bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-dependent roles of peroxisomes in the hippocampus of a transgenic mouse model of Alzheimer’s disease
Authors: Fanelli Francesca , Sepe Sara , D’Amelio Marcello , Bernardi Cinzia , Cristiano Loredana , Cimini AnnaMaria , Cecconi Francesco , Ceru' Maria Paola , Moreno Sandra 
Published: February 2013

Abstract

Background
Alzheimer’s Disease (AD) is a progressive neurodegenerative disease, especially affecting the hippocampus. Impairment of cognitive and memory functions is associated with amyloid β-peptide-induced oxidative stress and alterations in lipid metabolism. In this scenario, the dual role of peroxisomes in producing and removing ROS, and their function in fatty acids β-oxidation, may be critical. This work aims to investigating the possible involvement of peroxisomes in AD onset and progression, as studied in a transgenic mouse model, harboring the human Swedish familial AD mutation. We therefore characterized the peroxisomal population in the hippocampus, focusing on early, advanced, and late stages of the disease (3, 6, 9, 12, 18 months of age). Several peroxisome-related markers in transgenic and wild-type hippocampal formation were comparatively studied, by a combined molecular/immunohistochemical/ultrastructural approach.

Results
Our results demonstrate early and significant peroxisomal modifications in AD mice, compared to wild-type. Indeed, the peroxisomal membrane protein of 70 kDa and acyl-CoA oxidase 1 are induced at 3 months, possibly reflecting the need for efficient fatty acid β-oxidation, as a compensatory response to mitochondrial dysfunction. The concomitant presence of oxidative damage markers and the altered expression of antioxidant enzymes argue for early oxidative stress in AD. During physiological and pathological brain aging, important changes in the expression of peroxisome-related proteins, also correlating with ongoing gliosis, occur in the hippocampus. These age- and genotype-based alterations, strongly dependent on the specific marker considered, indicate metabolic and/or numerical remodeling of peroxisomal population.

Conclusions
Overall, our data support functional and biogenetic relationships linking peroxisomes to mitochondria and suggest peroxisomal proteins as biomarkers/therapeutic targets in pre-symptomatic AD.
Role of infectious agents in the carcinogenesis of brain and head and neck cancers
Authors: Alibek Kenneth , Kakpenova Ainur , Baiken Yeldar 
Published: February 2013

AbstractThis review concentrates on tumours that are anatomically localised in head and neck regions. Brain cancers and head and neck cancers together account for more than 873,000 cases annually worldwide, with an increasing incidence each year. With poor survival rates at late stages, brain and head and neck cancers represent serious conditions. Carcinogenesis is a multi-step process and the role of infectious agents in this progression has not been fully identified. A major problem with such research is that the role of many infectious agents may be underestimated due to the lack of or inconsistency in experimental data obtained globally. In the case of brain cancer, no infection has been accepted as directly oncogenic, although a number of viruses and parasites are associated with the malignancy. Our analysis of the literature showed the presence of human cytomegalovirus (HCMV) in distinct types of brain tumour, namely glioblastoma multiforme (GBM) and medulloblastoma. In particular, there are reports of viral protein in up to 100% of GBM specimens. Several epidemiological studies reported associations of brain cancer and toxoplasmosis seropositivity. In head and neck cancers, there is a distinct correlation between Epstein-Barr virus (EBV) and nasopharyngeal carcinoma (NPC). Considering that almost every undifferentiated NPC is EBV-positive, virus titer levels can be measured to screen high-risk populations. In addition there is an apparent association between human papilloma virus (HPV) and head and neck squamous cell carcinoma (HNSCC); specifically, 26% of HNSCCs are positive for HPV. HPV type 16 was the most common type detected in HNSCCs (90%) and its dominance is even greater than that reported in cervical carcinoma. Although there are many studies showing an association of infectious agents with cancer, with various levels of involvement and either a direct or indirect causative effect, there is a scarcity of articles covering the role of infection in carcinogenesis of brain and head and neck cancers. We review recent studies on the infectious origin of these cancers and present our current understanding of carcinogenic mechanisms, thereby providing possible novel approaches to cancer treatment.
The zebrafish mutants for the V-ATPase subunits d, ac45, E, H and c and their variable pigment dilution phenotype
Authors: Ramos-Balderas Jose L , Carrillo-Rosas Samantha , Guzman Aida , Navarro Rosa E , Maldonado Ernesto 
Published: February 2013

Abstract

Background
The V-ATPase is a proton pump that creates an acidic medium, necessary for lysosome function and vesicular traffic. It is also essential for several developmental processes. Many enzymes, like the V-ATPase, are assemblies of multiple subunits, in which each one performs a specific function required to achieve full activity. In the zebrafish V-ATPase 15 different subunits form this multimeric complex and mutations in any of these subunits induce hypopigmentation or pigment dilution phenotype. We have previously found variability in the pigment dilution phenotype among five of the V-ATPase zebrafish mutants. This work presents additional information about such differences and is an update from a previous report.

Findings
We describe the variable phenotype severity observed among zebrafish V-ATPase pigment dilution mutants studying mRNA expression levels from their corresponding genes. At the same time we carried out phylogenetic analysis for this genes.

Conclusions
Based in the similarities between different pigment dilution mutants we suggest that there is an essential role for V-ATPases in melanosome biogenesis and melanocyte survival. Neither variable expression levels for the different V-ATPase subunits studied here or the presence of duplicated genes seems to account for the variable phenotype severity from this group of mutants. We believe there are some similarities between the pigment dilution phenotype from zebrafish V-ATPase insertional mutants and pigment mutants obtained in a chemical screening (“Tubingen pigmentation mutants”). As for some of these “Tubingen mutants” the mutated gene has not been found we suggest that mutations in V-ATPase genes may be inducing their defects.
Can otoplasty impact hearing? A prospective randomized controlled study examining the effects of pinna position on speech reception and intelligibility
Authors: McNeil Michael L , Aiken Steve J , Bance Manohar , Leadbetter Jeff R , Hong Paul 
Published: February 2013

Objectives Otoplasty is a commonly performed surgical procedure that restores the ideal position of the pinna. Although the pinna is a well-recognized component of the auditory apparatus, no studies have assessed the audiological effects of this procedure. We sought to quantify the impact of pinna repositioning on speech intelligibility and reception. Methods Eighteen adults with normal hearing and pinnae were recruited and the pinna positions were randomized in each participant. Intracanal acoustical analysis was performed to calculate the Speech Intelligibility Index (SII). Hearing In Noise Test (HINT) with two azimuth speaker arrangement was also performed. The outcome measures were compared using paired; t-tests for both pinna positions. Results The SII significantly improved with the pinna in forward position (49.3 vs. 45.8, p<0.001). HINT thresholds also improved with the pinna forward (-6.43dB vs. -5.08dB, p=0.0003). Conclusions Pinna position affects audiological performance, in both speech intelligibility and speech reception in noise. These are novel findings that may impact the informed consent process and decision to treat for patients undergoing otoplasty.
Fibrolipoma of the nasal septum; report of the first case
Authors: Ozturk Murat , Ila Kadri , Kara Ahmet , Iseri Mete 
Published: February 2013

Background/Objective Fibrolipomas are a rare subtype of lipomas and very rare in the oral and maxillofacial region. Lipomas affecting the central nervous system are even more infrequent occurring with a frequency of 0.1%. Study design, methods Case report. Case presentation This report includes a patient who had a nasal septal fibrolipoma and an accompanying corpus callosum lipoma. Conclusions To our knowledge, this is the first reported nasal septal fibrolipoma case in the literature. The diagnostic and surgical features of this case and the unity of septal fibrolipoma and intracranial lipomas are discussed.
The constant beat: cardiomyocytes adapt their forces by equal contraction upon environmental stiffening
Authors: Hersch Nils , Wolters Benjamin , Dreissen Georg , Springer Ronald , Kirchgeßner Norbert , Merkel Rudolf , Hoffmann Bernd 
Published: February 2013

Summary
Cardiomyocytes are responsible for the permanent blood flow by coordinated heart contractions. This vital function is accomplished over a long period of time with almost the same performance, although heart properties, as its elasticity, change drastically upon aging or as a result of diseases like myocardial infarction. In this paper we have analyzed late rat embryonic heart muscle cells' morphology, sarcomere/costamere formation and force generation patterns on substrates of various elasticities ranging from ∼1 to 500 kPa, which covers physiological and pathological heart stiffnesses. Furthermore, adhesion behaviour, as well as single myofibril/sarcomere contraction patterns, was characterized with high spatial resolution in the range of physiological stiffnesses (15 kPa to 90 kPa). Here, sarcomere units generate an almost stable contraction of ∼4%. On stiffened substrates the contraction amplitude remains stable, which in turn leads to increased force levels allowing cells to adapt almost instantaneously to changing environmental stiffness. Furthermore, our data strongly indicate specific adhesion to flat substrates via both costameric and focal adhesions. The general appearance of the contractile and adhesion apparatus remains almost unaffected by substrate stiffness.
Motor neurons and glia exhibit specific individualized responses to TDP-43 expression in a Drosophila model of amyotrophic lateral sclerosis
Authors: Estes Patricia S. , Daniel Scott G. , Mccallum Abigail P. , Boehringer Ashley V. , Sukhina Alona S. , Zwick Rebecca A. , Zarnescu Daniela C. 
Published: February 2013

Summary
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by complex neuronal and glial phenotypes. Recently, RNA-based mechanisms have been linked to ALS via RNA-binding proteins such as TDP-43, which has been studied in vivo using models ranging from yeast to rodents. We have developed a Drosophila model of ALS based on TDP-43 that recapitulates several aspects of pathology, including motor neuron loss, locomotor dysfunction and reduced survival. Here we report the phenotypic consequences of expressing wild-type and four different ALS-linked TDP-43 mutations in neurons and glia. We show that TDP-43-driven neurodegeneration phenotypes are dose- and age-dependent. In motor neurons, TDP-43 appears restricted to nuclei, which are significantly misshapen due to mutant but not wild-type protein expression. In glia and in the developing neuroepithelium, TDP-43 associates with cytoplasmic puncta. TDP-43-containing RNA granules are motile in cultured motor neurons, although wild-type and mutant variants exhibit different kinetic properties. At the neuromuscular junction, the expression of TDP-43 in motor neurons versus glia leads to seemingly opposite synaptic phenotypes that, surprisingly, translate into comparable locomotor defects. Finally, we explore sleep as a behavioral readout of TDP-43 expression and find evidence of sleep fragmentation consistent with hyperexcitability, a suggested mechanism in ALS. These findings support the notion that although motor neurons and glia are both involved in ALS pathology, at the cellular level they can exhibit different responses to TDP-43. In addition, our data suggest that individual TDP-43 alleles utilize distinct molecular mechanisms, which will be important for developing therapeutic strategies.
Transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development in aXenopusmodel
Authors: Chernet Brook T. , Levin Michael 
Published: February 2013

SummaryUnderstanding mechanisms that orchestrate cell behavior into appropriately patterned tissues and organs within the organism is an essential element of preventing, detecting and treating cancer. Bioelectric signals (resting transmembrane voltage potential gradients in all cells) underlie an important and broadly conserved set of control mechanisms that regulate pattern formation. We tested the role of transmembrane potential in tumorigenesis mediated by canonical oncogenes in Xenopus laevis. Depolarized membrane potential (Vmem) was a characteristic of induced tumor-like structures (ITLSs) generated by overexpression of Gli1, KrasG12D, Xrel3 or p53Trp248. This bioelectric signature was also present in precursor ITLS sites. Vmem is a bioelectric marker that reveals ITLSs before they become histologically and morphologically apparent. Moreover, voltage was functionally important: overexpression of hyperpolarizing ion transporters caused a return to normal Vmem and significantly reduced ITLS formation in vivo. To characterize the molecular mechanism by which Vmem change regulates ITLS phenotypes, we performed a suppression screen. Vmem hyperpolarization was transduced into downstream events via Vmem-regulated activity of SLC5A8, a sodium-butyrate exchanger previously implicated in human cancer. These data indicate that butyrate, a histone deacetylase (HDAC) inhibitor, might be responsible for transcriptional events that mediate suppression of ITLSs by hyperpolarization. Vmem is a convenient cellular parameter by which tumors induced by human oncogenes can be detected in vivo and represents a new diagnostic modality. Moreover, control of resting membrane potential is functionally involved in the process by which oncogene-bearing cells depart from normal morphogenesis programs to form tumors. Modulation of Vmem levels is a novel and promising strategy for tumor normalization.
Endothelial cell and model membranes respond to shear stress by rapidly decreasing the order of their lipid phases
Authors: Yamamoto Kimiko , Ando Joji 
Published: February 2013

Summary
Endothelial cells (ECs) sense shear stress and transduce blood flow information into functional responses that play important roles in vascular homeostasis and pathophysiology. A unique feature of shear-stress-sensing is the involvement of many different types of membrane-bound molecules, including receptors, ion channels and adhesion proteins, but the mechanisms remain unknown. Because cell membrane properties affect the activities of membrane-bound proteins, shear stress might activate various membrane-bound molecules by altering the physical properties of EC membranes. To determine how shear stress influences the cell membrane, cultured human pulmonary artery ECs were exposed to shear stress and examined for changes in membrane lipid order and fluidity by Laurdan two-photon imaging and FRAP measurements. Upon shear stress stimulation, the lipid order of EC membranes rapidly decreased in an intensity-dependent manner, and caveolar membrane domains changed from the liquid-ordered state to the liquid-disordered state. Notably, a similar decrease in lipid order occurred when the artificial membranes of giant unilamellar vesicles were exposed to shear stress, suggesting that this is a physical phenomenon. Membrane fluidity increased over the entire EC membranes in response to shear stress. Addition of cholesterol to ECs abolished the effects of shear stress on membrane lipid order and fluidity and markedly suppressed ATP release, which is a well-known EC response to shear stress and is involved in shear-stress Ca2+ signaling. These findings indicate that EC membranes directly respond to shear stress by rapidly decreasing their lipid phase order and increasing their fluidity; these changes could be linked to shear-stress-sensing and response mechanisms.
Depletion of PtdIns(4,5)P2 underlies retinal degeneration in Drosophila trp mutants
Authors: Sengupta Sukanya , Barber Thomas R. , Xia Hongai , Ready Donald F. , Hardie Roger C. 
Published: February 2013

Summary
The prototypical transient receptor potential (TRP) channel is the major light-sensitive, and Ca2+-permeable channel in the microvillar photoreceptors of Drosophila. TRP channels are activated following hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] by the key effector enzyme phospholipase C (PLC). Mutants lacking TRP channels undergo light-dependent retinal degeneration, as a consequence of the reduced Ca2+ influx. It has been proposed that degeneration is caused by defects in the Ca2+-dependent visual pigment cycle, which result in accumulation of toxic phosphorylated metarhodopsin–arrestin complexes (MPP–Arr2). Here we show that two interventions, which prevent accumulation of MPP–Arr2, namely rearing under red light or eliminating the C-terminal rhodopsin phosphorylation sites, failed to rescue degeneration in trp mutants. Instead, degeneration in trp mutants reared under red light was rescued by mutation of PLC. Degeneration correlated closely with the light-induced depletion of PtdIns(4,5)P2 that occurs in trp mutants due to failure of Ca2+-dependent inhibition of PLC. Severe retinal degeneration was also induced in the dark in otherwise wild-type flies by overexpression of a bacterial PtdInsPn phosphatase (SigD) to deplete PtdIns(4,5)P2. In degenerating trp photoreceptors, phosphorylated Moesin, a PtdIns(4,5)P2-regulated membrane–cytoskeleton linker essential for normal microvillar morphology, was found to delocalize from the rhabdomere and there was extensive microvillar actin depolymerisation. The results suggest that compromised light-induced Ca2+ influx, due to loss of TRP channels, leads to PtdIns(4,5)P2 depletion, resulting in dephosphorylation of Moesin, actin depolymerisation and disintegration of photoreceptor structure.
The ER Ca2+ sensor STIM1 regulates actomyosin contractility of migratory cells
Authors: Chen Ying-Ting , Chen Yih-Fung , Chiu Wen-Tai , Wang Yang-Kao , Chang Hsien-Chang , Shen Meng-Ru 
Published: February 2013

Summary
Stromal interaction molecule 1 (STIM1) is an endoplasmic reticulum (ER) Ca2+ sensor that triggers the store-operated Ca2+ entry (SOCE). The clinical relevance of STIM1 has been highlighted in breast and cervical cancer, but the molecular mechanism by which STIM1 promotes cancer progression remains unclear. This study explores the regulatory mechanisms by which STIM1-dependent Ca2+ signaling controls cancer cell migration. Three different SOCE inhibitors, SKF96365, 2-APB and YM-58483, significantly inhibited cervical cancer cell migration to a similar extent to that of STIM1 silencing. In contrast, STIM1 overexpression significantly enhanced cervical cancer cell migration. Live cell confocal images and three-dimensional tomograms showed that STIM1 formed aggregates and translocated towards the plasma membranes of migratory cells, and this was accompanied by increasing cytosolic Ca2+ spikes. STIM1 silencing also inhibited the recruitment and association of active focal adhesion kinase (pTyr397-FAK) and talin at focal adhesions, indicating the blockade of force transduction from integrin signaling. Epidermal growth factor-induced phosphorylation of myosin II regulatory light chains was abolished by STIM1 knockdown and SOCE inhibition. Dual immunostaining of activated myosin II (pSer19-MLC) and actin revealed that actomyosin formation depended on STIM1-mediated Ca2+ entry. Most importantly, STIM1 expression levels as well as SOCE activity controlled the generation of cell contractile force, as measured by the microfabricated post-array-detector system. These results highlight the unique role of STIM1-dependent Ca2+ signaling in controlling cell migration by the regulation of actomyosin reorganization in conjunction with enhanced contractile forces.
Rapid Removal of o-Phthalaldehyde from Water by Polyallylamine-Conjugated Thermoresponsive Polymer-Mediated Extraction
Authors: Saitoh Tohru , Fukushima Kotaro , Hiraide Masataka 
Published: February 2013

Abstract
A high-level disinfectant, o-phthalaldehyde (OPA), was rapidly removed from water by a thermoresponsive polymer-mediated extraction using polyallylamine-conjugated poly(N-isopropylacrylamide). The use of 1 g of the thermoresponsive polymer allowed nearly complete removal of 130 mg of OPA.
F–CN Bond Cleavage by Iron Silyl Complex and Electronic Effect of the Group or Atom Attached to Cyano Group: A Theoretical DFT Study
Authors: Dahy AbdelRahman A , Koga Nobuaki 
Published: February 2013

Abstract
The cleavage of F–CN bond in the presence of Fe(II) silyl complex, [Cp(CO)FeSiMe3], was studied using density functional theory calculations and compared with the mechanisms for E–CN (E = C, N, and O) bond cleavages, which have previously been clarified to be a silyl-migration-induced reaction.
Synthesis of Water-Soluble Cyclophane Pentamers Using Click Chemistry as a Multivalent Host for Daunorubicin and Doxorubicin
Authors: Hayashida Osamu , Nakamura Yuki 
Published: February 2013

Abstract
Cationic cyclophane pentamer 1 has been prepared from a tetraazide-functionalized cyclophane derivative and four acetylene-functionalized cyclophane derivatives by Cu(I)-catalyzed 1,3-dipolar cycloadditions (click chemistry) in a 87% yield, followed by a treatment with trifluoroacetic acid. Cationic host 1 showed effective guest-binding behavior toward fluorescent guests such as 6-p-toluidinonaphthalene-2-sulfonate, in comparison with those of monomeric cyclophane. On the other hand, anionic cyclophane pentamer 2, which was derived from 1 by a reaction with succinic anhydride, showed enhanced guest-binding affinity toward anticancer drugs such as daunorubicin hydrochloride, in comparison with those of the monomeric cyclophane.
A Simple Synthetic Route for the Preparation of Tetramethylglycolide from Lactic Acid
Authors: Watanabe Kohtaro , Andou Yoshito , Shirai Yoshihito , Nishida Haruo 
Published: February 2013

Abstract
Poly(tetramethylglycolide), a chemical recyclable polymer, is currently attracting a lot of interest as a substitute for poly(l-lactic acid). We report here a simple and convenient route for the synthesis of tetramethylglycolide (TMG) from lactic acid. This method involves three steps: (1) one-step protection of lactic acid by cyclic acetalization employing acetone; (2) α-methylation of the obtained 2,2,5-trimethyl-1,3-dioxolan-4-one; and (3) one-pot synthesis of TMG including the hydrolysis of 2,2,5,5-tetramethyl-1,3-dioxolan-4-one. We found significant advantages of the incorporation of existing reactions in the synthesis of TMG.
Molecular Iodine in Aqueous Ammonia: Oxidative Fragmentation of Oxiranes to Nitriles
Authors: Jadhav Ravindra R , Akamanchi Krishnacharya G 
Published: February 2013

Abstract
Oxiranes undergo oxidative fragmentation, when treated with iodine in aqueous ammonia, to give nitriles. The reaction goes via formation of 1,2-amino alcohols as intermediates followed by C–C bond cleavage. Advantages of the method are use of off-the-shelf nonexplosive, unlike previously used potentially explosive o-iodoxybenzoic acid, reagents, mild reaction conditions, and easy work-up procedure.