bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current advances in the treatment of Alzheimer's disease: focused on considerations targeting Aβ and tau
Authors: Hong-Qi Yang , Zhi-Kun Sun , Sheng-Di Chen 
Published: October 2012

Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder that impairs mainly the memory and cognitive function in elderly. Extracellular beta amyloid deposition and intracellular tau hyperphosphorylation are the two pathological events that are thought to cause neuronal dysfunction in AD. Since the detailed mechanisms that underlie the pathogenesis of AD are still not clear, the current treatments are those drugs that can alleviate the symptoms of AD patients. Recent studies have indicated that these symptom-reliving drugs also have the ability of regulating amyloid precursor protein processing and tau phosphorylation. Thus the pharmacological mechanism of these drugs may be too simply-evaluated. This review summarizes the current status of AD therapy and some potential preclinical considerations that target beta amyloid and tau protein are also discussed.
Transdifferentiation of MALME-3M and MCF-7 Cells toward Adipocyte-like Cells is Dependent on Clathrin-mediated Endocytosis
Authors: Carcel-Trullols Jaime , Aguilar-Gallardo Cristóbal , Garcia-Alcalde Fernando , Pardo-Cea Miguel Angel , Dopazo Joaquin , Conesa Ana , Simón Carlos 
Published: October 2012

AbstractEnforced cell transdifferentiation of human cancer cells is a promising alternative to conventional chemotherapy. We previously identified albumin-associated lipid- and, more specifically, saturated fatty acid-induced transdifferentiation programs in human cancer cells (HCCLs). In this study, we further characterized the adipocyte-like cells, resulting from the transdifferentiation of human cancer cell lines MCF-7 and MALME-3M, and proposed a common mechanistic approach for these transdifferentiating programs. We showed the loss of pigmentation in MALME-3M cells treated with albumin-associated lipids, based on electron microscopic analysis, and the overexpression of perilipin 2 (PLIN2) by western blotting in MALME-3M and MCF-7 cells treated with unsaturated fatty acids. Comparing the gene expression profiles of naive melanoma MALME-3M cells and albumin-associated lipid-treated cells, based on RNA sequencing, we confirmed the transcriptional upregulation of some key adipogenic gene markers and also an alternative splicing of the adipogenic master regulator PPARG, that is probably related to the reported up regulated expression of the protein. Most importantly, these results also showed the upregulation of genes responsible for Clathrin (CLTC) and other adaptor-related proteins. An increase in CLTC expression in the transdifferentiated cells was confirmed by western blotting. Inactivation of CLTC by chlorpromazine (CHP), an inhibitor of CTLC mediated endocytosis (CME), and gene silencing by siRNAs, partially reversed the accumulation of neutral lipids observed in the transdifferentiated cells. These findings give a deeper insight into the phenotypic changes observed in HCCL to adipocyte-like transdifferentiation and point towards CME as a key pathway in distinct transdifferentiation programs.DisclosuresSimon C and Aguilar-Gallardo C are co-inventors of the International Patent Application No. PCT/EP2011/004941 entitled “Methods for tumor treatment and adipogenesis differentiation”.
An iterative scheme for numerical solution of Volterra integral equations using collocation method and Chebyshev polynomials
Authors: Rashidinia Jalil , Najafi Esmaeil , Arzhang Asghar 
Published: October 2012

AbstractAbstractWhen we discretize nonlinear Volterra integral equations using some numerical, such as collocation methods, the arising algebraic systems are nonlinear. Applying quasilinear technique to the nonlinear Volterra integral equations gives raise to linear Volterra integral equations. The solutions of these equations yield a functional sequence quadratically convergent to the solution. Then, we use collocation method based on Chebyshev polynomials and a modified Clenshaw-Curtis quadrature and obtain a numerical solution. Error analysis has been performed, and the method has been applied on three numerical examples.
Selective gene-expression profiling of migratory tumor cells in vivo predicts clinical outcome in breast cancer patients
Authors: Patsialou Antonia , Wang Yarong , Lin Juan , Whitney Kathleen , Goswami Sumanta , Kenny Paraic A , Condeelis John S 
Published: October 2012

Abstract
Introduction
Metastasis of breast cancer is the main cause of death in patients. Previous genome-wide studies have identified gene-expression patterns correlated with cancer patient outcome. However, these were derived mostly from whole tissue without respect to cell heterogeneity. In reality, only a small subpopulation of invasive cells inside the primary tumor is responsible for escaping and initiating dissemination and metastasis. When whole tissue is used for molecular profiling, the expression pattern of these cells is masked by the majority of the noninvasive tumor cells. Therefore, little information is available about the crucial early steps of the metastatic cascade: migration, invasion, and entry of tumor cells into the systemic circulation.

Methods
In the past, we developed an in vivo invasion assay that can capture specifically the highly motile tumor cells in the act of migrating inside living tumors. Here, we used this assay in orthotopic xenografts of human MDA-MB-231 breast cancer cells to isolate selectively the migratory cell subpopulation of the primary tumor for gene-expression profiling. In this way, we derived a gene signature specific to breast cancer migration and invasion, which we call the Human Invasion Signature (HIS).

Results
Unsupervised analysis of the HIS shows that the most significant upregulated gene networks in the migratory breast tumor cells include genes regulating embryonic and tissue development, cellular movement, and DNA replication and repair. We confirmed that genes involved in these functions are upregulated in the migratory tumor cells with independent biological repeats. We also demonstrate that specific genes are functionally required for in vivo invasion and hematogenous dissemination in MDA-MB-231, as well as in patient-derived breast tumors. Finally, we used statistical analysis to show that the signature can significantly predict risk of breast cancer metastasis in large patient cohorts, independent of well-established prognostic parameters.

Conclusions
Our data provide novel insights into, and reveal previously unknown mediators of, the metastatic steps of invasion and dissemination in human breast tumors in vivo. Because migration and invasion are the early steps of metastatic progression, the novel markers that we identified here might become valuable prognostic tools or therapeutic targets in breast cancer.
Vascular endothelial growth factor receptor-1 mRNA overexpression in peripheral blood as a useful prognostic marker in breast cancer
Authors: Kosaka Yoshimasa , Kataoka Akemi , Yamaguchi Hiroshi , Ueo Hiroaki , Akiyoshi Sayuri , Sengoku Norihiko , Kuranami Masaru , Ohno Shinji , Watanabe Masahiko , Mimori Koshi , Mori Masaki 
Published: October 2012

Abstract
Introduction
Identification of useful markers associated with poor prognosis in breast cancer patients is critically needed. We previously showed that expression of vascular endothelial growth factor receptor-1 mRNA in peripheral blood may be useful to predict distant metastasis in gastric cancer patients. However, expression of vascular endothelial growth factor receptor-1 mRNA in peripheral blood of breast cancer patients has not yet been studied.

Methods
Real-time reverse transcriptase-PCR was used to analyze vascular endothelial growth factor receptor-1 mRNA expression status with respect to various clinical parameters in 515 patients with breast cancer and 25 controls.

Results
Expression of vascular endothelial growth factor receptor-1 mRNA in peripheral blood was higher in breast cancer patients than in controls. Increased vascular endothelial growth factor receptor-1 mRNA expression was associated with large tumor size, lymph node metastasis and clinical stage. Patients with high vascular endothelial growth factor receptor-1 mRNA expression also experienced a poorer survival rate than those with low expression levels, including those patients with triple-negative type and luminal-HER2(-) type disease.

Conclusions
Expression of vascular endothelial growth factor receptor-1 mRNA in peripheral blood may be useful for prediction of poor prognosis in breast cancer, especially in patients with triple-negative type and luminal-HER2(-) type disease.
Sex hormone changes during weight loss and maintenance in overweight and obese postmenopausal African-American and non-African-American women
Authors: Stolzenberg-Solomon Rachael Z , Falk Roni T , Stanczyk Frank , Hoover Robert N , Appel Lawrence J , Ard Jamy D , Batch Bryan C , Coughlin Janelle , Han Xu , Lien Lillian F , Pinkston Christina M , Svetkey Laura P , Katki Hormuzd A 
Published: October 2012

Abstract
Introduction
Changes in sex hormones with weight loss might have implications for breast cancer prevention but have not been examined extensively, particularly in African-American (AA) women.

Methods
We conducted a prospective study of 278 overweight/obese postmenopausal women (38% AA) not taking hormone therapy within the Weight Loss Maintenance Trial. All participants lost at least 4 kg after a 6-month weight-loss phase and attempted to maintain weight loss during the subsequent 12 months. We evaluated the percentage changes in estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate and sex hormone-binding globulin (SHBG) using generalized estimating equations.

Results
In all study phases, AA women had higher levels of estrogen and testosterone concentrations, independent of adiposity. On average, participants lost 7.7 kg during the weight-loss phase, and concentrations of estrone (-5.7%, P = 0.006), estradiol (-9.9%, P <0.001), free estradiol (-13.4%, P <0.0001), and free testosterone (-9.9%, P <0.0001) decreased, while the SHBG concentration (16.2%, P <0.001) increased. Weight change did not significantly affect total testosterone or other androgen concentrations. Compared with non-AA women, AA women experienced less change in estrogens per kilogram of weight change (that is, per 1 kg weight loss: estrone, -0.6% vs. -1.2%, P-interaction = 0.10; estradiol, -1.1% vs. -1.9%, P-interaction = 0.04; SHBG, 0.9% vs. 1.6%, P-interaction = 0.006; free estradiol, -1.4% vs. -2.1%, P-interaction = 0.01).

Conclusion
To the best of our knowledge this is the first study to examine and compare the effects of intentional weight loss and maintenance on a panel of sex hormones in AA women and non-AA women. Although speculative, these data suggest hormonal differences may contribute to different racial patterns of breast cancer incidence and mortality and encourage further investigations to understand the long-term effects of weight loss on sex hormones in obese postmenopausal women.

Trial Registration
ClinicalTrials.gov: NCT00054925
Medical-grade honey does not reduce skin colonization at central venous catheter-insertion sites of critically ill patients: a randomized controlled trial
Authors: Kwakman Paulus H , Müller Marcella C , Binnekade Jan M , van den Akker Johannes P , de Borgie Corianne A , Schultz Marcus J , Zaat Sebastian A 
Published: October 2012

Abstract
Introduction
Catheter-related bloodstream infections (CRBSIs) associated with short-term central venous catheters (CVCs) in intensive care unit (ICU) patients are a major clinical problem. Bacterial colonization of the skin at the CVC insertion site is an important etiologic factor for CRBSI. The aim of this study was to assess the efficacy of medical-grade honey in reducing bacterial skin colonization at insertion sites.

Methods
A prospective, single-center, open-label randomized controlled trial was performed at the ICU of a university hospital in The Netherlands to assess the efficacy of medical-grade honey to reduce skin colonization of insertion sites. Medical-grade honey was applied in addition to standard CVC-site dressing and disinfection with 0.5% chlorhexidine in 70% alcohol. Skin colonization was assessed on a daily basis before CVC-site disinfection. The primary end point was colonization of insertion sites with >100 colony-forming units at the last sampling before removal of the CVC or transfer of the patient from the ICU. Secondary end points were quantitative levels of colonization of the insertion sites and colonization of insertion sites stratified for CVC location.

Results
Colonization of insertion sites was not affected by the use of medical-grade honey, as 44 (34%) of 129 and 36 (34%) of 106 patients in the honey and standard care groups, respectively, had a positive skin culture (P = 0.98). Median levels of skin colonization at the last sampling were 1 (0 to 2.84) and 1 (0 to 2.70) log colony-forming units (CFUs)/swab for the honey and control groups, respectively (P = 0.94). Gender, days of CVC placement, CVC location, and CVC type were predictive for a positive skin culture. Correction for these variables did not change the effect of honey on skin-culture positivity.

Conclusions
Medical-grade honey does not affect colonization of the skin at CVC insertion sites in ICU patients when applied in addition to standard disinfection with 0.5% chlorhexidine in 70% alcohol.

Trial registration
Netherlands Trial Registry, NTR1652.
Highly efficient bi-allelic mutation rates using TALENs in Xenopus tropicalis
Authors: Ishibashi Shoko , Cliffe Rebecca , Amaya Enrique 
Published: October 2012

Summary
In the past decade, Xenopus tropicalis has emerged as a powerful new amphibian genetic model system, which offers all of the experimental advantages of its larger cousin, Xenopus laevis. Here we investigated the efficiency of transcription activator-like effector nucleases (TALENs) for generating targeted mutations in endogenous genes in X. tropicalis. For our analysis we targeted the tyrosinase (oculocutaneous albinism IA) (tyr) gene, which is required for the production of skin pigments, such as melanin. We injected mRNA encoding TALENs targeting the first exon of the tyr gene into two-cell-stage embryos. Surprisingly, we found that over 90% of the founder animals developed either partial or full albinism, suggesting that the TALENs induced bi-allelic mutations in the tyr gene at very high frequency in the F0 animals. Furthermore, mutations tyr gene were efficiently transmitted into the F1 progeny, as evidenced by the generation of albino offspring. These findings have far reaching implications in our quest to develop efficient reverse genetic approaches in this emerging amphibian model.
Cell culture andDrosophilamodel systems define three classes of anaplastic lymphoma kinase mutations in neuroblastoma
Authors: Chand Damini , Yamazaki Yasuo , Ruuth Kristina , Schönherr Christina , Martinsson Tommy , Kogner Per , Attiyeh Edward F. , Maris John , Morozova Olena , Marra Marco A. , Ohira Miki , Nakagawara Akira , Sandström Per-Erik , Palmer Ruth H. , Hallberg Bengt 
Published: October 2012

SummaryNeuroblastoma is a childhood extracranial solid tumor which is associated with a number of genetic changes. Included in these genetic alterations are mutations in the kinase domain of the Anaplastic Lymphoma Kinase (ALK) receptor tyrosine kinase (RTK), which have been found in both somatic and familial neuroblastoma. In order to treat patients accordingly required characterisation of these mutations in terms of their response to ALK tyrosine kinase inhibitors (TKIs). Here, we report the identification and characterisation of two novel neuroblastoma ALK mutations (A1099T and 1464STOP) which we have investigated together with several previously reported but uncharacterised ALK mutations (T1087I, D1091N, T1151M, M1166R, F1174I and A1234T). In order to understand the potential role of these ALK mutations in neuroblastoma progression we have employed cell culture based systems together with the model organism Drosophila as a readout for ligand-independent activity. Mutation of ALK at position 1174 (F1174I) generates a gain-of-function receptor capable of activating intracellular targets, such as ERK (extracellular signal regulated kinase) and STAT3 (signal transducer and activator of transcription 3) in a ligand independent manner. Analysis of these previously uncharacterised ALK mutants and comparison with ALKF1174 mutants suggests that ALK mutations observed in neuroblastoma fall into three classes. These are: (i) gain-of-function ligand independent mutations such as ALKF1174, (ii) kinase-dead ALK mutants, e.g. ALKI1250T(Schonherr et al 2011a) or (iii) ALK mutations which are ligand-dependent in nature. Irrespective of the nature of the observed ALK mutants, in every case the activity of the mutant ALK receptors could be abrogated by the ALK inhibitor crizotinib (PF-02341066, Xalkori), albeit with differing levels of sensitivity.
Leukocyte migration from a fish eye's view
Authors: Deng Qing , Huttenlocher Anna 
Published: October 2012

Summary
In the last five years, the zebrafish (Danio rerio) has rapidly gained popularity as a model system for studying leukocyte migration and trafficking in vivo. The optical clarity of zebrafish embryos, as well as the potential for genetic manipulation and the development of tools for live imaging, have provided new insight into how leukocytes migrate in response to directional cues in live animals. This Commentary discusses recent progress in our understanding of how leukocytes migrate in vivo, including the role of intracellular signaling through phosphatidylinositol 3-kinase (PI3K) in both random and directed migration. The importance of leukocyte reverse migration in the resolution of inflammation will also be discussed. Finally, we will highlight how zebrafish models have helped to provide new insight into leukocyte migration and the way in which migration is altered in disease.
Bioorganic Studies on the Key Natural Products from Venomous Mammals and Marine Invertebrates
Authors: Kita Masaki 
Published: October 2012

Abstract
The discovery of new bioactive molecules, facilitated by a deeper understanding of nature, will advance our knowledge of biological processes and lead to new strategies to treat disease. Recent technological advancements including spectroscopic analyses and genetic approaches have provided outstanding opportunities for new discoveries, even in the case of scarce, unstable, and composite compounds. This account summarizes two recent aspects of bioorganic chemistry: mammalian venoms and antitumor marine macrolides. Due to the interesting ecology of venomous mammals, we examined the constituents of mammalian venom, and identified unique neurotoxic peptides and kallikrein-like proteases in shrews and platypus. The present findings may lead to the development of valuable vasoactive or pain-relief agents, and to a deeper understanding of the biological evolution of vertebrates in relation to toxic substances. We have also established the target proteins and mode of actions of aplyronine A, a potent antitumor and apoptogenic marine macrolide. The complexity and diversity of actin-targeting natural products might enable them to achieve multiple interactions with as-yet-unidentified biomacromolecules, such as cytoskeleton proteins and focal adhesion proteins, which should offer better perspectives for the design and development of new antitumor drugs.
„Mein Leben gleicht einem Roman …“: Kants Schüler Friedrich August Hahnrieder und seine Geschichte
Authors: Krouglov Alexei N. 
Published: October 2012

Abstract
The life story of Kant’s student F. A. Hahnrieder (1765/6–1829) provides us with new examples of the application of the categorical imperative. Kant has given his opinion about that. The biography of Hahnrieder suggests that Kant has not always insisted on the uniqueness of the interpretation of the categorical imperative. He has also admitted other, “paradoxical”, “unusual”, but not “fantastic” interpretations. Kant has even respected a radical interpretation of the categorical imperative. On the base of the archive data, numerous mistakes about Hahnrieder were corrected in biographies of Kant and in the Akademie-Ausgabe.
Inferences of Demography and Selection in an African Population of Drosophila melanogaster
Authors: Singh Nadia D , Jensen Jeffrey D , Clark Andrew G , Aquadro Charles F 
Published: October 2012

Abstract
It remains a central problem in population genetics to infer the past action of natural selection, and these inferences pose a challenge because demographic events will also substantially affect patterns of polymorphism and divergence. Thus it is imperative to explicitly model the underlying demographic history of the population whenever making inferences about natural selection. In light of the considerable interest in adaptation in African populations of Drosophila melanogaster, which are considered ancestral to the species, we generated a large polymorphism data set representing 2.1 Mb from each of 20 individuals from a Ugandan population of D. melanogaster. In contrast to previous inferences of a simple population expansion in eastern Africa, our demographic modeling of this ancestral population reveals a strong signature of a population bottleneck followed by population expansion, which has significant implications for future demographic modeling of derived populations of this species. Taking this more complex underlying demographic history into account, we also estimate a mean X-linked region-wide rate of adaptation of 6 × 10−11/site/generation and a mean selection coefficient of beneficial mutations of 0.0009. These inferences regarding the rate and strength of selection are largely consistent with most other estimates from D. melanogaster and indicate a relatively high rate of adaptation driven by weakly beneficial mutations.
Large Neurological Component to Genetic Differences Underlying Biased Sperm Use in Drosophila
Authors: Chow Clement Y , Wolfner Mariana F , Clark Andrew G 
Published: October 2012

Abstract
Sperm competition arises as a result of complex interactions among male and female factors. While the roles of some male factors are known, little is known of the molecules or mechanisms that underlie the female contribution to sperm competition. The genetic tools available for Drosophila allow us to identify, in an unbiased manner, candidate female genes that are critical for mediating sperm competition outcomes. We first screened for differences in female sperm storage and use patterns by characterizing the natural variation in sperm competition in a set of 39 lines from the sequenced Drosophila Genetic Reference Panel (DGRP) of wild-derived inbred lines. We found extensive female variation in sperm competition outcomes. To generate a list of candidate female genes for functional studies, we performed a genome-wide association mapping, utilizing the common single-nucleotide polymorphisms (SNPs) segregating in the DGRP lines. Surprisingly, SNPs within ion channel genes and other genes with roles in the nervous system were among the top associated SNPs. Knockdown studies of three candidate genes (para, Rab2, and Rim) in sensory neurons innervating the female reproductive tract indicate that some of these candidate female genes may affect sperm competition by modulating the neural input of these sensory neurons to the female reproductive tract. More extensive functional studies are needed to elucidate the exact role of all these candidate female genes in sperm competition. Nevertheless, the female nervous system appears to have a previously unappreciated role in sperm competition. Our results indicate that the study of female control of sperm competition should not be limited to female reproductive tract-specific genes, but should focus also on diverse biological pathways.