Edmunds-Potvin Sharon , Arbour Laura
Published: December 2012

Background

The northern territory Nunavut has Canada’s largest jurisdictional land mass with 33,322 inhabitants, of which 85% self-identify as Inuit. Nunavut has rates of infant mortality, postneonatal mortality and hospitalisation of infants for respiratory infections that greatly exceed those for the rest of Canada. The infant mortality rate in Nunavut is 3 times the national average, and twice that of the neighbouring territory, the Northwest Territories. Nunavut has the largest Inuit population in Canada, a population which has been identified as having high rates of Sudden Infant Death Syndrome (SIDS) and infant deaths due to infections.

Methods

To determine the causes and potential risk factors of infant mortality in Nunavut, we reviewed all infant deaths (<1yr) documented by the Nunavut Chief Coroner’s Office and the Nunavut Bureau of Statistics (n=117; 1999–2011). Rates were compared to published data for Canada.

Results

Sudden death in infancy (SIDS/SUDI; 48%) and infection (21%) were the leading causes of infant death, with rates significantly higher than for Canada (2003–2007). Of SIDS/SUDI cases with information on sleep position (n=42) and bed-sharing (n=47), 29 (69%) were sleeping non-supine and 33 (70%) were bed-sharing. Of those bed-sharing, 23 (70%) had two or more additional risk factors present, usually non-supine sleep position. CPT1A P479L homozygosity, which has been previously associated with infant mortality in Alaska Native and British Columbia First Nations populations, was associated with unexpected infant death (SIDS/SUDI, infection) throughout Nunavut (OR:3.43, 95% CI:1.30-11.47).

Conclusion

Unexpected infant deaths comprise the majority of infant deaths in Nunavut. Although the CPT1A P479L variant was associated with unexpected infant death in Nunavut as a whole, the association was less apparent when population stratification was considered. Strategies to promote safe sleep practices and further understand other potential risk factors for infant mortality (P479L variant, respiratory illness) are underway with local partners.
Decline in male circumcision in South Korea
Authors: Kim DaiSik , Koo Sung-Ae , Pang Myung-Geol
Published: December 2012

Background

To investigate the changing circumcision rate in South Korea in the last decade and to propose underlying causes for this change, in the context of the present fluctuating world-wide trends in circumcision.

Methods

From 2009 to 2011, 3,296 South Korean males (or their parents) aged 0–64 years were asked about their circumcision status, their age at circumcision, and their information level regarding circumcision. We employed non-probability sampling considering the sensitive questions on the study theme.

Results

Currently the age-standardized circumcision rate for South Korean males aged 14–29 is found to be 75.8%. In an earlier study performed in 2002, the rate for the same age group was 86.3%. Of particular interest, males aged 14–16 show a circumcision rate of 56.4%, while the same age group 10 years ago displayed a much higher percentage, at 88.4%. In addition, the extraordinarily high circumcision rate of 95.2% found 10 years ago for the 17–19 age group is now reduced to 74.4%. Interestingly, of the circumcised males, the percentage circumcised in the last decade was only 25.2%; i.e., the majority of the currently circumcised males had undergone the operation prior to 2002, indicating that the actual change in the last decade is far greater. Consistent with this conjecture, the 2002 survey showed that the majority of circumcised males (75.7%) had undergone the operation in the decade prior to that point. Focusing on the flagship age group of 14–16, this drop suggests that, considering the population structure of Korean males, approximately one million fewer circumcision operations have been performed in the last decade relative to the case of non-decline. This decline is strongly correlated with the information available through internet, newspapers, lectures, books, and television: within the circumcised population, both the patients and their parents had less prior knowledge regarding circumcision, other than information obtained from person to person by oral communication. Within the uncircumcised population, the prior knowledge was far greater, suggesting that information discouraging circumcision played an important role.

Conclusion

South Korean male circumcision is likely to be undergoing a steep decline. The cause for this decline seems to be the increase in information available on the pros and cons of circumcision.
Evaluation of the OnSite (Pf/Pan) rapid diagnostic test for diagnosis of clinical malaria
Authors: Mohon Abu Naser , Elahi Rubayet , Podder Milka Patracia , Mohiuddin Khaja , Hossain Mohammad Sharif , Khan Wasif A , Haque Rashidul , Alam Mohammad Shafiul
Published: December 2012

Background

Accurate diagnosis of malaria is an essential prerequisite for proper treatment and drug resistance monitoring. Microscopy is considered the gold standard for malaria diagnosis but has limitations. ELISA, PCR, and Real Time PCR are also used to diagnose malaria in reference laboratories, although their application at the field level is currently not feasible. Rapid diagnostic tests (RDTs) however, have been brought into field operation and widely adopted in recent days. This study evaluatesOnSite(Pf/Pan) antigen test, a new RDT introduced by CTK Biotech Inc, USA for malaria diagnosis in a reference setting.

Methods

Blood samples were collected from febrile patients referred for malaria diagnosis by clinicians. Subjects were included in this study from two different Upazila Health Complexes (UHCs) situated in two malaria endemic districts of Bangladesh. Microscopy and nested PCR were considered the gold standard in this study.OnSite(Pf/Pan) RDT was performed on preserved whole blood samples.

Results

In total, 372 febrile subjects were included in this study. Of these subjects, 229 (61.6%) tested positive forPlasmodiuminfection detected by microscopy and nested PCR.OnSite(Pf/Pan) RDT was 94.2% sensitive (95% CI, 89.3-97.3) and 99.5% specific (95% CI, 97.4-00.0) forPlasmodium falciparumdiagnosis and 97.3% sensitive (95% CI, 90.5-99.7) and 98.7% specific (95% CI, 96.6-99.6) forPlasmodium vivaxdiagnosis. Sensitivity varied with differential parasite count for bothP. falciparumandP. vivax. The highest sensitivity was observed in febrile patients with parasitaemia that ranged from 501–1,000 parasites/μL regardless of thePlasmodiumspecies.

Conclusion

The newOnSite(Pf/Pan) RDT is both sensitive and specific for symptomatic malaria diagnosis in standard laboratory conditions.
Situs inversus totalis with carcinoma of gastric cardia: a case report
Authors: Ke Pan , Dewu Zhong , Xiongying Miao , Guoqing Liu , Qunguang Jiang , Yi Liu
Published: December 2012

Situs inversus is an uncommon anomaly with rare incidence. Some cases of situs inversus totalis have been described with different types of associations. Here we report a case of situs inversus with carcinoma of the gastric cardia.
Prognostic value of expression of molecular markers in adenoid cystic cancer of the salivary glands compared with lymph node metastasis: a retrospective study
Authors: Lee Seok Ki , Kwon Min Su , Lee Yoon Se , Choi Seung-Ho , Kim Sang Yoon , Cho Kyoung Ja , Nam Soon Yuhl
Published: December 2012

Background

Adenoid cystic cancer arising in the salivary glands has distinctive features such as perineural invasion, distant metastasis, and a variable prognosis. In salivary gland cancer, c-kit, EGFR, and VEGF are representative molecular markers that may predict remnant and recurrent tumors. In this study, the expression of c-kit, EGFR, and VEGF in adenoid cystic cancer was evaluated, and the relationships between the expression of these markers and the clinical findings were investigated.

Methods

The medical records of 48 patients who were treated for parotid adenoid cystic cancer from January 1990 to January 2006 were reviewed. The tumor location, size, histological subtypes, perineural invasion, the resected margin status, and lymph node metastasis were assessed. Immunohistochemical staining and semiquantitative analysis of c-kit, EGFR and VEGF were performed. The relationship between the expression of each marker and the clinicopathological factors were analyzed.

Results

Positive c-kit immunostaining was present in 45 patients (94%), with weak positivity (+1) in 23, moderate positivity (+2) in 19 and strong positivity (+3) in three. Positive EGFR immunostaining was observed in 27 (56%), with weak positivity (+1) in 19 and moderate positivity (+2) in eight with no strong positive staining. Positive VEGF immunostaining was present in 42 patients (88%) with weak positivity (+1) in 12, moderate positivity (+2) in 17, and strong positivity (+3) in 13. Only the expression of VEGF was significantly higher in parotid gland tumors than in any other gland (P = 0.032). Marginal involvement was associated with strong VEGF expression (P = 0.02). No marker was significantly correlated with recurrence or the survival rate. Lymph node status was related to the survival rate.

Conclusions

The expression of c-kit, EGRF, and VEGF had no predictive value for recurrence or the prognosis of adenoid cystic cancer. Only the lymph node status was related to the prognosis.
u-PA inhibitor amiloride suppresses peritoneal metastasis in gastric cancer
Authors: Ding Youcheng , Zhang Hui , Zhou Zhuqing , Zhong Mingan , Chen Qiliang , Wang Xujing , Zhu Zhenggang
Published: December 2012

Background

Peritoneal metastasis in gastric cancer represents a ubiquitous human health problem but effective therapies with limited side effects are still lacking. Although previous research suggested that u-PA was involved in some tumor metastasis such as lung-specific metastasis, the role of u-PA for peritoneal metastasis in gastric cancer is still unclear. The aim of this study was to explore whether selective pharmacological blockade of u-PA is able to affect the peritoneal metastasis of gastric cancer both in vivo and in vitro.

Methods

In the present study, we evaluated the effects and explored the anti-tumor mechanisms of amiloride, a selective u-PA inhibitor, on a panel of gastric cancer cell lines and in a murine model of human gastric cancer MKN45.

Results

The study showed that amiloride significantly inhibited the tumor growth and prolonged the survival of the tumor-bearing mice. In vitro, compared with controls, amiloride could not only significantly down-regulate the mRNA expression and protein level of u-PA from MKN45 cells with dose dependence but also inhibit the adhesion of HMrSV5 cells, migration and invasion of MKN45 cells.

Conclusions

The findings in our current report provide evidence that selective u-PA inhibitor amiloride has potent effects against peritoneal metastasis in gastric cancer, suggesting its possible therapeutic value for the treatment of gastric cancer.
Indoleamine 2,3-dioxygenase 1 (IDO1) activity correlates with immune system abnormalities in multiple myeloma
Authors: Bonanno Giuseppina , Mariotti Andrea , Procoli Annabella , Folgiero Valentina , Natale Daniela , De Rosa Luca , Majolino Ignazio , Novarese Linda , Rocci Alberto , Gambella Manuela , Ciciarello Marilena , Scambia Giovanni , Palumbo Antonio , Locatelli Franco , De Cristofaro Raimondo , Rutella Sergio
Published: December 2012

Background

Multiple myeloma (MM) is a plasma cell malignancy with a multifaceted immune dysfunction. Indoleamine 2,3-dioxygenase 1 (IDO1) degrades tryptophan into kynurenine (KYN), which inhibits effector T cells and promote regulatory T-cell (Treg) differentiation. It is presently unknown whether MM cells express IDO1 and whether IDO1 activity correlates with immune system impairment.

Methods

We investigated IDO1 expression in 25 consecutive patients with symptomatic MM and in 7 patients with either monoclonal gammopathy of unknown significance (MGUS; n=3) or smoldering MM (SMM; n=4). IDO1-driven tryptophan breakdown was correlated with the release of hepatocyte growth factor (HGF) and with the frequency of Treg cells and NY-ESO-1-specific CD8+ T cells.

Results

KYN was increased in 75% of patients with symptomatic MM and correlated with the expansion of CD4+CD25+FoxP3+ Treg cells and the contraction of NY-ESO-1-specific CD8+ T cells. In vitro, primary MM cells promoted the differentiation of allogeneic CD4+ T cells into bona fide CD4+CD25hiFoxP3hi Treg cells and suppressed IFN-γ/IL-2 secretion, while preserving IL-4 and IL-10 production. Both Treg expansion and inhibition of Th1 differentiation by MM cells were reverted, at least in part, by d,l-1-methyl-tryptophan, a chemical inhibitor of IDO. Notably, HGF levels were higher within the BM microenvironment of patients with IDO+ myeloma disease compared with patients having IDO- MM. Mechanistically, the antagonism of MET receptor for HGF with SU11274, a MET inhibitor, prevented HGF-induced AKT phosphorylation in MM cells and translated into reduced IDO protein levels and functional activity.

Conclusions

These data suggest that IDO1 expression may contribute to immune suppression in patients with MM and possibly other HGF-producing cancers.
An effective oxidation approach for luminescence enhancement in CdS quantum dots by H2O2
Authors: Lee Woojin , Kim Hoechang , Jung Dae-Ryong , Kim Jongmin , Nahm Changwoo , Lee Junhee , Kang Suji , Lee Byungho , Park Byungwoo
Published: December 2012

The effects of surface passivation on the photoluminescence (PL) properties of CdS nanoparticles oxidized by straightforward H2O2 injection were examined. Compared to pristine cadmium sulfide nanocrystals (quantum efficiency ≅ 0.1%), the surface-passivated CdS nanoparticles showed significantly enhanced luminescence properties (quantum efficiency ≅ 20%). The surface passivation by H2O2 injection was characterized using X-ray photoelectron spectroscopy, X-ray diffraction, and time-resolved PL. The photoluminescence enhancement is due to the two-order increase in the radiative recombination rate by the sulfate passivation layer.
Convergence theorems for mixed type asymptotically nonexpansive mappings
Authors: Guo Weiping , Cho Yeol Je , Guo Wei
Published: December 2012

In this paper, we introduce a new two-step iterative scheme of mixed type for two asymptotically nonexpansive self-mappings and two asymptotically nonexpansive nonself-mappings and prove strong and weak convergence theorems for the new two-step iterative scheme in uniformly convex Banach spaces.
SAMHD1 restricts HIV-1 infection in dendritic cells (DCs) by dNTP depletion, but its expression in DCs and primary CD4+T-lymphocytes cannot be upregulated by interferons
Authors: St Gelais Corine , de Silva Suresh , Amie Sarah M , Coleman Christopher M , Hoy Heather , Hollenbaugh Joseph A , Kim Baek , Wu Li
Published: December 2012

Background

SAMHD1 is an HIV-1 restriction factor in non-dividing monocytes, dendritic cells (DCs), macrophages, and resting CD4+ T-cells. Acting as a deoxynucleoside triphosphate (dNTP) triphosphohydrolase, SAMHD1 hydrolyzes dNTPs and restricts HIV-1 infection in macrophages and resting CD4+ T-cells by decreasing the intracellular dNTP pool. However, the intracellular dNTP pool in DCs and its regulation by SAMHD1 remain unclear. SAMHD1 has been reported as a type I interferon (IFN)-inducible protein, but whether type I IFNs upregulate SAMHD1 expression in primary DCs and CD4+ T-lymphocytes is unknown.

Results

Here, we report that SAMHD1 significantly blocked single-cycle and replication-competent HIV-1 infection of DCs by decreasing the intracellular dNTP pool and thereby limiting the accumulation of HIV-1 late reverse transcription products. Type I IFN treatment did not upregulate endogenous SAMHD1 expression in primary DCs or CD4+ T-lymphocytes, but did in HEK 293T and HeLa cell lines. When SAMHD1 was over-expressed in these two cell lines to achieve higher levels than that in DCs, no HIV-1 restriction was observed despite partially reducing the intracellular dNTP pool.

Conclusions

Our results suggest that SAMHD1-mediated reduction of the intracellular dNTP pool in DCs is a common mechanism of HIV-1 restriction in myeloid cells. Endogenous expression of SAMHD1 in primary DCs or CD4+ T-lymphocytes is not upregulated by type I IFNs.
Fulminant hepatic failure in association with quetiapine: a case report
Authors: Al Mutairi Fawaz , Dwivedi Girish , Al Ameel Turki
Published: December 2012

Introduction

Fulminant hepatic failure is a serious disease with significant mortality and morbidity. Identifying the exact cause of hepatic failure and predicting prognosis is of paramount importance in managing such patients. Drug-induced liver injury is a common but challenging entity to treat. The use of newer drugs and medications with previously unknown hepatotoxicity add to the challenges faced by treating physicians. Quetiapine is an antipsychotic that has rarely been linked to acute liver injury. In the present work we describe a case of fulminant hepatic failure secondary to use of quetiapine.

Case presentation

A 59-year-old Caucasian woman with known Parkinson’s disease was being treated with quetiapine for hallucinations. She was referred to our hospital with yellow discoloration of the sclera and later on developed clinical features suggestive of hepatic encephalopathy. A diagnosis of fulminant hepatic failure was made following her admission to the intensive care unit. Her condition improved after discontinuing the drug and providing the standard supportive treatment.

Conclusions

Our findings in the present report emphasize the importance of keeping an open mind in cases of fulminant hepatic failure. As drug-induced hepatotoxicity is the most common cause of fulminant hepatic failure in many parts of the world, consideration should be given to the medication(s) patients receive as the potential cause and a review of this list should be part of the clinical care given.
New species of Ehrlichia isolated from Rhipicephalus (Boophilus) microplus shows an ortholog of the E. canis major immunogenic glycoprotein gp36 with a new sequence of tandem repeats
Authors: Cruz Alejandro Cabezas , Zweygarth Erich , Ribeiro Mucio Flavio Barbosa , da Silveira Julia Angelica Gonçalves , de la Fuente Jose , Grubhoffer Libor , Valdés James J , Passos Lygia Maria Friche
Published: December 2012

Background

Ehrlichia species are the etiological agents of emerging and life-threatening tick-borne human zoonoses that inflict serious and fatal infections in companion animals and livestock. The aim of this paper was to phylogeneticaly characterise a new species of Ehrlichia isolated from Rhipicephalus (Boophilus) microplus from Minas Gerais, Brazil.

Methods

The agent was isolated from the hemolymph of Rhipicephalus (B.) microplus engorged females that had been collected from naturally infested cattle in a farm in the state of Minas Gerais, Brazil. This agent was then established and cultured in IDE8 tick cells. The molecular and phylogenetic analysis was based on 16S rRNA, groEL, dsb, gltA and gp36 genes. We used the maximum likelihood method to construct the phylogenetic trees.

Results

The phylogenetic trees based on 16S rRNA, groEL, dsb and gltA showed that the Ehrlichia spp isolated in this study falls in a clade separated from any previously reported Ehrlichia spp. The molecular analysis of the ortholog of gp36, the major immunoreactive glycoproteins in E. canis and ortholog of the E. chaffeensis gp47, showed a unique tandem repeat of 9 amino acids (VPAASGDAQ) when compared with those reported for E. canis, E. chaffeensis and the related mucin-like protein in E. ruminantium.

Conclusions

Based on the molecular and phylogenetic analysis of the 16S rRNA, groEL, dsb and gltA genes we concluded that this tick-derived microorganism isolated in Brazil is a new species, named E. mineirensis (UFMG-EV), with predicted novel antigenic properties in the gp36 ortholog glycoprotein. Further studies on this new Ehrlichia spp should address questions about its transmissibility by ticks and its pathogenicity for mammalian hosts.
Familial gastric cancer: detection of a hereditary cause helps to understand its etiology
Authors: Vogelaar Ingrid P , van der Post Rachel S , Bisseling Tanya M , van Krieken J Han JM , Ligtenberg Marjolijn JL , Hoogerbrugge Nicoline
Published: December 2012

Worldwide, gastric cancer is one of the most common forms of cancer, with a high morbidity and mortality. Several environmental factors predispose to the development of gastric cancer, such as Helicobacter pylori infection, diet and smoking. Familial clustering of gastric cancer is seen in 10% of cases, and approximately 3% of gastric cancer cases arise in the setting of hereditary diffuse gastric cancer (HDGC). In families with HDGC, gastric cancer presents at relatively young age. Germline mutations in the CDH1 gene are the major cause of HDGC and are identified in approximately 25-50% of families which fulfill strict criteria. Prophylactic gastrectomy is the only option to prevent gastric cancer in individuals with a CDH1 mutation. However, in the majority of families with multiple cases of gastric cancer no germline genetic abnormality can be identified and therefore preventive measures are not available, except for general lifestyle advice. Future research should focus on identifying new genetic predisposing factors for all types of familial gastric cancer.
Synthesis and biological evaluation of propargyl acetate derivatives as anti-mycobacterial agents
Authors: Azerang Parisa , Rezayan Ali Hossein , Sardari Soroush , Kobarfard Farzad , Bayat Mitra , Tabib Kimia
Published: December 2012

Background

The emergence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb) has intensified efforts to discover novel drugs for tuberculosis (TB) treatment. Targeting the persistent state of Mtb, a condition in which Mtb is resistant to conventional drug therapies, is of particular interest.

Methods

This study is focused on propargyl acetate derivatives. Eight molecules were designed based on propargyl alcohols and different acid anhydrides.

Results

All the synthesized compounds and commercially available ones were evaluated for anti-tuberculosis activity.

Conclusions

Inhibitors against Mtb have been identified and characterized for further development into potential novel anti-tubercular drugs.
Multiple essential roles for primary cilia in heart development
Authors: Willaredt Marc August , Gorgas Karin , Gardner Humphrey A R , Tucker Kerry L
Published: December 2012

Background

The primary cilium is a microtubule-based, plasma membrane-ensheathed protrusion projecting from the basal bodies of almost all cell types in the mammalian body. In the past several years a plethora of papers has indicated a crucial role for primary cilia in the development of a wide variety of organs. We have investigated heart development in cobblestone, a hypomorphic allele of the gene encoding the intraflagellar transport protein Ift88, and uncovered a number of the most common congenital heart defects seen in newborn humans.

Methods

We generated serial sections of mutant cobblestone and wild type embryos in the region encompassing the heart and the cardiac outflow tract. The sections were further processed to generate three-dimensional reconstructions of these structures, and immunofluorescence confocal microscopy, transmission electron microscopy, and in situ hybridization were used to examine signal transduction pathways in the relevant areas. Whole mount in situ hybridization was also employed for certain developmental markers.

Results

In addition to an enlarged pericardium and failure of both ventricular and atrial septum formation, the cobblestone mutants displayed manifold defects in outflow tract formation, including persistent truncus arteriosus, an overriding aorta, and abnormal transformation of the aortic arches. To discern the basis of these anomalies we examined both the maintenance of primary cilia as well as endogenous and migratory embryonic cell populations that contribute to the outflow tract and atrioventricular septa. The colonization of the embryonic heart by cardiac neural crest occurred normally in the cobblestone mutant, as did the expression of Sonic hedgehog. However, with the loss of primary cilia in the mutant hearts, there was a loss of both downstream Sonic hedgehog signaling and of Islet 1 expression in the second heart field, a derivative of the pharyngeal mesoderm. In addition, defects were recorded in development of atrial laterality and ventricular myocardiogenesis. Finally, we observed a reduction in expression of Bmp4 in the outflow tract, and complete loss of expression of both Bmp2 and Bmp4 in the atrioventricular endocardial cushions. Loss of BMP2/4 signaling may result in the observed proliferative defect in the endocardial cushions, which give rise to both the atrioventricular septa as well as to the septation of the outflow tract.

Conclusions

Taken together, our results potentially identify a novel link between Sonic hedgehog signaling at the primary cilium and BMP-dependent effects upon cardiogenesis. Our data further point to a potential linkage of atrioventricular septal defects, the most common congenital heart defects, to genes of the transport machinery or basal body of the cilia.
Assessing telomeric DNA content in pediatric cancers using whole-genome sequencing data
Authors: Parker Matthew , Chen Xiang , Bahrami Armita , Dalton James , Rusch Michael , Wu Gang , Easton John , Cheung Nai-Kong , Dyer Michael , Mardis Elaine R , Wilson Richard K , Mullighan Charles , Gilbertson Richard , Baker Suzanne J , Zambetti Gerard , Ellison David W , Downing James R , Zhang Jinghui ,   Pediatric Cancer Genome Project
Published: December 2012

Background

Telomeres are the protective arrays of tandem TTAGGG sequence and associated proteins at the termini of chromosomes. Telomeres shorten at each cell division due to the end-replication problem and are maintained above a critical threshold in malignant cancer cells to prevent cellular senescence or apoptosis. With the recent advances in massive parallel sequencing, assessing telomere content in the context of other cancer genomic aberrations becomes an attractive possibility. We present the first comprehensive analysis of telomeric DNA content change in tumors using whole-genome sequencing data from 235 pediatric cancers.

Results

To measure telomeric DNA content, we counted telomeric reads containing TTAGGGx4 or CCCTAAx4 and normalized to the average genomic coverage. Changes in telomeric DNA content in tumor genomes were clustered using a Bayesian Information Criterion to determine loss, no change, or gain. Using this approach, we found that the pattern of telomeric DNA alteration varies dramatically across the landscape of pediatric malignancies: telomere gain was found in 32% of solid tumors, 4% of brain tumors and 0% of hematopoietic malignancies. The results were validated by three independent experimental approaches and reveal significant association of telomere gain with the frequency of somatic sequence mutations and structural variations.

Conclusions

Telomere DNA content measurement using whole-genome sequencing data is a reliable approach that can generate useful insights into the landscape of the cancer genome. Measuring the change in telomeric DNA during malignant progression is likely to be a useful metric when considering telomeres in the context of the whole genome.
Tracking of velocity variations at depth in the presence of surface velocity fluctuations
Authors: de Cacqueray Benoit , Roux Philippe , Campillo Michel , Catheline Stefan
Published: December 2012

We tested a small-scale experiment that is dedicated to the study of the wave separation algorithm and to the velocity variations monitoring problem itself. It handles the case in which velocity variations at depth are hidden by near-surface velocity fluctuations. Using an acquisition system that combines an array of sources and an array of receivers, coupled with controlled velocity variations, we tested the ability of beam-forming techniques to track velocity variations separately for body waves and surface waves. After wave separation through double beam forming, the arrival time variations of the different waves were measured through the phase difference between the extracted wavelets. Finally, a method was tested to estimate near-surface velocity variations using surface waves or shallow reflection and compute a correction to isolate target velocity variations at depth.
Impact of Age on Outcomes After Initial Therapy With Chemotherapy and Different Chemoimmunotherapy Regimens in Patients With Chronic Lymphocytic Leukemia: Results of Sequential Cancer and Leukemia Group B Studies
Authors: Woyach Jennifer A. , Ruppert Amy S. , Rai Kanti , Lin Thomas S. , Geyer Susan , Kolitz Jonathan , Appelbaum Frederick R. , Tallman Martin S. , Belch Andrew R. , Morrison Vicki A. , Larson Richard A. , Byrd John C.
Published: December 2012

Purpose

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, yet few clinical trials include a significant number of older patients, and outcomes after specific therapies can be different depending on age.

Patients and Methods

We examined patients enrolled onto successive first-line CALGB CLL trials to determine whether efficacy of regimens varied by age, focusing on ideal chemotherapy choice and benefit of immunotherapy addition to chemotherapy in older patients. Regimens included chlorambucil, fludarabine, fludarabine plus rituximab (FR), fludarabine with consolidation alemtuzumab, and FR with consolidation alemtuzumab.

Results

A total of 663 patients were evaluated for response, progression-free survival (PFS), and overall survival (OS) by age group. Interaction effects of fludarabine versus chlorambucil by age group (PFS, P = .046; OS, P = .006) showed that among patients younger than 70 years, PFS and OS was improved with fludarabine over chlorambucil (PFS: hazard ratio [HR] = 0.6, 95% CI, 0.5 to 0.8; OS: HR = 0.7, 95% CI, 0.5 to 0.9), but not in older adults (PFS, HR = 1.0, 95% CI, 0.6 to 1.7; OS: HR = 1.5, 95% CI, 0.9 to 2.3). In contrast, FR improved outcomes relative to fludarabine, irrespective of age (PFS: HR = 0.6, 95% CI, 0.4 to 0.7; OS: HR = 0.7, 95% CI, 0.5 to 0.9). Alemtuzumab consolidation did not provide benefit over similar regimens without alemtuzumab (P > .20), irrespective of age.

Conclusion

These data support the use of chlorambucil as an acceptable treatment for many older patients with CLL and suggest rituximab is beneficial regardless of age. These findings bear relevance to both routine care of CLL patients 70 years and older and also future clinical trials in this population.
Randomized Controlled Trial of a Video Decision Support Tool for Cardiopulmonary Resuscitation Decision Making in Advanced Cancer
Authors: Volandes Angelo E. , Paasche-Orlow Michael K. , Mitchell Susan L. , El-Jawahri Areej , Davis Aretha Delight , Barry Michael J. , Hartshorn Kevan L. , Jackson Vicki Ann , Gillick Muriel R. , Walker-Corkery Elizabeth S. , Chang Yuchiao , López Lenny , Kemeny Margaret , Bulone Linda , Mann Eileen , Misra Sumi , Peachey Matt , Abbo Elmer D. , Eichler April F. , Epstein Andrew S. , Noy Ariela , Levin Tomer T. , Temel Jennifer S.
Published: December 2012

Purpose

Decision making regarding cardiopulmonary resuscitation (CPR) is challenging. This study examined the effect of a video decision support tool on CPR preferences among patients with advanced cancer.

Patients and Methods

We performed a randomized controlled trial of 150 patients with advanced cancer from four oncology centers. Participants in the control arm (n = 80) listened to a verbal narrative describing CPR and the likelihood of successful resuscitation. Participants in the intervention arm (n = 70) listened to the identical narrative and viewed a 3-minute video depicting a patient on a ventilator and CPR being performed on a simulated patient. The primary outcome was participants' preference for or against CPR measured immediately after exposure to either modality. Secondary outcomes were participants' knowledge of CPR (score range of 0 to 4, with higher score indicating more knowledge) and comfort with video.

Results

The mean age of participants was 62 years (standard deviation, 11 years); 49% were women, 44% were African American or Latino, and 47% had lung or colon cancer. After the verbal narrative, in the control arm, 38 participants (48%) wanted CPR, 41 (51%) wanted no CPR, and one (1%) was uncertain. In contrast, in the intervention arm, 14 participants (20%) wanted CPR, 55 (79%) wanted no CPR, and 1 (1%) was uncertain (unadjusted odds ratio, 3.5; 95% CI, 1.7 to 7.2; P < .001). Mean knowledge scores were higher in the intervention arm than in the control arm (3.3 ± 1.0 v 2.6 ± 1.3, respectively; P < .001), and 65 participants (93%) in the intervention arm were comfortable watching the video.

Conclusion

Participants with advanced cancer who viewed a video of CPR were less likely to opt for CPR than those who listened to a verbal narrative.
Enlightened Reforms and Economic Discourse in the Portuguese-Brazilian Empire (1750–1808)
Authors: Cardoso José Luís , Cunha Alexandre Mendes
Published: December 2012

In this article we discuss the role of political economy in the design and implementation of economic and political reforms that occurred in Brazil in the second half of the eighteenth century. Brazil was during this period still a part, the most important part, of the Portuguese empire. The reading of economic texts of this period allows for an interpretation of the role played by the enlightened economic literature to challenge and transform the existing structures of the old colonial regime, as well as to prepare Brazil for its future path of economic and political independence. The new visions and representations of the empire were put forward by authors faithful to enlightened mercantilist and cameralist doctrines supporting the reform of colonial administration. However, the most relevant policy measures were implemented under the shadow of Adam Smith, whose system of political economy also included a new way of looking at both the nature of colonial trade and the need for its reform.
On-Line near Infrared Monitoring of Ammonium and Dry Matter in Bioslurry for Robust Biogas Production: A Full-Scale Feasibility Study
Authors: Madsen Michael , Ihunegbo Felicia N. , Holm-Nielsen Jens Bo , Halstensen Maths , Esbensen Kim H.
Published: December 2012

Heterogeneous substrates fed into agricultural biogas plants originate from many sources with resulting quality fluctuations potentially inhibiting the process. Biogas yield can be substantially increased by optimisation of the organic dry matter load. In this study, near infrared (NIR) spectroscopy was applied on-line in a re-circulating loop configuration operating identically as a full-scale setup. Ammonium could be modelled in the industrially-relevant range 2.42–8.52 gL−1 with an excellent accuracy and precision, slope ∼1.0, r2 = 0.97, corresponding to a relative root mean square error of prediction ( RMSEP) of 6.7%. Also, dry matter in the similar plant relevant range 5.8–10.8 weight-percent could be predicted with acceptable accuracy (slope ∼1.0, r2 = 0.83, and a relative RMSEP below 8.0%. Based on these performance characteristics, it was concluded that NIR spectroscopy can be applied for optimising the efficiency of current and future biogas plants, as well as in biorefinery operations converting heterogeneous bioslurry, energy crops, and wastes into value-added products.
Clustering, Agency Costs and Operating Efficiency: Evidence from Nursing Home Chains
Authors: Lu Susan F. , Wedig Gerard J.
Published: December 2012

Models of horizontal integration typically describe a trade-off between multiunit efficiencies and managerial agency costs. In extreme cases where managers cannot be incented contractually, private ownership is thought to be the primary organizational substitute. In this paper we explore geographic clustering as an alternative strategy for controlling managerial agency costs within the chain form of organization. Clustering may facilitate scale efficiencies in both monitoring and supervision, resulting in reduced agency costs and improved application of the chain's business model. We test this hypothesis in the nursing home industry, which is characterized by managerial contract costs resulting from multitask models of production. We find that clustered nursing homes achieve higher quality, conditional on labor inputs and patient characteristics. The clustering effect is concentrated on reductions in minor/potential harm violations, which are difficult to observe without close monitoring. Several proxies for local organizational experience (“local learning”) cannot account for our findings, which are robust to a variety of alternative clustering definitions and competing explanations based on gaming behavior. Further tests indicate that chains endogenously pursue clustering, presumably to realize the benefits of improved quality outcomes.

This paper was accepted by Bruno Cassiman, business strategy.