bluuebunny/crossref_metadata_2025 huggingface dataset:
Satisfaction–Adaptation Principles in Sexual Desire
Authors: Gebauer Jochen E. , Baumeister Roy F. , Sedikides Constantine , Neberich Wiebke
Published: June 2013

Sexual desire may change according to two principles: the satisfaction principle (high sexual opportunity/frequency decreases sexual desire) and the adaptation principle (high sexual opportunity/frequency increases sexual desire). We explore the workings of these opposing principles separately for both genders across the adult life span. Two tests within a large ( N = 181,546) and cross-cultural (11 countries) data set revealed that the satisfaction principle accounts for sexual desire in men throughout the entire life and it accounts for sexual desire in women until their mid-30s. From that point onward, however, the pattern of female sexual desire becomes increasingly consistent with the adaptation principle. What sets older women apart from younger women and men of all ages? We discuss several mechanisms, with a focus on the satisfaction principle’s evolutionary value in life phases of high reproductive capacity and the adaptation principle’s evolutionary value in life phases of low reproductive capacity.
Airborne Outreach
Authors: Reid Michael J. A. , Haverkamp Miriam , McAllister Tammi , Miller Jonathan , Kirk Brianna L.
Published: June 2013

There is a paucity of research demonstrating how HIV-funded services in Africa have improved equity and access to non-HIV services for both HIV-infected and uninfected patients. In this short communication, we describe the impact of an airborne outreach program to provide HIV services to high-HIV burden health facilities in rural Botswana. The analysis demonstrates how this HIV-funded program enhanced access to essential subspecialist services at several rural health facilities across Botswana.
Evolution by selection, recombination, and gene duplication in MHC class I genes of two Rhacophoridae species
Authors: Zhao Mian , Wang Yongzhen , Shen Hang , Li Chenliang , Chen Cheng , Luo Zhenhua , Wu Hua
Published: June 2013

Background

Comparison of major histocompatibility complex (MHC) genes across vertebrate species can reveal molecular mechanisms underlying the evolution of adaptive immunity-related proteins. As the first terrestrial tetrapods, amphibians deserve special attention because of their exposure to probably increased spectrum of microorganisms compared with ancestral aquatic fishes. Knowledge regarding the evolutionary patterns and mechanisms associated with amphibian MHC genes remains limited. The goal of the present study was to isolate MHC class I genes from two Rhacophoridae species (Rhacophorus omeimontisandPolypedates megacephalus) and examine their evolution.

Results

We identified 27 MHC class I alleles spanning the region from exon 2 to 4 in 38 tree frogs. The available evidence suggests that these 27 sequences all belong to classical MHC class I (MHC Ia) genes. Although several anuran species only display one MHC class Ia locus, at least two or three loci were observed inP. megacephalusandR. omeimontis,indicating that the number of MHC class Ia loci varies among anuran species. Recombination events, which mainly involve the entire exons, played an important role in shaping the genetic diversity of the 27 MHC class Ia alleles. In addition, signals of positive selection were found in Rhacophoridae MHC class Ia genes. Amino acid sites strongly suggested by program to be under positive selection basically accorded with the putative antigen binding sites deduced from crystal structure of human HLA. Phylogenetic relationships among MHC class I alleles revealed the presence of trans-species polymorphisms.

Conclusions

In the two Rhacophoridae species (1) there are two or three MHC class Ia loci; (2) recombination mainly occurs between the entire exons of MHC class Ia genes; (3) balancing selection, gene duplication and recombination all contribute to the diversity of MHC class Ia genes. These findings broaden our knowledge on the evolution of amphibian MHC systems.
Distinct transcriptome profiles identified in normal human bronchial epithelial cells after exposure to γ-rays and different elemental particles of high Z and energy
Authors: Ding Liang-Hao , Park Seongmi , Peyton Michael , Girard Luc , Xie Yang , Minna John D , Story Michael D
Published: June 2013

Background

Ionizing radiation composed of accelerated ions of high atomic number (Z) and energy (HZE) deposits energy and creates damage in cells in a discrete manner as compared to the random deposition of energy and damage seen with low energy radiations such as γ- or x-rays. Such radiations can be highly effective at cell killing, transformation, and oncogenesis, all of which are concerns for the manned space program and for the burgeoning field of HZE particle radiotherapy for cancer. Furthermore, there are differences in the extent to which cells or tissues respond to such exposures that may be unrelated to absorbed dose. Therefore, we asked whether the energy deposition patterns produced by different radiation types would cause different molecular responses. We performed transcriptome profiling using human bronchial epithelial cells (HBECs) after exposure to γ-rays and to two different HZE particles (28Si and 56Fe) with different energy transfer properties to characterize the molecular response to HZE particles and γ-rays as a function of dose, energy deposition pattern, and time post-irradiation.

Results

Clonogenic assay indicated that the relative biological effectiveness (RBE) for 56Fe was 3.91 and for 28Si was 1.38 at 34% cell survival. Unsupervised clustering analysis of gene expression segregated samples according to the radiation species followed by the time after irradiation, whereas dose was not a significant parameter for segregation of radiation response. While a subset of genes associated with p53-signaling, such as CDKN1A, TRIM22 and BTG2 showed very similar responses to all radiation qualities, distinct expression changes were associated with the different radiation species. Gene enrichment analysis categorized the differentially expressed genes into functional groups related to cell death and cell cycle regulation for all radiation types, while gene pathway analysis revealed that the pro-inflammatory Acute Phase Response Signaling was specifically induced after HZE particle irradiation. A 73 gene signature capable of predicting with 96% accuracy the radiation species to which cells were exposed, was developed.

Conclusions

These data suggest that the molecular response to the radiation species used here is a function of the energy deposition characteristics of the radiation species. This novel molecular response to HZE particles may have implications for radiotherapy including particle selection for therapy and risk for second cancers, risk for cancers from diagnostic radiation exposures, as well as NASA’s efforts to develop more accurate lung cancer risk estimates for astronaut safety. Lastly, irrespective of the source of radiation, the gene expression changes observed set the stage for functional studies of initiation or progression of radiation-induced lung carcinogenesis.
The genome and transcriptome of the pine saprophyte Ophiostoma piceae, and a comparison with the bark beetle-associated pine pathogen Grosmannia clavigera
Authors: Haridas Sajeet , Wang Ye , Lim Lynette , Massoumi Alamouti Sepideh , Jackman Shaun , Docking Rod , Robertson Gordon , Birol Inanc , Bohlmann Jörg , Breuil Colette
Published: June 2013

Background

Ophiostoma piceae is a wood-staining fungus that grows in the sapwood of conifer logs and lumber. We sequenced its genome and analyzed its transcriptomes under a range of growth conditions. A comparison with the genome and transcriptomes of the mountain pine beetle-associated pathogen Grosmannia clavigera highlights differences between a pathogen that colonizes and kills living pine trees and a saprophyte that colonizes wood and the inner bark of dead trees.

Results

We assembled a 33 Mbp genome in 45 scaffolds, and predicted approximately 8,884 genes. The genome size and gene content were similar to those of other ascomycetes. Despite having similar ecological niches, O. piceae and G. clavigera showed no large-scale synteny. We identified O. piceae genes involved in the biosynthesis of melanin, which causes wood discoloration and reduces the commercial value of wood products. We also identified genes and pathways involved in growth on simple carbon sources and in sapwood, O. piceae’s natural substrate. Like the pathogen, the saprophyte is able to tolerate terpenes, which are a major class of pine tree defense compounds; unlike the pathogen, it cannot utilize monoterpenes as a carbon source.

Conclusions

This work makes available the second annotated genome of a softwood ophiostomatoid fungus, and suggests that O. piceae’s tolerance to terpenes may be due in part to these chemicals being removed from the cells by an ABC transporter that is highly induced by terpenes. The data generated will provide the research community with resources for work on host-vector-fungus interactions for wood-inhabiting, beetle-associated saprophytes and pathogens.
Telmisartan protects against microvascular dysfunction during myocardial ischemia/reperfusion injury by activation of peroxisome proliferator-activated receptor gamma
Authors: Zeng Xiao-Cong , Li Xing-San , Wen Hong
Published: June 2013

Background

We investigated the potential of telmisartan to improve microvascular dysfunction induced by myocardial ischemia/reperfusion (I/R) injury by activating the peroxisome proliferator-activated receptor gamma (PPARG) pathway.

Methods

Forty-eight male rabbits were randomly allocated into sham-operated, I/R, GW9662, telmisartan, telmisartan–GW9662, or candesartan groups. Rabbits were anesthetized, and the left anterior descending coronary artery (LAD) was ligated for 60 minutes. Following reperfusion for 6 hours, angiotensin II content of the heart was determined using radioimmunoassay. Myocardial neutrophil accumulation and microvessel cross-sectional area were examined histologically. Myocardial capillaries were examined with transmission electron microscopy. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the myocardium were measured using enzyme-linked immunosorbent assay. Western blot was utilized for investigating the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-
κ
B) and PPARG.

Results

Angiotensin II concentration was significantly increased in all treatment groups compared with the sham-operated group (P < 0.05, all). Accumulation of polymorphonuclear neutrophils was significantly lower, while microvessel cross-sectional area was significantly higher in the telmisartan, telmisartan-GW9662, and candesartan groups compared with the I/R group (P < 0.05). ICAM-1 and VCAM-1 levels were also significantly lower, and correlated with lower NF-
κ
B expression in these groups. The effects were the most significant in the telmisartan group compared with the telmisartan–GW9662 and candesartan groups. Telmisartan significantly increased PPARG protein expression compared with all other groups (P < 0.05, all).

Conclusions

Except for the typical effects of angiotensin II-receptor blocker, telmisartan improved microvascular dysfunction during myocardial I/R injury via the PPARG pathway.
Incidence, risk factors, and outcomes of Fusobacterium species bacteremia
Authors: Afra Kevin , Laupland Kevin , Leal Jenine , Lloyd Tracie , Gregson Daniel
Published: June 2013

Background

Fusobacterium species (spp.) bacteremia is uncommon and has been associated with a variety of clinical presentations. We conducted a retrospective, population based study to determine the relative proportion of species in this genus causing bacteremia and the risk factors for infection and adverse clinical outcomes.

Methods

All cases of Fusobacterium spp. bacteremia detected at a regional microbiology laboratory serving outpatient and acute care for a population of approximately 1.3 million people over 11 years were identified from a computerized database. Clinical data on these cases was extracted from an administrative database and analyzed to determine underlying risk factors for and outcomes of infection.

Results

There were 72 incident cases of Fusobacterium spp. bacteremia over the study period (0.55 cases/100,000 population per annum). F. nucleatum was the most frequent species (61%), followed by F. necrophorum (25%). F. necrophorum bacteremia occurred in a younger population without underlying comorbidities and was not associated with mortality. F. nucleatum bacteremia was found in an older population and was associated with underlying malignancy or receiving dialysis. Death occurred in approximately 10% of F. nucleatum cases but causality was not established in this study.

Conclusions

Fusobacterium spp. bacteremia in our community is uncommon and occurs in approximately 5.5 cases per million population per annum. F. necrophorum occurred in an otherwise young healthy population and was not associated with any mortality. F. nucleatum was found primarily in older patients with chronic medical conditions and was associated with a mortality of approximately 10%. Bacteremias from other Fusobacterium spp. were rare.
Metabolic syndrome, C-reactive protein and microalbuminuria in a rural Chinese population: a cross-sectional study
Authors: Jiang Liping , Huang Wen , Liang Yuanbo , Wang Fenghua , Duan Xinrong , Yang Xiaohui , Wen Jiangping , Wang Ningli
Published: June 2013

Background

Microalbuminuria is an early marker of chronic kidney disease (CKD). Previous studies have shown that either metabolic syndrome (MetS) or chronic inflammation is related to renal impairment. The aim of this study was to investigate the association between MetS, C-reactive protein (CRP) and microalbuminuria in a rural Chinese population.

Methods

This was a cross-sectional study using data from the Handan Eye Study. MetS was defined according to the Chinese Diabetes Society (CDS) criteria. CRP levels ≥ 3 mg/L were classified as high CRP. Microalbuminuria was defined as a urinary albumin/creatinine ratio (ACR) of 30–300 mg/g.

Results

We included 4191 subjects aged ≥ 30 years in this analysis. The prevalence of MetS and microalbuminuria in the group was 25.7% and 15.6%, respectively. The odds ratio (OR) of microalbuminuria in subjects with MetS was 1.25 (95% confidence interval (CI): 1.03 − 1.51) compared with those without microalbuminuria. In multivariate logistic regression analysis, high blood pressure (OR 1.36, 95% CI: 1.10 − 1.67) and high fasting blood glucose (OR 1.44, 95% CI: 1.17 − 1.76) were independently associated with microalbuminuria. Subjects with high CRP and MetS had a 1.46-fold greater risk of having microalbuminuria compared with those with low CRP without MetS (95% CI: 1.06 − 2.01).

Conclusions

In this rural Chinese population aged ≥30 years, MetS and microalbuminuria were independently related and the combination of high CRP and MetS was associated with an increased risk of microalbuminuria.
Prediction of maternal quality of life on preterm birth and low birthweight: a longitudinal study
Authors: Wang Panchalli , Liou Shwu-Ru , Cheng Ching-Yu
Published: June 2013

Background

Preterm birth is a significant cause of newborn morbidity and mortality and strains society’s healthcare resources due to its long-term effects on the health of the newborn. Prenatal maternal quality of life (QoL) may be related to the occurrence of preterm birth and low birthweight infants. Few studies, however, have investigated maternal QoL, especially throughout the continuum of pregnancy and the immediate postpartum period. Therefore, the purposes of this longitudinal study were to measure the levels of QoL during and immediately after pregnancy in women with uncomplicated pregnancies, investigate the relationships between the dimensions of QoL, and determine whether prenatal QoL can predict preterm birth and low birthweight.

Methods

Using convenience sampling in one hospital in Taiwan, we recruited 198 pregnant women without pregnancy complications after 24 gestational weeks and followed up monthly until one-month postpartum. The Duke Health Profile was used to measure QoL. Data were analyzed using descriptive statistics, the Mann–WhitneyUtest, the Kruskal-Wallis test, generalized estimation equations, Pearson correlations, and hierarchical logistic regression.

Results

Pregnant women did not perceive that they had a high level of QoL. Women at late pregnancy experienced a significant decrease in their level of physical and general health. After childbirth, although the mothers had better physical health, they had poorer social health. Poor QoL at late pregnancy predicted preterm birth. Employment, parity, educational level, and happiness about pregnancy were related to prenatal maternal QoL; employment was a factor related to postpartum maternal QoL.

Conclusions

Early assessment of QoL, including its dimensions, of pregnant women may help us to understand women’s health status. Based on this understanding, healthcare professionals can develop interventions to promote pregnant women’s QoL and to lessen the occurrence of preterm birth and low birthweight infants. Further, an emphasis on the positive aspects of pregnancy may increase maternal QoL.
Diagnostic accuracy of diffuse reflectance imaging for early detection of pre-malignant and malignant changes in the oral cavity: a feasibility study
Authors: Stephen Manju M , Jayanthi Jayaraj L , Unni Nisha G , Kolady Philip E , Beena Valappil T , Jeemon Panniyammakal , Subhash Narayanan
Published: June 2013

Background

Diffusely reflected light is influenced by cytologic and morphologic changes that take place during tissue transformation, such as, nuclear changes, extracellular matrix structure and composition as well as blood flow. Albeit with varying degree of sensitivity and specificity, the properties of diffusely reflected light in discriminating a variety of oral lesions have been demonstrated by our group in multiple studies using point monitoring systems. However, the point monitoring system could not identify the region with the most malignant potential in a single sitting.

Methods

In order to scan the entire lesion, we developed a multi-spectral imaging camera system that records diffuse reflectance (DR) images of the oral lesion at 545 and 575 nm with white light illumination. The diagnostic accuracy of the system for 2-dimensional DR imaging of pre-malignant and malignant changes in the oral cavity was evaluated through a clinical study in 55 patients and 23 healthy volunteers. The DR imaging data were compared with gold standard tissue biopsy and histopathology results.

Results

In total 106- normal/clinically healthy sites, 20- pre-malignant and 29- malignant (SCC) sites were compared. While the median pixel value of the R545/R575 image ratio for normal/clinically healthy tissue was 0.87 (IQR = 0.82-0.94), they were 1.35 (IQR = 1.13-1.67) and 2.44 (IQR = 1.78-3.80) for pre-malignant and malignant lesions, respectively. Area under the ROC curve to differentiate malignant from normal/clinically healthy [AUC = 0.99 (95% CI: 0.99-1.00)], pre-malignant from normal/clinically healthy [AUC = 0.94 (95% CI: 0.86-1.00)], malignant from pre-malignant [AUC = 0.84 (95% CI: 0.73-0.95)] and pre-malignant and malignant from normal/clinically healthy [AUC = 0.97 (95% CI: 0.94-1.00)] lesions were desirable.

Conclusion

We find DR imaging to be very effective as a screening tool in locating the potentially malignant areas of oral lesions with relatively good diagnostic accuracy while comparing it to the gold standard histopathology.
EphA4 is a prognostic factor in gastric cancer
Authors: Miyazaki Kohji , Inokuchi Mikito , Takagi Yoko , Kato Keiji , Kojima Kazuyuki , Sugihara Kenichi
Published: June 2013

Background

Erythropoietin-producing hepatocellular (Eph) receptor, consisting of a family of receptor tyrosine kinases, plays critical roles in tumour development and is considered an attractive target for cancer therapy.

Methods

Tumour samples were obtained from 222 patients with gastric adenocarcinoma who underwent gastrectomy. The expressions of EphA2, EphA4, and ephrinA1 were evaluated immunohistochemically.

Results

High expressions of EphA2, EphA4, and ephrinA1 significantly correlated with variables related to tumour progression, including the depth of invasion, metastatic lymph nodes, pathological stage, and distant metastasis or recurrent disease. High expressions of EphA2, EphA4, and ephrinA1 were significantly associated with poorer disease-specific survival (DSS; p < 0.001, p < 0.001, p = 0.026). On multivariate analysis, EphA4 was an independent prognostic factor of DSS (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.1-4.8; p = 0.028), and EphA2 tended to be a prognostic factor (HR, 2.4; 95% CI, 1.0-5.8; p = 0.050). In stage II and III cancer, EphA4 and EphA2 were both significantly associated with shorter survival (p = 0.007 and 0.019), but only EphA2 was an independent prognostic factor (HR, 2.6; 95% CI, 1.1-6.3; p = 0.039).

Conclusion

EphA4 may play important roles in tumor progression and outcomes in patients with gastric cancer.
Eating habits of a population undergoing a rapid dietary transition: portion sizes of traditional and non-traditional foods and beverages consumed by Inuit adults in Nunavut, Canada
Authors: Sheehy Tony , Roache Cindy , Sharma Sangita
Published: June 2013

Background

To determine the portion sizes of traditional and non-traditional foods being consumed by Inuit adults in three remote communities in Nunavut, Canada.

Methods

A cross-sectional study was carried out between June and October, 2008. Trained field workers collected dietary data using a culturally appropriate, validated quantitative food frequency questionnaire (QFFQ) developed specifically for the study population.

Results

Caribou, muktuk (whale blubber and skin) and Arctic char (salmon family), were the most commonly consumed traditional foods; mean portion sizes for traditional foods ranged from 10 g for fermented seal fat to 424 g for fried caribou. Fried bannock and white bread were consumed by >85% of participants; mean portion sizes for these foods were 189 g and 70 g, respectively. Sugar-sweetened beverages and energy-dense, nutrient-poor foods were also widely consumed. Mean portion sizes for regular pop and sweetened juices with added sugar were 663 g and 572 g, respectively. Mean portion sizes for potato chips, pilot biscuits, cakes, chocolate and cookies were 59 g, 59 g, 106 g, 59 g, and 46 g, respectively.

Conclusions

The present study provides further evidence of the nutrition transition that is occurring among Inuit in the Canadian Arctic. It also highlights a number of foods and beverages that could be targeted in future nutritional intervention programs aimed at obesity and diet-related chronic disease prevention in these and other Inuit communities.
MutS homologue hMSH4: interaction with eIF3f and a role in NHEJ-mediated DSB repair
Authors: Chu Yen-Lin , Wu Xiling , Xu Yang , Her Chengtao
Published: June 2013

Background

DNA mismatch repair proteins participate in diverse cellular functions including DNA damage response and repair. As a member of this protein family, the molecular mechanisms of hMSH4 in mitotic cells are poorly defined. It is known that hMSH4 is promiscuous, and among various interactions the hMSH4-hMSH5 interaction is involved in recognizing DNA intermediate structures arising from homologous recombination (HR).

Results

We identified a new hMSH4 interacting protein eIF3f – a protein that functions not only in translation but also in the regulation of apoptosis and tumorigenesis in humans. Our studies have demonstrated that hMSH4-eIF3f interaction is mediated through the N-terminal regions of both proteins. The interaction with eIF3f fosters hMSH4 protein stabilization, which in turn sustains γ-H2AX foci and compromises cell survival in response to ionizing radiation (IR)-induced DNA damage. These effects can be, at least partially, attributed to the down-regulation of NHEJ activity by hMSH4. Furthermore, the interplay between hMSH4 and eIF3f inhibits IR-induced AKT activation, and hMSH4 promotes eIF3f-mediated bypass of S phase arrest, and ultimately enhancing an early G2/M arrest in response to IR treatment.

Conclusion

Our current study has revealed a role for hMSH4 in the maintenance of genomic stability by suppressing NHEJ-mediated DSB repair.
Fludarabine treatment favors the retention of miR-485-3p by prostate cancer cells: implications for survival
Authors: Lucotti Serena , Rainaldi Giuseppe , Evangelista Monica , Rizzo Milena
Published: June 2013

Background

Circulating microRNAs (miRNAs) have been found in many body fluids and represent reliable markers of several physio-pathological disorders, including cancer. In some cases, circulating miRNAs have been evaluated as markers of the efficacy of anticancer treatment but it is not yet clear if miRNAs are actively released by tumor cells or derive from dead tumor cells.

Results

We showed that a set of prostate cancer secretory miRNAs (PCS-miRNAs) were spontaneously released in the growth medium by DU-145 prostate cancer cells and that the release was greater after treatment with the cytotoxic drug fludarabine. We also found that the miRNAs were associated with exosomes, implying an active mechanism of miRNA release. It should be noted that in fludarabine treated cells the release of miR-485-3p, as well as its association with exosomes, was reduced suggesting that miR-485-3p was retained by surviving cells. Monitoring the intracellular level of miR-485-3p in these cells, we found that miR-485-3p was stably up regulated for several days after treatment. As a possible mechanism we suggest that fludarabine selected cells that harbor high levels of miR-485-3p, which in turn regulates the transcriptional repressor nuclear factor-Y triggering the transcription of topoisomerase IIα, multidrug resistance gene 1 and cyclin B2 pro-survival genes.

Conclusions

Cytotoxic treatment of DU-145 cells enhanced the release of PCS-miRNAs with the exception of miR-485-3p which was retained by surviving cells. We speculate that the retention of miR-485-3p was a side effect of fludarabine treatment in that the high intracellular level of miR-485-3p plays a role in the sensitivity to fludarabine.
Locally-advanced primary neuroendocrine carcinoma of the breast: case report and review of the literature
Authors: Angarita Fernando A , Rodríguez Jorge L , Meek Eugenio , Sánchez Jesus O , Tawil Mauricio , Torregrosa Lilian
Published: June 2013

Background

Primary neuroendocrine carcinoma of the breast is a heterogeneous group of rare tumors with positive immunoreactivity to neuroendocrine markers in at least 50% of cells. Diagnosis also requires that other primary sites be ruled out and that the same tumor show histological evidence of a breast in situ component. Primary neuroendocrine carcinoma of the breast rarely presents as locally advanced disease and less frequently with such widespread metastatic disease as described herein. The review accompanying this case report is the first to provide an overview of all the cases of primary neuroendocrine carcinoma of the breast published in the literature and encompasses detailed information regarding epidemiology, histogenesis, clinical and histologic diagnosis criteria, classification, surgical and adjuvant treatment, as well as prognosis. We also provide recommendations for common clinical and histologic pitfalls associated with this tumor.

Case presentation

We describe a case of a 51-year-old Hispanic woman initially diagnosed with locally-advanced invasive ductal carcinoma that did not respond to neodjuvant treatment. After undergoing modified radical mastectomy the final surgical pathology showed evidence of alveolar-type primary neuroendocrine carcinoma of the breast. The patient was treated with cisplatin/etoposide followed by paclitaxel/carboplatinum. Thirteen months after surgery the patient is alive, but developed pulmonary, bone, and hepatic metastasis.

Conclusion

The breast in situ component of primary neuroendocrine carcinoma of the breast may prevail on a core biopsy samples increasing the probability of underdiagnosing this tumor preoperatively. Being aware of the existence of this disease allows for timely diagnosis and management. Optimal treatment requires simultaneous consideration of both the neuroendocrine and breast in situ tumor features.
Tumor necrosis factor receptor superfamily 10B (TNFRSF10B): an insight from structure modeling to virtual screening for designing drug against head and neck cancer
Authors: Tahir Rana Adnan , Sehgal Sheikh Arslan , Khattak Naureen Aslam , Khan Khattak Jabar Zaman , Mir Asif
Published: June 2013

Background

Head and neck cancer (HNC) belongs to a group of heterogeneous disease with distinct patterns of behavior and presentation. TNFRSF10B, a tumor suppressor gene mapped on chromosome 8. Mutation in candidate gene is responsible for the loss of chromosome p arm which is frequently observed in head and neck tumors. TNFRSF10B inhibits tumor formation through apoptosis but deregulation encourages metastasis, migration and invasion of tumor cell tissues.

Results

Structural modeling was performed by employing MODELLER (9v10). A suitable template [2ZB9] was retrieved from protein databank with query coverage and sequence identity of 84% and 30% respectively. Predicted Model evaluation form Rampage revealed 93.2% residues in favoured region, 5.7% in allowed region while only 1 residue is in outlier region. ERRAT and ProSA demonstrated 51.85% overall quality with a −1.08 Z-score of predicted model. Molecular Evolutionary Genetics Analysis (MEGA 5) tool was executed to infer an evolutionary history of TNFRSF10B candidate gene. Orthologs and paralogs [TNFRSF10A & TNFRSF10D] protein sequences of TNFRSF10B gene were retrieved for developed ancestral relationship. Topology of tree presenting TNFRSF10A gene considered as outgroup. Human and gorilla shared more than 90% similarities with conserved amino acid sequence. Virtual screening approach was appliedfor identification of novel inhibitors. Library (Mcule) was screened for novel inhibitors and utilized the scrutinized lead compounds for protein ligand docking. Screened lead compounds were further investigated for molecular docking studies. STRING server was employed to explore protein-protein interactions of TNFRSF10B target protein. TNFSF10 protein showed highest 0.999 confidence score and selected protein-protein docking by utilizing GRAMM-X server.In-silicodocking results revealed I-58, S-90 and A-62 as most active interacting residues of TNFRSF10B receptor protein with R-130, S-156 and R-130 of TNFSF10B ligand protein.

Conclusion

Current research may provide a backbone for understanding structural and functional insights of TNFRSF10B protein. The designed novel inhibitors and predicted interactions might serve to inhibit the disease. Effectivein-vitropotent ligands are required which will be helpful in future to design a drug to against Head and neck cancer disease. There is an urgent need for affective drug designing of head and neck cancer and computational tools for examining candidate genes more efficiently and accurately are required.
NK cells improve control of friend virus infection in mice persistently infected with murine cytomegalovirus
Authors: Francois Sandra , Peng Jing , Schwarz Tatjana , Duppach Janine , Gibbert Kathrin , Dittmer Ulf , Kraft Anke RM
Published: June 2013

Background

Co-infection of HIV patients with cytomegalovirus (CMV) is associated with enhanced AIDS progression and CMV end-organ diseases. On the other hand, persistent CMV infection has recently been shown to decrease tumor relapse and protect against lethal bacterial infection. The influence of persistent CMV on the outcome of an acute retroviral superinfection is still unknown.

Results

Here we show that a persistent murine CMV (mCMV) infection surprisingly confers higher resistance to a primary Friend retrovirus infection (FV) of mice. Decreased FV titers and augmented FV-specific CD8 T-cell responses were found in mCMV infected mice during primary FV superinfection. NK cells produced higher amounts of IFNgamma after FV infection of persistently mCMV infected mice suggesting that these cells were involved in the ‘protective’ effect. Depletion of NK1.1+cells or neutralization of IFNgamma during FV superinfection abrogated the mCMV-mediated effect.

Conclusion

Our data demonstrate for the first time that a persistent CMV infection induces long-lasting NK cell responses that can enhance immunity to primary retroviral infections. To our knowledge, studies investigating primary HIV infection have not analyzed the role of the CMV seropositivity in these patients. Our observations suggest that NK cells in CMV seropositive individuals might contribute to the control of primary HIV infection.
Chikungunya virus with E1-A226V mutation causing two outbreaks in 2010, Guangdong, China
Authors: Wu De , Zhang Yonghui , ZhouHui Qiong , Kou Jing , Liang Wenjia , Zhang Huan , Monagin Corina , Zhang Qiaoli , Li Wenjie , Zhong Haojie , He Jianfeng , Li Hui , Cai Songwu , Ke Changwen , Lin Jinyan
Published: June 2013

Background

CHIKV is a mosquito-borne emerging pathogen that has a major health impact in humans in tropical zones around the globe. A new variant of the virus, E1-A226V caused a large outbreak in the Indian Ocean islands and India from 2004–2007. CHIKV outbreak was initially reported in Dongguan region of Guangdong in 2010 in China, another smaller CHIKV outbreak was found in Yangjiang region of Guangdong two weeks later. The viral agent causing the two outbreaks was inferred to be the new E1-A226V variant and Yangjiang CHIKV might be introduced from Dongguan. To confirm the hypothesis and determine the origin of CHIKV causing the outbreaks, we described Yangjiang outbreak in this study, and the molecular characterization of CHIKV from Yangjiang and Dongguang outbreaks were analyzed.

Results

27 clinical cases of CHIK fever were reported in outbreak in Yangjiang region. Sera sample from 12 clinical cases were collected from the outbreak, and nucleic acid and antibody tests for CHIKV were performed using Real-time RT-PCR and indirect immunofluorescence. Positive samples of Real-time RT-PCR were subjected to viral isolation. The results showed 3/12 samples positive for Real-time RT-PCR. 7/12 and 4/12 samples were positive for IgM and IgG against CHIKV respectively, two virus strains were isolated. Four viral genomes from Dongguan and Yangjiang were sequenced, characterized and phylogeneticly analyzed. Phylogenetic analysis revealed that the four seqeunced viruses had the closest relationship (99.4~99.6% identify) with the Singapore 2008 isolate belonging to the Indian ocean clade. A common mutation at the site of the E1-A226V was observed among four viruses. Four and three aa substitutions were detected in the CHIKV sequence from the Dongguan and Yangjiang outbreak strains respectively.

Conclusion

CHIKV with an E1-A226V mutation that originated from Southeast Asia isolates caused two outbreaks in China in 2010, and originated from two different infectious sources.
Multiscale perspectives of virus entry via endocytosis
Authors: Barrow Eric , Nicola Anthony V , Liu Jin
Published: June 2013

Most viruses take advantage of endocytic pathways to gain entry into host cells and initiate infections. Understanding of virus entry via endocytosis is critically important for the design of antiviral strategies. Virus entry via endocytosis is a complex process involving hundreds of cellular proteins. The entire process is dictated by events occurring at multiple time and length scales. In this review, we discuss and evaluate the available means to investigate virus endocytic entry, from both experimental and theoretical/numerical modeling fronts, and highlight the importance of multiscale features. The complexity of the process requires investigations at a systems biology level, which involves the combination of different experimental approaches, the collaboration of experimentalists and theorists across different disciplines, and the development of novel multiscale models.
Room temperature aqueous phase synthesis and characterization of novel nano-sized coordination polymers composed of copper(II), nickel(II), and zinc(II) metal ions with p-phenylenediamine (PPD) as the bridging ligand
Authors: Gupta Rimpy , Sanotra Sumit , Sheikh Haq Nawaz , Kalsotra Bansi Lal
Published: June 2013

Nanostructured metal-organic hybrid materials composed of nickel(II), copper(II), and zinc(II) metal ions and p-phenylenediamine (PPD) as the organic ligand were synthesized in aqueous medium at room temperature. The synthesized compounds were characterized by elemental analyses, powder X-ray diffraction (PXRD) spectra, Fourier transform infrared spectra, nuclear magnetic resonance (1H NMR) spectra, electronic spectra, scanning electron microscopy, N2 adsorption-desorption isotherm, and dynamic light scattering studies. N2 adsorption-desorption isotherm of copper(II)-PPD compound confirmed that it has mesoporous structure as it exhibits type-IV reversible isotherm with H1 hysterisis. Steep adsorption indicated that the mesopores possessing it are of uniform order. Barrett-Joyner-Halenda model showed an average pore diameter of 5.2 nm. The PXRD patterns of all the three compounds are identical and showed well-defined and highly intense diffraction peaks, thereby suggesting their nature as crystalline. The broadness of the diffraction peaks indicated that the particles are of nanometer dimensions.
Geophysics Bright Spots
Authors: Sun Yonghe
Published: June 2013

This is the last column of my two-year term as the coordinator for Bright Spots. I would like thank you for tracking the column and tracking new developments in Geophysics. I thank the editors for identifying Bright Spot papers, and thank Editor Tamas Nemeth for this enjoyable assignment. You might recall that we featured in the September-October column a paper by Gallardo et al. on integration of multiple geophysical data types (e.g., seismic and EM) using structure-coupled joint inversions. The authors applied a so-called “cross-gradient constraint” in the inversion. Such a constraint favors structural consistencies among the multiple types of model parameters. In the current issue of Geophysics, Lochbühler et al. present another application of structure-coupled inversion. Their twist is to impose a “structural similarity constraint” among different model parameter types for the joint inversion of geophysical (GPR) and hydrological data.
Glucocorticoid-Dependent Hippocampal Transcriptome in Male Rats: Pathway-Specific Alterations With Aging
Authors: Chen Kuey-Chu , Blalock Eric M. , Curran-Rauhut Meredith A. , Kadish Inga , Blalock Susan J. , Brewer Lawrence , Porter Nada M. , Landfield Philip W.
Published: June 2013

Although glucocorticoids (GCs) are known to exert numerous effects in the hippocampus, their chronic regulatory functions remain poorly understood. Moreover, evidence is inconsistent regarding the long-standing hypothesis that chronic GC exposure promotes brain aging/Alzheimer disease. Here, we adrenalectomized male F344 rats at 15 months of age, maintained them for 3 months with implanted corticosterone (CORT) pellets producing low or intermediate (glucocorticoid receptor–activating) blood levels of CORT, and performed microarray/pathway analyses in hippocampal CA1. We defined the chronic GC-dependent transcriptome as 393 genes that exhibited differential expression between intermediate and low CORT groups. Short-term CORT (4 days) did not recapitulate this transcriptome. Functional processes/pathways overrepresented by chronic CORT–up-regulated genes included learning/plasticity, differentiation, glucose metabolism, and cholesterol biosynthesis, whereas processes overrepresented by CORT–down-regulated genes included inflammatory/immune/glial responses and extracellular structure. These profiles indicate that GCs chronically activate neuronal/metabolic processes while coordinately repressing a glial axis of reactivity/inflammation. We then compared the GC transcriptome with a previously defined hippocampal aging transcriptome, revealing a high proportion of common genes. Although CORT and aging moved expression of some common genes in the same direction, the majority were shifted in opposite directions by CORT and aging (eg, glial inflammatory genes down-regulated by CORT are up-regulated with aging). These results contradict the hypothesis that GCs simply promote brain aging and also suggest that the opposite direction shifts during aging reflect resistance to CORT regulation. Therefore, we propose a new model in which aging-related GC resistance develops in some target pathways, whereas GC overstimulation develops in others, together generating much of the brain aging phenotype.
The effect of flow speed and body size on Kármán gait kinematics in rainbow trout
Authors: Akanyeti Otar , Liao James C.
Published: June 2013

We have little understanding of how fish hold station in unsteady flows. Here we investigate the effect of flow speed and body size on the kinematics of rainbow trout Kármán gaiting behind a 5 cm diameter cylinder. We establish a set of criteria revealing that not all fish positioned in a vortex street are Kármán gaiting. By far the highest probability of Kármán gaiting occurred at intermediate flow speeds between 30 and 70 cm s-1. We show that trout Kármán gait in a region of the cylinder wake where the velocity deficit is about 40% of the nominal flow. We observed that the relationships between certain kinematic and flow variables are largely preserved across flow speeds. Tail-beat frequency matches the measured vortex shedding frequency, which increases linearly with flow speed. Body wave speed is about 25% faster than the nominal flow velocity. At speeds where fish have a high probability of Kármán gaiting, body wavelength is about 25% longer than the cylinder wake wavelength. Likewise, the lateral (i.e. cross-stream) amplitude of the tail tip is about 50% greater than the expected lateral spacing of the cylinder vortices, while the body centre (BC) amplitude is about 70% less. Lateral COM acceleration increases quadratically with speed. Head angle decreases with flow speed. While these values are different from those found in fish swimming in uniform flow, the strategy for locomotion is the same; fish adjust to increasing flow by increasing their tail-beat frequency. Body size also plays a role in Kármán gaiting kinematics. Tail beat amplitudes of Kármán gaiting increase with body size, as in freestream swimming, but are almost three times larger in magnitude. Larger fish have a shorter body wavelength and slower body wave speed than smaller fish, which is a surprising result compared to freestream swimming, where body wavelength and wave speed increases with size. In contrast to freestream swimming, tail beat frequency for Kármán gaiting fish does not depend on the body size and is a function of the vortex shedding frequency.
Bilateral flight muscle activity predicts wing kinematics and 3-dimensional body orientation of locusts responding to looming objects
Authors: McMillan Glyn A. , Loessin Vicky , Gray John R.
Published: June 2013

We placed locusts in a wind tunnel using a loose tether design that allowed for motion in all three rotational degrees of freedom during presentation of a computer-generated looming disc. High-speed video allowed us to extract wing kinematics, abdomen position and 3-dimensional body orientation. Concurrent EMG recordings monitored bilateral activity from the first basalar depressor muscles (m97) of the forewings, which are implicated in flight steering. Behavioural responses to a looming disc included cessation of flight (wings folded over the body), glides and active steering during sustained flight in addition to a decrease and increase in wingbeat frequency prior to and during, respectively, an evasive turn. Active steering involved shifts in bilateral m97 timing, wing asymmetries, and whole body rotations in the yaw (ψ), pitch (χ), and roll (η) planes. Changes in abdomen position and hindwing asymmetries occurred after turns were initiated. Forewing asymmetry and changes in η were most highly correlated with m97 spike latency. Correlations also increased as the disc approached, peaking prior to collision. On the inside of a turn, m97 spikes occurred earlier relative to forewing stroke reversal and bilateral timing corresponded to forewing asymmetry as well as changes in whole body rotation. Double spikes in each m97 occurred most frequently at or immediately prior to the time the locusts turned, suggesting a behavioural significance. These data provide information on mechanisms underlying 3-dimensional flight manoeuvres and will be used to drive a closed loop flight simulator to study responses of motion-sensitive visual neurons during production of realistic behaviours.
A Simple Colorimetric Method for Detection of 16,17-Epoxyprogesterone
Authors: Jiang Dan , Tu Ran , Bai Peng , Wang Qinhong
Published: June 2013

As a steroidal drug intermediate, 16,17-epoxysterol plays an important role in pharmaceutical steroid synthesis. Current methods for epoxysterol determination normally require expensive equipment, are highly labor intensive, and are not suitable for a high-throughput system. Here we report an improved colorimetric assay with the potential to detect 16,17-epoxysterol at high throughput. The assay was developed by a colorimetric reaction using picric acid and validated in a 96-well microtiter plate format, which represents a simple and reliable assay for 16,17-epoxysterol. This method has a high potential application for the discovery of steroidal drugs.
Metallohydrogel Formed from Amphiphilic Pd Complex and α-Cyclodextrin: Control of Its Sol–Gel Transition
Authors: Taira Toshiaki , Suzaki Yuji , Osakada Kohtaro
Published: June 2013

Addition of α-cyclodextrin (α-CD) to amphiphilic Pd(II) complex with bipyridinium ligands forms the metal-containing rotaxane, and its aqueous solution undergoes sol–gel transition depending on the temperature and concentration.
From Nature to Fabrication: Biomimetic Design Principles for the Production of Complex Spatial Structures
Authors: Magna Riccardo La , Gabler Markus , Reichert Steffen , Schwinn Tobias , Waimer Frédéric , Menges Achim , Knippers Jan
Published: June 2013

In the current paper the authors present a biomimetic design methodology based on the analysis of the Echinoids (sea urchin and sand dollar) and the transfer of its structural morphology into a built full-scale prototype.

In the first part, an efficient wood jointing technique for planar sheets of wood through novel robotically fabricated finger-joints is introduced together with an investigation of the biological principles of plate structures and their mechanical features. Subsequently, the identified structural principles are translated and verified with the aid of a Finite Element Model, as well as a generative design system incorporating the rules and constraints of fabrication. The paper concludes with the presentation of a full-scale biomimetic prototype which integrates these morphological and mechanical principles to achieve an efficient and high-performing lightweight structure.