bluuebunny/crossref_metadata_2025 huggingface dataset:
Shikonin enhances efficacy of a gene-based cancer vaccine via induction of RANTES
Authors: Chen Hui-Ming , Wang Pi-Hsueh , Aravindaram Kandan , Chen Yun-Hsiang , Yu Hsiu-Hui , Yang Wen-Chin , Yang Ning-Sun
Published: April 2012

Background

Shikonin, a phytochemical purified fromLithospermum erythrorhizon, has been shown to confer diverse pharmacological activities, including accelerating granuloma formation, wound healing, anti-inflammation and others, and is explored for immune-modifier activities for vaccination in this study. Transdermal gene-based vaccine is an attractive approach for delivery of DNA transgenes encoding specific tumor antigens to host skin tissues. Skin dendritic cells (DCs), a potent antigen-presenting cell type, is known to play a critical role in transmitting and orchestrating tumor antigen-specific immunities against cancers. The present study hence employs these various components for experimentation.

Method

The mRNA and protein expression of RANTES were detected by RT-PCR and ELISA, respectively. The regional expression of RANTES and tissue damage in test skin were evaluated via immunohistochemistry assay. Fluorescein isothiocyanate sensitization assay was performed to trace the trafficking of DCs from the skin vaccination site to draining lymph nodes. Adjuvantic effect of shikonin on gene gun-delivered human gp100 (hgp100) DNA cancer vaccine was studied in a human gp100-transfected B16 (B16/hgp100) tumor model.

Results

Among various phytochemicals tested, shikonin induced the highest level of expression of RANTES in normal skin tissues. In comparison, mouse RANTES cDNA gene transfection induced a higher level of mRANTES expression for a longer period, but caused more extensive skin damage. Topical application of shikonin onto the immunization site before gene gun-mediated vaccination augmented the population of skin DCs migrating into the draining lymph nodes. A hgp100 cDNA gene vaccination regimen with shikonin pretreatment as an adjuvant in a B16/hgp100 tumor model increased cytotoxic T lymphocyte activities in splenocytes and lymph node cells on target tumor cells.

Conclusion

Together, our findings suggest that shikonin can effectively enhance anti-tumor potency of a gene-based cancer vaccine via the induction of RANTES expression at the skin immunization site.
PIntron: a fast method for detecting the gene structure due to alternative splicing via maximal pairings of a pattern and a text
Authors: Pirola Yuri , Rizzi Raffaella , Picardi Ernesto , Pesole Graziano , Della Vedova Gianluca , Bonizzoni Paola
Published: April 2012

Background

A challenging issue in designing computational methods for predicting the gene structure into exons and introns from a cluster of transcript (EST, mRNA) sequences, is guaranteeing accuracy as well as efficiency in time and space, when large clusters of more than 20,000 ESTs and genes longer than 1 Mb are processed. Traditionally, the problem has been faced by combining different tools, not specifically designed for this task.

Results

We propose a fast method based on ad hoc procedures for solving the problem. Our method combines two ideas: a novel algorithm of proved small time complexity for computing spliced alignments of a transcript against a genome, and an efficient algorithm that exploits the inherent redundancy of information in a cluster of transcripts to select, among all possible factorizations of EST sequences, those allowing to infer splice site junctions that are largely confirmed by the input data. The EST alignment procedure is based on the construction of maximal embeddings, that are sequences obtained from paths of a graph structure, called embedding graph, whose vertices are the maximal pairings of a genomic sequence T and an EST P. The procedure runs in time linear in the length of P and T and in the size of the output.

The method was implemented into the PIntron package. PIntron requires as input a genomic sequence or region and a set of EST and/or mRNA sequences. Besides the prediction of the full-length transcript isoforms potentially expressed by the gene, the PIntron package includes a module for the CDS annotation of the predicted transcripts.

Conclusions

PIntron, the software tool implementing our methodology, is available at http://www.algolab.eu/PIntron under GNU AGPL. PIntron has been shown to outperform state-of-the-art methods, and to quickly process some critical genes. At the same time, PIntron exhibits high accuracy (sensitivity and specificity) when benchmarked with ENCODE annotations.
Parametric modeling of cellular state transitions as measured with flow cytometry
Authors: Ho Hsiu J , Lin Tsung I , Chang Hannah H , Haase Steven B , Huang Sui , Pyne Saumyadipta
Published: April 2012

Background

Gradual or sudden transitions among different states as exhibited by cell populations in a biological sample under particular conditions or stimuli can be detected and profiled by flow cytometric time course data. Often such temporal profiles contain features due to transient states that present unique modeling challenges. These could range from asymmetric non-Gaussian distributions to outliers and tail subpopulations, which need to be modeled with precision and rigor.

Results

To ensure precision and rigor, we propose a parametric modeling framework StateProfiler based on finite mixtures of skewt-Normal distributions that are robust against non-Gaussian features caused by asymmetry and outliers in data. Further, we present in StateProfiler a new greedy EM algorithm for fast and optimal model selection. The parsimonious approach of our greedy algorithm allows us to detect the genuine dynamic variation in the key features as and when they appear in time course data. We also present a procedure to construct a well-fitted profile by merging any redundant model components in a way that minimizes change in entropy of the resulting model. This allows precise profiling of unusually shaped distributions and less well-separated features that may appear due to cellular heterogeneity even within clonal populations.

Conclusions

By modeling flow cytometric data measured over time course and marker space with StateProfiler, specific parametric characteristics of cellular states can be identified. The parameters are then tested statistically for learning global and local patterns of spatio-temporal change. We applied StateProfiler to identify the temporal features of yeast cell cycle progression based on knockout of S-phase triggering cyclins Clb5 and Clb6, and then compared the S-phase delay phenotypes due to differential regulation of the two cyclins. We also used StateProfiler to construct the temporal profile of clonal divergence underlying lineage selection in mammalian hematopoietic progenitor cells.
Expansion and diversification of the SET domain gene family following whole-genome duplications in Populus trichocarpa
Authors: Lei Li , Zhou Shi-Liang , Ma Hong , Zhang Liang-Sheng
Published: April 2012

Background

Histone lysine methylation modifies chromatin structure and regulates eukaryotic gene transcription and a variety of developmental and physiological processes. SET domain proteins are lysine methyltransferases containing the evolutionarily-conserved SET domain, which is known to be the catalytic domain.

Results

We identified 59 SET genes in the Populus genome. Phylogenetic analyses of 106 SET genes from Populus and Arabidopsis supported the clustering of SET genes into six distinct subfamilies and identified 19 duplicated gene pairs in Populus. The chromosome locations of these gene pairs and the distribution of synonymous substitution rates showed that the expansion of the SET gene family might be caused by large-scale duplications in Populus. Comparison of gene structures and domain architectures of each duplicate pair indicated that divergence took place at the 3'- and 5'-terminal transcribed regions and at the N- and C-termini of the predicted proteins, respectively. Expression profile analysis of Populus SET genes suggested that most Populus SET genes were expressed widely, many with the highest expression in young leaves. In particular, the expression profiles of 12 of the 19 duplicated gene pairs fell into two types of expression patterns.

Conclusions

The 19 duplicated SET genes could have originated from whole genome duplication events. The differences in SET gene structure, domain architecture, and expression profiles in various tissues of Populus suggest that members of the SET gene family have a variety of developmental and physiological functions. Our study provides clues about the evolution of epigenetic regulation of chromatin structure and gene expression.
Emergence of dengue virus 4 genotype II in Guangzhou, China, 2010: Survey and molecular epidemiology of one community outbreak
Authors: Jing Qin-Long , Yang Zhi-Cong , Luo Lei , Xiao Xin-Cai , Di Biao , He Peng , Fu Chuan-Xi , Wang Ming , Lu Jia-Hai
Published: April 2012

Background

The re-emergence of dengue virus 4 (DENV-4) has become a public health concern in South America, Southeast Asia and South Asia. However, it has not been known to have caused a local outbreak in China for the past 20 years. The purpose of this study was to elucidate the epidemiology of one local community outbreak caused by DENV-4 in Guangzhou city, China, in 2010; and to determine the molecular characteristics of the genotype II virus involved.

Case presentations

During September and October of 2010, one imported case, a Guangzhou resident who travelled back from Thailand, resulted in 18 secondary autochthonous cases in Guangzhou City, with an incidence rate of 5.53 per 10,000 residents. In indigenous cases, 14 serum samples tested positive for IgM against DENV and 7 for IgG from a total of 15 submitted serum samples, accompanied by 5 DENV-4 isolates. With identical envelope gene nucleotide sequences, the two isolates (D10168-GZ from the imported index case and Guangzhou 10660 from the first isolate in the autochthonous cases) were grouped into DENV-4 genotype II after comparison to 32 previous DENV-4 isolates from GenBank that originated from different areas.

Conclusions

Based on epidemiological and phylogenetic analyses, the outbreak, which was absent for 20 years after the DENV-4 genotype I outbreak in 1990, was confirmed as DENV-4 genotype II and initially traced to the imported index case, a Guangzhou resident who travelled back from Thailand.
Molecular monitoring of plasmodium falciparum drug susceptibility at the time of the introduction of artemisinin-based combination therapy in Yaoundé, Cameroon: Implications for the future
Authors: Menard Sandie , Morlais Isabelle , Tahar Rachida , Sayang Collins , Mayengue Pembe Issamou , Iriart Xavier , Benoit-Vical Françoise , Lemen Brigitte , Magnaval Jean-François , Awono-Ambene Parfait , Basco Leonardo K , Berry Antoine
Published: April 2012

Background

Regular monitoring of the levels of anti-malarial resistance of Plasmodium falciparum is an essential policy to adapt therapy and improve malaria control. This monitoring can be facilitated by using molecular tools, which are easier to implement than the classical determination of the resistance phenotype. In Cameroon, chloroquine (CQ), previously the first-line therapy for uncomplicated malaria was officially withdrawn in 2002 and replaced initially by amodiaquine (AQ) monotherapy. Then, artemisinin-based combination therapy (ACT), notably artesunate-amodiaquine (AS-AQ) or artemether-lumefantrine (AL), was gradually introduced in 2004. This situation raised the question of the evolution of P. falciparum resistance molecular markers in Yaoundé, a highly urbanized Cameroonian city.

Methods

The genotype of pfcrt 72 and 76 and pfmdr1 86 alleles and pfmdr1 copy number were determined using real-time PCR in 447 P. falciparum samples collected between 2005 and 2009.

Results

This study showed a high prevalence of parasites with mutant pfcrt 76 (83%) and pfmdr1 86 (93%) codons. On the contrary, no mutations in the pfcrt 72 codon and no samples with duplication of the pfmdr1 gene were observed.

Conclusion

The high prevalence of mutant pfcrt 76T and pfmdr1 86Y alleles might be due to the choice of alternative drugs (AQ and AS-AQ) known to select such genotypes. Mutant pfcrt 72 codon was not detected despite the prolonged use of AQ either as monotherapy or combined with artesunate. The absence of pfmdr1 multicopies suggests that AL would still remain efficient. The limited use of mefloquine or the predominance of mutant pfmdr1 86Y codon could explain the lack of pfmdr1 amplification. Indeed, this mutant codon is rarely associated with duplication of pfmdr1 gene. In Cameroon, the changes of therapeutic strategies and the simultaneous use of several formulations of ACT or other anti-malarials that are not officially recommended result in a complex selective pressure, rendering the prediction of the evolution of P. falciparum resistance difficult. This public health problem should lead to increased vigilance and regular monitoring.
Rate of vertical transmission of human papillomavirus from mothers to infants: Relationship between infection rate and mode of delivery
Authors: Park Hyun , Lee Si Won , Lee In Ho , Ryu Hyun Mee , Cho A Reum , Kang Young Soon , Hong Sung Ran , Kim Sung Soon , Seong Seok Ju , Shin Son Moon , Kim Tae Jin
Published: April 2012

Background

In contrast to consistent epidemiologic evidence of the role of sexual transmission of human papillomavirus (HPV) in adults, various routes may be related to HPV infection in infants. We have assessed the extent of HPV infection during the perinatal period, and the relationship between mode of delivery and vertical transmission.

Results

A total of 291 pregnant women over 36 weeks of gestation were enrolled with informed consent. Exfoliative cells were collected from maternal cervix and neonatal buccal mucosa. HPV infection and genotypes were determined with an HPV DNA chip, which can recognise 24 types. The HPV-positive neonates were re-evaluated 6 months after birth to identify the presence of persistent infection. HPV DNA was detected in 18.9 % (55/291) of pregnant women and 3.4 % (10/291) of neonates. Maternal infection was associated with abnormal cytology (p = 0.007) and primiparity (p = 0.015). The infected neonates were all born to HPV-positive mothers. The rate of vertical transmission was estimated at 18.2 % (10/55) which was positively correlated with maternal multiple HPV infection (p = 0.003) and vaginal delivery (p = 0.050), but not with labour duration and premature rupture of membranes. The rate of concordance of genotype was 100 % in mother-neonate pairs with vertical transmission. The neonatal HPV DNAs found at birth were all cleared at 6 months after delivery.

Conclusions

Vertical transmission of HPV DNA from HPV infected mother to the neonate increased when the infant was delivered through an infected cervix. However, the absence of persistent infection in infants at 6 months after delivery may suggest temporary inoculation rather than true vertical infection.
A Pilot study of the Sharing Risk Information Tool (ShaRIT) for Families with Hereditary Breast and Ovarian Cancer Syndrome
Authors: Kardashian Ani , Fehniger Julia , Creasman Jennifer , Cheung Eleanor , Beattie Mary Stanley
Published: April 2012

Background

Individuals who carry deleterious BRCA mutations face significantly elevated risks of breast, ovarian, and other cancers. These individuals are also responsible for informing relatives of their increased risk for carrying the family BRCA mutation. Few interventions have been developed to facilitate this family communication process.

Methods

We developed the Sharing Risk Information Tool (ShaRIT), a personalized educational intervention, to support BRCA carriers as they discuss BRCA positive results and their implications with relatives. We conducted a pilot study of 19 BRCA carriers identified through the University of California San Francisco Cancer Risk Program. Our study had two aims: 1) to assess the feasibility and acceptability of ShaRIT, and 2) describe characteristics associated with increased family communication and BRCA testing. Participants in our study were divided into two groups: those who had not received ShaRIT as part of their genetic counseling protocol (control group, n = 10) and those who received ShaRIT (n = 9).

Results

All 9 women who received ShaRIT reported that it was a useful resource. Characteristics associated with increased sharing and testing included: female gender, degree of relationship, and frequency of communication. Increased pedigree knowledge showed a trend toward higher rates of sharing.

Conclusions

Both participants and genetic counselors considered ShaRIT a well-received, comprehensive tool for disseminating individual risk information and clinical care guidelines to Hereditary Breast and Ovarian Cancer Syndrome families. Because of this, ShaRIT has been incorporated as standard of care at our institution. In the future we hope to evaluate the effects of ShaRIT on family communication and family testing in larger populations of BRCA positive families.
Socioeconomic inequalities in common mental disorders and psychotherapy treatment in the UK between 1991 and 2009
Authors: Jokela Markus , Batty G. David , Vahtera Jussi , Elovainio Marko , Kivimäki Mika
Published: April 2012

Background

Inequality in health and treatment of disease across socioeconomic status groups is a major public health issue.

Aims

To examine differences in socioeconomic status in common mental disorders and use of psychotherapy provided by the public and private sector in the UK between 1991 and 2009.

Method

During these years, 28 054 men and women responded to annual surveys by the nationally representative, population-based British Household Panel Survey (on average 7 measurements per participant; 207 545 person-observations). In each year, common mental disorders were assessed with the self-reported 12-item General Health Questionnaire and socioeconomic status was assessed on the basis of household income, occupational status and education.

Results

Higher socioeconomic status was associated with lower odds of common mental disorder (highest v. lowest household income quintile odds ratio (OR) 0.88, 95% CI 0.82–0.94) and of being treated by publicly provided psychotherapy (OR = 0.43, 95% CI 0.34–0.55), but higher odds of being a client of private psychotherapy (OR = 3.33, 95% CI 2.36–4.71). The status difference in publicly provided psychotherapy treatment was more pronounced at the end of follow-up (OR = 0.36, 95% CI 0.23–0.56, in 2005–2009) than at the beginning of the follow-up period (OR =0.96, 95% CI 0.66–1.39, in 1991–1994; time interaction P<0.001). The findings for occupational status and education were similar to those for household income.

Conclusions

The use of publicly provided psychotherapy has improved between 1991 and 2009 among those with low socioeconomic status, although social inequalities in common mental disorders remain.
The role of Edward Harrison's (1766–1838) disciples, Thomas Engall, John and George Epps, Charles Hoyland, John Evans Riadore, John Robinson and John Baptiste de Serney in the treatment of spinal deformity in the Victorian medical world
Authors: Bovine Gary , Silver John Russell , Weiner Marie-France
Published: April 2012

Edward Harrison was a distinguished and innovative physician, an educationalist who had a profound influence on the treatment of spinal deformities. He founded the first infirmary for the treatment of spinal diseases in London in 1837. Little is known of this institution but much of Harrison's legacy rests with his disciples who followed Harrison's principles of treatment to treat spinal deformity. Like Harrison they were unconventional individuals, influenced by religious beliefs and liberal political and social ideologies. After his death, initially they followed his methods of treatment but subsequently they were not afraid to pursue new forms of treatment including homeopathy at a time when traditional medicine had little to offer.
Victor Horsley (1857–1916) and the Temperance Movement
Authors: Dunnill Michael S
Published: April 2012

For nearly all of his life Victor Horsley campaigned against the evils of alcohol. This led him into direct conflict with politicians, brewers, publicans and the army. His views are of interest today when the subject of excessive consumption of alcohol is the subject of great public concern.
Radiological and clinical findings of 25 patients with invasive pulmonary aspergillosis: retrospective analysis of 2150 liver transplantation cases
Authors: Qin J , Fang Y , Dong Y , Zhu K , Wu B , An Y , Shan H
Published: April 2012

Objective: The purpose of this study was to evaluate the radiological and clinical findings of invasive pulmonary aspergillosis (IPA) after liver transplantation.

Methods: This study included 25 consecutive liver transplant recipients with histologically confirmed IPA after liver transplantation. Radiological examinations performed for diagnosis were available in all patients. Clinical findings and changes in clinical response and radiological findings after treatment were also evaluated.

Results: 3 main radiological findings were identified: nodules, 64% (16/25); masses, 36% (9/25); and consolidations in a patchy pattern, 20% (5/25). A tree-in-bud pattern was found in 12% (3/25) of patients. In 8 (32%) of 25 patients, we found a combination of 2 or more of these signs: 5 (20%) patients presented with concurrent nodules accompanied by patchy consolidations and/or tree-in-bud, and 3 (12%) patients showed masses accompanied by large consolidations. A halo sign was observed in 20 (80%) of 25 patients. Hypodense sign and cavitary lesions were encountered in 17 (68%) of 25 patients. Follow-up radiological findings after treatment showed improvement in 18 patients, no change in 4 patients and progression in 3 patients. There were three aspergillosis-associated deaths during the follow-up period. The onset time of IPA was a median of 31 days after transplantation. The most common symptom at diagnosis was fever (n=15). None of the 25 patients had leukopaenia at the time of the diagnosis of IPA.

Conclusions: The most common radiological findings of IPA after liver transplantation are multiple nodules with or without halo sign, masses and consolidations, which usually appear about 1 month after transplantation.
Imaging of muscle injury in the elite athlete
Authors: Lee J C , Mitchell A W M , Healy J C
Published: April 2012

Injuries to muscle in the elite athlete are common and may be responsible for prolonged periods of loss of competitive activity. The implications for the athlete and his/her coach and team may be catastrophic if the injury occurs at a critical time in the athlete's diary. Imaging now plays a crucial role in diagnosis, prognostication and management of athletes with muscle injuries. This article discusses the methods available to clinicians and radiologists that are used to assess skeletal muscle injury. The spectrum of muscle injuries sustained in the elite athlete population is both discussed and illustrated.
Stochastic Trust-Region Response-Surface Method (STRONG)—A New Response-Surface Framework for Simulation Optimization
Authors: Chang Kuo-Hao , Hong L. Jeff , Wan Hong
Published: April 2012

Response surface methodology (RSM) is a widely used method for simulation optimization. Its strategy is to explore small subregions of the decision space in succession instead of attempting to explore the entire decision space in a single attempt. This method is especially suitable for complex stochastic systems where little knowledge is available. Although RSM is popular in practice, its current applications in simulation optimization treat simulation experiments the same as real experiments. However, the unique properties of simulation experiments make traditional RSM inappropriate in two important aspects: (1) It is not automated; human involvement is required at each step of the search process; (2) RSM is a heuristic procedure without convergence guarantee; the quality of the final solution cannot be quantified. We propose the stochastic trust-region response-surface method (STRONG) for simulation optimization in attempts to solve these problems. STRONG combines RSM with the classic trust-region method developed for deterministic optimization to eliminate the need for human intervention and to achieve the desired convergence properties. The numerical study shows that STRONG can outperform the existing methodologies, especially for problems that have grossly noisy response surfaces, and its computational advantage becomes more obvious when the dimension of the problem increases.
Layered Graph Approaches to the Hop Constrained Connected Facility Location Problem
Authors: Ljubić Ivana , Gollowitzer Stefan
Published: April 2012

Given a set of customers, a set of potential facility locations, and some interconnection nodes, the goal of the connected facility location problem (ConFL) is to find the minimum-cost way of assigning each customer to exactly one open facility and connecting the open facilities via a Steiner tree. The sum of costs needed for building the Steiner tree, facility opening costs, and the assignment costs needs to be minimized. If the number of edges between a prespecified node (the so-called root) and each open facility is limited, we speak of the hop constrained facility location problem (HC ConFL). This problem is of importance in the design of data-management and telecommunication networks.

In this article we provide the first theoretical and computational study for this new problem that has not been studied in the literature so far. We propose two disaggregation techniques that enable the modeling of HC ConFL: (i) as a directed (asymmetric) ConFL on layered graphs, or (ii) as the Steiner arborescence problem (SA) on layered graphs. This allows for usage of best-known mixed integer programming models for ConFL or SA to solve the corresponding hop constrained problem to optimality. In our polyhedral study, we compare the obtained models with respect to the quality of their linear programming lower bounds. These models are finally computationally compared in an extensive computational study on a set of publicly available benchmark instances. Optimal values are reported for instances with up to 1,300 nodes and 115,000 edges.
Branch-and-Price Guided Search for Integer Programs with an Application to the Multicommodity Fixed-Charge Network Flow Problem
Authors: Hewitt Mike , Nemhauser George , Savelsbergh Martin W. P.
Published: April 2012

We develop an exact algorithm for integer programs that uses restrictions of the problem to produce high-quality solutions quickly. Column generation is used both for generating these problem restrictions and for producing bounds on the value of the optimal solution. The performance of the algorithm is greatly enhanced by using structure, such as arises in network flow type applications, to help define the restrictions that are solved. In addition, local search around the current best solution is incorporated to enhance overall performance. The approach is parallelized and computational experiments on a classical problem in network design demonstrate its efficacy.
Density and Dynamic Viscosity of Bovine Milk Affect by Temperature and Composition
Authors: Alcântara Lizzy Ayra Pereira , Fontan Rafael da Costa Ilhéu , Bonomo Renata Cristina Ferreira , Souza, Jr. Evaldo Cardozo de , Sampaio Vanessa Santos , Pereira Rúbner Gonçalves
Published: April 2012

In order to design and to adapt equipments for food processing, it is essential to know thermophysical properties. Once temperature and composition affects these properties, models based in such factors are important for further calculation. In this work, density and dynamic viscosity of bovine milk, probably the most processed food fluid in the world, were determined within large ranges of temperature and major constituents (moisture, fat, lactose, protein and minerals), based on typical processing values. Density varied from (962.01 to 1100.45) kg/m3 and dynamic viscosity varied from (0.60 to 63.70) mPa∙s. Temperature and moisture content negatively affected both properties, while lactose, protein and minerals contents positively affected them. An increase in fat content reduced density and increased dynamic viscosity. Experimental density data were fitted to the simplest multiple linear model and dynamic viscosity data were fitted to a multiple type Arrehnius’ model, obtaining good agreement.
Optogenetic electrophysiology: a new approach to combine cellular and systems physiology
Authors: Mishina Yukiko , Mutoh Hiroki , Knöpfel Thomas
Published: April 2012

Optogenetics is the latest new subdiscipline in brain sciences that merges optical imaging, protein engineering and genetic dissection of neuronal circuits to optically monitor and control brain activity with high spatial and temporal precision. In this review, the conceptual framework that fueled the development of this methodology is first introduced and the central tools utilized in monitoring and controlling of neuronal circuit elements using light are described. How this innovative approach fosters our understanding of both physiological and pathophysiological properties of brain networks is then discussed. Finally, the potential clinical application of optogenetic approaches is outlined.
Keratin function and regulation in tissue homeostasis and pathogenesis
Authors: Roth Wera , Hatzfeld Mechthild , Friedrich Maik , Thiering Sören , Magin Thomas M.
Published: April 2012

Epithelial tissues act as hubs in metabolism and communication and protect the organism against dehydration, infections, pharmacological and physical stress. Keratin intermediate filament proteins are well established as major cytoskeletal players in maintaining epithelial integrity. More recently, an involvement of keratins in growth control and organelle functions has emerged. Disruption of the keratin cytoskeleton by mutations or its reorganization following posttranslational modifications can render epithelia susceptible to tissue damage and various stresses, while loss of keratin expression is a hallmark of epithelial-mesenchymal transition (EMT). To understand the molecular mechanisms by which keratins perform their functions remains a formidable challenge. Based on selected examples, we will discuss how cell-specific expression of keratin isotypes affects cytoarchitecture and cell behavior. Further, we ask how posttranslational modifications alter keratin organization and interactions during signaling. Next, we discuss pathomechanisms of epidermal keratin disorders in the light of novel data. Finally, we raise open questions and point out future directives.
One-pot synthesis of fused 3,4-dihydropyrimidin-2(1H)-ones and thiones using a novel ionic liquid as an efficient and reusable catalyst: improved protocol conditions for the Biginelli-like scaffolds
Authors: Janardhan Banothu , Laxmi Somarapu Vijaya , Rajitha Bavanthu
Published: April 2012

A novel ionic liquid with multi-SO3H groups has been found to be an efficient acid catalyst for the one-pot three-component synthesis of fused 3,4-dihydropyrimidin-2(1H)-ones and thiones under solvent free conditions. Good yields, short reaction times, straight forward workup, reusability of the catalyst and green conditions are the most obvious advantages of this methodology.
Synthesis and growth regulatory activity of novel 5-(3-alkyl-4-methyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-3H-[1,3,4]thiadiazole(oxadiazole)-2-thiones and their derivatives
Authors: Knyazyan Aram , Eliazyan Karine , Pivazyan Vergush , Ghazaryan Emma , Harutyunyan Siranush , Yengoyan Aleksandr
Published: April 2012

Base- and acid-mediated heterocyclization of 2-(3-alkyl-4-methyl-2-thioxo-2,3-dihydro-thiazole-5-carbonyl)-hydrazinecarbodithioic acid potassium salts 3, 4 yielded the corresponding 3H-[1,3,4]thiadiazole(oxadiazole)-2-thiones 5–8. The reaction of these products with alkyl halides gave S-substituted derivatives 9–12. Treatment of oxadiazoles 7, 8with secondary amines furnished a mixture of cyclic and acyclic derivatives 13–16. The preliminary biological assay showed that the synthesized compounds could be of interest as growth stimulants.
A Proof of Catalan's Convolution Formula
Authors: Regev Alon
Published: April 2012

A new proof is given for the
Bone morphogenetic protein 6 promotes FSH receptor and anti-Müllerian hormone mRNA expression in granulosa cells from hen prehierarchal follicles
Authors: Ocón-Grove O M , Poole D H , Johnson A L
Published: April 2012

A growing body of literature provides evidence of a prominent role for bone morphogenetic proteins (BMPs) in regulating various stages of ovarian follicle development. Several actions for BMP6 have been previously reported in the hen ovary, yet only within postselection (preovulatory) follicles. The initial hypothesis tested herein is that BMP6 increases FSH receptor (FSHR) mRNA expression within the granulosa layer of prehierarchal (6–8 mm) follicles (6–8 GC). BMP6 mRNA is expressed at higher levels within undifferentiated (1–8 mm) follicles compared with selected (≥9 mm) follicles. Recombinant human (rh) BMP6 initiates SMAD1, 5, 8 signaling in cultured 6–8 GC and promotes FSHR mRNA expression in a dose-related fashion. In addition, a 21 h preculture with rhBMP6 followed by a 3 h challenge with FSH increases cAMP accumulation, STAR (StAR) expression, and progesterone production. Interestingly, rhBMP6 also increases expression of anti-Müllerian hormone (AMH) mRNA in cultured 6–8 GC. This related BMP family member has previously been implicated in negatively regulating FSH responsiveness during follicle development. Considering these data, we propose that among the paracrine and/or autocrine actions of BMP6 within prehierarchal follicles is the maintenance of both FSHR and AMH mRNA expression. We predict that before follicle selection, one action of AMH within granulosa cells from 6 to 8 mm follicles is to help suppress FSHR signaling and prevent premature granulosa cell differentiation. At the time of selection, we speculate that the yet undefined signal directly responsible for selection initiates FSH responsiveness. As a result, FSH signaling suppresses AMH expression and initiates the differentiation of granulosa within the selected follicle.
The sperm epigenome and potential implications for the developing embryo
Authors: Jenkins Timothy G , Carrell Douglas T
Published: April 2012

Recent work in the field of male fertility has yielded significant increases in our understanding of the sperm epigenome and its potential role in embryonic development. These new findings have enabled a broad classification of a normal epigenetic state in the male gamete and have provided insight into the possible etiologies of some idiopathic male infertility cases. Histone retention and modification, protamine incorporation into the chromatin, DNA methylation, and spermatozoal RNA transcripts appear to play important roles in the epigenetic state of mature sperm. These epigenetic factors may reveal a historical record of spermatogenesis, portend future functions in embryogenesis, and help to elucidate mechanism of pluripotency. In contrast to the once held dogma regarding the importance of the paternal epigenome, the unique epigenetic landscape in sperm appears to serve more than the gamete itself and is likely influential in the developing embryo. In fact, growing evidence suggests that mature sperm provide appropriate epigenetic marks that drive specific genes toward activation and contribute to the pluripotent state of the embryonic cells. Although not definitive, the current literature provides evidence for the role of the sperm epigenome in the embryo. Future work must be focused on the characterization of epigenetic abnormalities commonly found in individuals with compromised fertility to further establish this role. Additionally, studies should target the effects of environment and aging on the sperm epigenetic program and subsequent fertility loss to determine the etiology of aberrant epigenetic profiles.
Theoretical and experimental study of graphane-like materials
Authors: Ilyin A. M. , Nemkaeva R. R. , Guseinov N. R. , Tsyganov I. A.
Published: April 2012

Computer modeling and quantum-mechanical calculations were used for computational characterization of the energetic and structural properties of the graphane and graphane-like structures. Graphane-like fragments with various levels of hydrogenation were experimentally produced by mechanical exfoliation of multilayer highly oriented pyrolytic graphite preliminary doped electrolytically. Raman spectra showed the essential contribution of hydrogenated state and the correlation between the time of hydrogenation and the amplitudes of the peaks, related to “graphane-like” state.
Evaluation of hydrogen generation test using redox reaction
Authors: Hayashi Shoji , Asai Kenji , Nishizawa Naoki
Published: April 2012

The hydrogen energy society is desirable to mitigate global warming. The redox reaction of iron oxide Fe3O4 which can generate 4·8 wt% hydrogen for metallic iron is considered as one of means to store and supply it. However, this reaction is known to be significantly retarded because of sintering of solid particles. Toward solving these problems, our previous research proved alumina coating on the surface of fine iron oxide particles could improve the reaction efficiency most drastically. In this work, a lot of small pellets made of 1·25 mol% alumina coating fine particles Fe2O3 (0·1 μm dia.) by means of hydrometallurgy were prepared. Then, hydrogen generation using redox reaction in the packed bed of these pellets was tested under electric heating by gas chromatography of exit gas. Based on steam conversion degrees at 350°C with oxidation time after H2 reduction at 500°C, it was found that less steam flow rates in H2O-N2 oxidizing gas mixture (a constant N2 flow rate) provided higher steam conversion degrees near 100% and the theoretical total hydrogen generation degrees were mostly realized, independently of steam flow rates. The results were overall investigated with the view point of potential application to fuel cell.
Functional species pool framework to test for biotic effects on community assembly
Authors: de Bello Francesco , Price Jodi N. , Münkemüller Tamara , Liira Jaan , Zobel Martin , Thuiller Wilfried , Gerhold Pille , Götzenberger Lars , Lavergne Sébastien , Lepš Jan , Zobel Kristjan , Pärtel Meelis
Published: April 2012

Functional trait differences among species are increasingly used to infer the effects of biotic and abiotic processes on species coexistence. Commonly, the trait diversity observed within communities is compared to patterns simulated in randomly generated communities based on sampling within a region. The resulting patterns of trait convergence and divergence are assumed to reveal abiotic and biotic processes, respectively. However, biotic processes such as competition can produce both trait divergence and convergence, through either excluding similar species (niche differences, divergence) or excluding dissimilar species (weaker competitor exclusion, convergence). Hence, separating biotic and abiotic processes that can produce identical patterns of trait diversity, or even patterns that neutralize each other, is not feasible with previous methods. We propose an operational framework in which the functional trait dissimilarity within communities (FDcomm) is compared to the corresponding trait dissimilarity expected from the species pool (i.e., functional species pool diversity, FDpool). FDpool includes the set of potential species for a site delimited by the operating environmental and dispersal limitation filters. By applying these filters, the resulting pattern of trait diversity is consistent with biotic processes, i.e., trait divergence (FDcomm > FDpool) indicates niche differentiation, while trait convergence (FDcomm < FDpool) indicates weaker competitor exclusion. To illustrate this framework, with its potential application and constraints, we analyzed both simulated and field data. The functional species pool framework more consistently detected the simulated trait diversity patterns than previous approaches. In the field, using data from plant communities of typical Northern European habitats in Estonia, we found that both niche‐based and weaker competitor exclusion influenced community assembly, depending on the traits and community considered. In both simulated and field data, we demonstrated that only by estimating the species pool of a site is it possible to differentiate the patterns of trait dissimilarity produced by operating biotic processes. The framework, which can be applied with both functional and phylogenetic diversity, enables a reinterpretation of community assembly processes. Solving the challenge of defining an appropriate reference species pool for a site can provide a better understanding of community assembly.
Factors Affecting Burnout When Caring for Older Adults Needing Long Term Care Services in Korea
Authors: Won Seojin , Song Inuk
Published: April 2012

The purpose of this study was to address factors related to caregiver burnout as a result of caring for an older adult with a chronic disease. Characteristics of care recipients and caregivers as well as social support were included to identify the relationships with caregiver burnout. The analysis was based on a sample of 334 older adults and their caregivers in Korea. The logistic regression results indicated that the period of being in need of another's help among care-recipients, co-residence, caregivers' health condition, previous care experience, and caregivers' free time were correlated with the caregivers' future caregiving. Interestingly, the more experience caregivers had in caring for older adults, the more willing they were to provide care in the future. Thus, the discussion focuses on services for those who are new to providing care for older adults because they tend to have less coping skills.
Leisure as a Resource for Successful Aging by Older Adults with Chronic Health Conditions
Authors: Hutchinson Susan L. , Nimrod Galit
Published: April 2012

Drawing on the model of Selective Optimization with Compensation (SOC) (Baltes & Baltes, 1990), the purpose of this article is to examine leisure-related goals of older adults with chronic conditions and the strategies they use to not only successfully manage their chronic health conditions but live well with them. Semi-structured in-person interviews were conducted with 18 community-dwelling older adults (nine males, nine females, ages 58–87 years) with a variety of chronic conditions. Inductive and deductive within and cross-case thematic analyses resulted in descriptions of changes and continuity in participants' leisure participation following the onset of their chronic condition and construction of four themes: drawing on existing resources for continued involvement, setting leisure-based goals, using strategies to get more out of life, and more than managing: living a life of meaning. Implications for promoting successful aging are discussed, specifically the benefits of incorporating information and skill-building to help older adults recognize that leisure can be a resource for healthy aging and self-managing their chronic health condition.
Dairy welfare in Hungary and in the United Kingdom vs. National and European Union legislation
Authors: Gudaj R.T. , Brydl E. , Lehoczky J. , Komlósi I.
Published: April 2012

Dairy industries in Eastern and Western Europe have different history,
heritage, but the same aim to produce cheap, high quantity of good quality
milk with the care of dairy welfare. Member countries of European Union had
choice to either implement minimum standards provided by the European
Commission, like in Hungary, or to create their own legislation also covering
minimum standards, like in the Great Britain. British, Hungarian and European
Union legislation was compared with dairy welfare measures taken on 53 farms
in the UK and on 27 farms in Hungary. Among 13 welfare measures observed 8
were found to be statistically different (p<0.05. p<0.01 or p<0.001) between
countries. Fewer cows were reported with dirty hind limbs, hock hair losses,
non hock injuries, being dull or with greater flight distance on Hungarian
farms than in the UK. There were fewer cows with dirty udders, being fat or
lame in the UK in comparison to Hungarian farms. Cheaper bedding materials in
Hungary are thought to be the major factors cows are found cleaner. More farm
workers per one animal make more attention is paid for providing cattle with
suitable conditions for resting what also might impact shorter flight
distance. In the Great Britain cleaner udders might be related to modern
husbandry systems providing cleaner conditions. Education is also thought to
be playing a great role in lower proportion of cows being lame, with
digestion problems and mastitis in the UK in comparison to Hungary.
Role of SLC11A1 gene in disease resistance
Authors: Thomas N. , Joseph S.
Published: April 2012

Genetic improvement in livestock was achieved earlier by selective breeding
of individuals with superior phenotypes. Now due to the advances in molecular
genetics and biotechnology candidate genes of economic traits can be included
in selection for breeding programmes. Genes responsible for the
resistance/susceptibility to infections with various pathogens (Major Histo
Compatibility (MHC) genes, Solute Carrier family11 member A1 (SLC11A1) gene,
Toll Like Receptor (TLR) genes etc.), have been recently identified and
characterized in human beings as well as in many animals. Among these the
role of SLC11A1 gene is very important due to its association with
resistance/ susceptibility to various intracellular pathogens in human as
well as in livestock species. The SLC11A1 gene, formerly known as natural
resistance-associated macrophage protein 1 (NRAMP1) encodes an integral
membrane protein regulating the activity of macrophages. Genetic resistance/
susceptibility to diseases due to candidate gene polymorphisms could be used
in selection and breeding for disease resistance in animals.
Laser induced backside wet and dry etching of solar glass by short pulse ytterbium fiber laser irradiation
Authors: Chao He , Furong Liu , Min Wang , Jianwen Yuan , Jimin Chen
Published: April 2012

Microstructures fabricated on the surface of solar glass have the potential to improve the performance of solar cells. In this paper, in order to overcome the high transmittance to 1064 nm center wavelength fiber laser irradiation and realize high efficiency process on transparent glass substrates, different absorber materials, including alumina powder, alumina ceramic wafers, and copper sulphate solutions, were applied for dry and wet etching under the irradiation of 1064 nm pulsed fiber laser respectively. The laser fluence was varied from 7 to 10 J/cm2 with a pulse repetition rate of 20 kHz. The morphology of trenches etched by means of laser induced backside dry etching (LIBDE) and by laser induced backside wet etching was measured using a scanning electronic scope, and compared from the aspects of etch depth and width, as well as the roughness. On the basis of this comparison, a higher etch rate can easily be obtained by dry etching, while lower roughness is a feature of wet etching. The mechanism of LIBDE of solar glass was investigated by demonstrating the procedure of dry etching using alumina ceramic wafer. Moreover, the etch threshold fluence was estimated to be 7.47 J/cm2 by extrapolation. Both types of laser induced backside etching techniques, wet and dry, show the evidence of effective microprocessing on solar glass.