bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of catalytically active matrix metalloproteinase‐1 in dermal fibroblasts induces collagen fragmentation and functional alterations that resemble aged human skin
Authors: Xia Wei , Hammerberg Craig , Li Yong , He Tianyuan , Quan Taihao , Voorhees John J. , Fisher Gary J. 
Published: April 2013

SummaryIncreased expression of matrix metalloproteinase‐1 (MMP‐1) and reduced production of type I collagen by dermal fibroblasts are prominent features of aged human skin. We have proposed that MMP‐1‐mediated collagen fibril fragmentation is a key driver of age‐related decline of skin function. To investigate this hypothesis, we constructed, characterized, and expressed constitutively active MMP‐1 mutant (MMP‐1 V94G) in adult human skin in organ culture and fibroblasts in three‐dimensional collagen lattice cultures. Expression of MMP‐1 V94G in young skin in organ culture caused fragmentation and ultrastructural alterations of collagen fibrils similar to those observed in aged human skin in vivo. Expression of MMP‐1 V94G in dermal fibroblasts cultured in three‐dimensional collagen lattices caused substantial collagen fragmentation, which was markedly reduced by MMP‐1 siRNA‐mediated knockdown or MMP inhibitor MMI270. Importantly, fibroblasts cultured in MMP‐1 V94G‐fragmented collagen lattices displayed many alterations observed in fibroblasts in aged human skin, including reduced cytoplasmic area, disassembled actin cytoskeleton, impaired TGF‐β pathway, and reduced collagen production. These results support the concept that MMP‐1‐mediated fragmentation of dermal collagen fibrils alters the morphology and function of dermal fibroblasts and provide a foundation for understanding specific mechanisms that link collagen fibril fragmentation to age‐related decline of fibroblast function.
Reducing signs of aging and increasing lifespan by drug synergy
Authors: Huang Xinhe , Liu Jun , Withers Bradley R. , Samide Aaron J. , Leggas Markos , Dickson Robert C. 
Published: April 2013

SummaryDisease incidence rises rapidly with age and increases both human suffering and economic hardship while shortening life. Advances in understanding the signaling pathways and cellular processes that influence aging support the possibility of reducing the incidence of age‐related diseases and increasing lifespan by pharmacological intervention. Here, we demonstrate a novel pharmacological strategy that both reduces signs of aging in the budding yeast Saccharomyces cerevisiae and generates a synergistic increase in lifespan. By combining a low dose of rapamycin, to reduce activity of the target of rapamycin complex 1 (TORC1) protein kinase, and myriocin, to reduce sphingolipid synthesis, we show enhancement of autophagy, genomic stability, mitochondrial function, and AMP kinase pathway activity. These processes are controlled by evolutionarily conserved signal transduction pathways that are vital for maintaining a healthy state and promoting a long life. Thus, our data show that it ought to be possible to find pharmacological approaches to generate a synergistic reduction in the incidence of human age‐related diseases to improve health quality in the elderly and enhance lifespan.
DSM‐5 criteria for depression with mixed features: a farewell to mixed depression
Authors: Koukopoulos A. , Sani G. 
Published: April 2013

ObjectiveTo review the DSM‐5 proposed criteria for mixed depression in light of robust and consistent historical and scientific evidence.MethodAn extensive historical search, a systematic review of the papers used by DSM‐5 as reference papers, and a PubMed search were performed.ResultsAs Hippocrates, depressive mixed states have been described as conditions of intense psychic suffering, consisting of depressed mood, inner tension, restlessness, and aimless psychomotor agitation. In DSM‐5, new criteria are proposed for a mixed features specifier, as part of depression either in major depressive disorder (MDD) or bipolar disorder. Those criteria require, as diagnostically specific, manic/hypomanic symptoms that are the least common kinds of symptoms that actually arise in depressive mixed states. The DSM‐5 proposal is based, almost entirely, on a speculative wish to avoid ‘overlapping’ manic and depressive symptoms. Mixed states are, in fact, nothing but overlapping manic and depressive symptoms.ConclusionIn this article, we review the psychopathology and research on mixed depressive states, and try to demonstrate that the DSM‐5 proposal has weak scientific basis and does not identify a large number of mixed depressive states. This may be harmful because of the different treatment required by these conditions.
Long‐term biometric optic components of diode laser‐treated threshold retinopathy of prematurity at 9 years of age
Authors: Yang Chang‐Sue , Wang An‐Guor , Shih Yung‐Feng , Hsu Wen‐Ming 
Published: April 2013

Abstract.Purpose:  To assess quantitatively the biometric optic components and its relationship with refractive status in preterm school children with diode laser‐treated threshold retinopathy of prematurity (ROP).Methods:  A prospective, cross‐sectional study in which ultrasound biometric measurement of optic components and cycloplegic refraction were performed on 24 consecutive preterm children with diode laser‐treated threshold ROP at the age of 9 years. The study results were compared with 1021 age‐matched full‐term control children from a national survey.Results:  The eyes with laser‐treated ROP showed statistically significantly thicker lens (3.94 versus 3.39 mm), steeper vertical corneal curvature (7.47 versus 7.67 mm) and shallower anterior chamber depth (ACD) (2.91 versus 3.58 mm) than age‐matched full‐term controls, but no difference in axial length (23.32 versus 23.24 mm). The laser‐treated eyes had a mean spherical equivalent (SE) of −4.49 D compared with mean SE of −0.44 D in controls. Of 46 eyes studied, 93% of eyes were myopic and 28.3% with high myopia (<−6.0 D) compared with the 32% prevalence of myopia in controls. In preterm children, younger gestational age tended to correlate with shallower ACD (r = 0.352) and thicker lens (r = −0.298); lower birth weight tended to correlate with shallower ACD (r = 0.372) and steeper cornea (r = 0.360).Conclusions:  There were higher prevalence and greater magnitude of myopia in preterm children. The significantly thicker lens, steeper corneal curvature and shallower anterior chamber depth are the major factors contributing to the development of myopia in preterm school children with laser‐treated threshold ROP.
Design, Synthesis, and Biological Evaluation of Catecholamine Vehicle for Studying Dopaminergic System
Authors: Singh Pooja , Kumar Vikas , Aggarwal Swati , Tiwari Anjani K. , Chuttani Krishna , Pratap Ramendra , Mishra Anil K. 
Published: April 2013

Catecholamine mimetic EDTA‐bis(tyramide) was synthesized and characterized by various spectroscopic techniques (NMR, mass spectroscopy) and λem 310 nm for the excitation at 270 nm. Molecular docking studies were performed with human serum albumin (PDB 1E78), showing binding pattern with amino acid residues Arg218, Arg222, and Lys444, identifies the ligand‐human serum albumin interaction for the transportation affinity of the ligand at the specific site of the target. Subsequently, binding study with human serum albumin at λex = 350 nm found to be 5.847 × 104 m−1 shows effective quenching effect. Additionally, to go more insight, acetylcholinesterase binding affinity was investigated, which shows 90% binding affinity for the 10 mm concentration. IC50 value was found 18.60 μm for MAO‐B inhibition. Finally, EDTA‐bis(tyramide) labeled with 99mTc to investigate its in vivo radiopharmaceutical efficiency having 97% binding affinity with 98% radiochemical purity. In vivo studies were carried out for 99mTc‐EDTA‐bis(tyramide) included blood kinetics showed a quick wash out from the circulation via renal route, and biodistribution revealed that maximum %ID/g was found in kidney at 1 h, and its scintigraphy image shows 3.96% brain uptake with respect to whole body.
Physicochemical and Biological Characterization of Pep‐1/Elastin Complexes
Authors: Ahmad Nasrollahi Saman , Taghibiglou Changiz , Fouladdel Shamileh , Dinarvand Rasoul , Moosavi Movahedi Ali A. , Azizi Ebrahim , Farboud Effat S. 
Published: April 2013

Transdermal drug delivery of proteins is challenging because the skin acts as a natural and protective barrier. Several techniques including using the cell‐penetrating peptides have been studied to increase the penetration of therapeutic proteins into and through the skin. Cell‐penetrating peptides facilitate and improve the transduction of large and hydrophilic cargo molecules through plasma membrane. We have recently reported an efficient skin delivery of elastin protein in complex with a cell‐penetrating peptide called Pep‐1. As the biophysical characteristics of cell‐penetrating peptide/protein complexes have been linked with their biological responses, in this study, we investigated biophysical properties of Pep‐1/elastin complexes (ratio 10:1) stored in three temperatures (−20 °C, 4 °C and 25 °C) by photon correlation spectroscopy, circular dichroism and isothermal denaturation. We also evaluated the ability of transduction of this complex into cells and skin tissue using both fluorescence microscopy and Kodak In‐Vivo FX Pro Imaging System.
The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy
Authors: Marshall Jamie L. , Kwok Yukwah , McMorran Brian J. , Baum Linda G. , Crosbie‐Watson Rachelle H. 
Published: April 2013

Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin– and utrophin–glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein‐replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein–protein interactions amongst the adhesion complexes and is an important potential therapeutic target. Here, we review current protein‐replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic.
The adaptive immune response does not influence hantavirus disease or persistence in the Syrian hamster
Authors: Prescott Joseph , Safronetz David , Haddock Elaine , Robertson Shelly , Scott Dana , Feldmann Heinz 
Published: April 2013

SummaryPathogenic New World hantaviruses cause severe disease in humans characterized by a vascular leak syndrome, leading to pulmonary oedema and respiratory distress with case fatality rates approaching 40%. Hantaviruses infect microvascular endothelial cells without conspicuous cytopathic effects, indicating that destruction of the endothelium is not a mechanism of disease. In humans, high levels of inflammatory cytokines are present in the lungs of patients that succumb to infection. This, along with other observations, suggests that disease has an immunopathogenic component. Currently the only animal model available to study hantavirus disease is the Syrian hamster, where infection with Andes virus (ANDV), the primary agent of disease in South America, results in disease that closely mimics that seen in humans. Conversely, inoculation of hamsters with a passaged Sin Nombre virus (SNV), the virus responsible for most cases of disease in North America, results in persistent infection with high levels of viral replication. We found that ANDV elicited a stronger innate immune response, whereas SNV elicited a more robust adaptive response in the lung. Additionally, ANDV infection resulted in significant changes in the blood lymphocyte populations. To determine whether the adaptive immune response influences infection outcome, we depleted hamsters of CD4+ and CD8+ T cells before infection with hantaviruses. Depletion resulted in inhibition of virus‐specific antibody responses, although the pathogenesis and replication of these viruses were unaltered. These data show that neither hantavirus replication, nor pathogenesis caused by these viruses, is influenced by the adaptive immune response in the Syrian hamster.
Numerical chromosome disorders in the common marmoset (Callithrix jacchus) – comparison between two captive colonies
Authors: Delimitreva S. , Wedi E. , Bakker J. , Tkachenko O.Y. , Nikolova V. , Nayudu P.L. 
Published: April 2013

AbstractBackgroundChromosomal analyses were performed for marmosets from two colonies – Deutsches Primatenzentrum (DPZ) and Biomedical Primate Research Centre (BPRC). Chlorine‐based disinfectants are used in DPZ; no chemical disinfection is applied in BPRC.MethodsThe rates of chromosomal non‐disjunction, polyploidy and endoreduplication were investigated after G‐banding.ResultsFor DPZ monkeys, the mean rates of non‐disjunction were 7.6% for bone marrow and 11.3% for lymphocytes. The polyploidy level was 2.5% in bone marrow and 0.8% in blood. Frequency of endoreduplication in bone marrow and in leucocytes was 0.5% and 0.8%, respectively. For BPRC, the rate of non‐disjunction in leucocytes (1.3%) was significantly lower than that for DPZ; the polyploidy rate (0.2%) in blood was lower than that in DPZ; endoreduplication was not observed.ConclusionThe levels of chromosomal disorders are elevated for DPZ colony. We suggest that the increased rate of chromosomal disorders in DPZ marmosets can be related to the chemical disinfection of their environment.
Molecular analysis of the site for 2‐arachidonylglycerol (2‐AG) on the β2 subunit of GABAA receptors
Authors: Baur Roland , Kielar Marie , Richter Lars , Ernst Margot , Ecker Gerhard F. , Sigel Erwin 
Published: April 2013

Abstract2‐arachidonyl glycerol (2‐AG) allosterically potentiates GABAA receptors via a binding site located in transmembrane segment M4 of the β2 subunit. Two amino acid residues have been described that are essential for this effect. With the aim to further describe this potential drug target, we performed a cysteine scanning of the entire M4 and part of M3. All four residues in M4 affecting the potentiation here and the two already identified residues locate to the same side of the α‐helix. This side is exposed to M3, where further residues were identified. From the fact that the important residues span > 18 Å, we conclude that the hydrophobic tail of the bound 2‐AG molecule must be near linear and that the site mainly locates to the inner leaflet but stretches far into the membrane. The influence of the structure of the head group of the ligand molecule on the activity of the molecule was also investigated. We present a model of 2‐AG docked to the GABAA receptor.
Harnessing the power of yeast to unravel the molecular basis of neurodegeneration
Authors: Tenreiro Sandra , Munder Matthias C. , Alberti Simon , Outeiro Tiago F. 
Published: April 2013

AbstractSeveral neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), or prion diseases, are known for their intimate association with protein misfolding and aggregation. These disorders are characterized by the loss of specific neuronal populations in the brain and are highly associated with aging, suggesting a decline in proteostasis capacity may contribute to pathogenesis. Nevertheless, the precise molecular mechanisms that lead to the selective demise of neurons remain poorly understood. As a consequence, appropriate therapeutic approaches and effective treatments are largely lacking. The development of cellular and animal models that faithfully reproduce central aspects of neurodegeneration has been crucial for advancing our understanding of these diseases. Approaches involving the sequential use of different model systems, starting with simpler cellular models and ending with validation in more complex animal models, resulted in the discovery of promising therapeutic targets and small molecules with therapeutic potential. Within this framework, the simple and well‐characterized eukaryote Saccharomyces cerevisiae, also known as budding yeast, is being increasingly used to study the molecular basis of several neurodegenerative disorders. Yeast provides an unprecedented toolbox for the dissection of complex biological processes and pathways. Here, we summarize how yeast models are adding to our current understanding of several neurodegenerative disorders.
Calcium/calmodulin‐dependent serine protein kinase (CASK) is a new intracellular modulator of P2X3 receptors
Authors: Gnanasekaran Aswini , Sundukova Mayya , Hullugundi Swathi , Birsa Nicol , Bianchini Giorgio , Hsueh Yi‐Ping , Nistri Andrea , Fabbretti Elsa 
Published: April 2013

AbstractATP‐gated P2X3 receptors of sensory ganglion neurons are important transducers of painful stimuli and are modulated by extracellular algogenic substances, via changes in the receptor phosphorylation state. The present study investigated the role of calcium/calmodulin‐dependent serine protein kinase (CASK) in interacting and controlling P2X3 receptor expression and function in mouse trigeminal ganglia. Most ganglion neurons in situ or in culture co‐expressed P2X3 and CASK. CASK was immunoprecipitated with P2X3 receptors from trigeminal ganglia and from P2X3/CASK‐cotransfected human embryonic kidney (HEK) cells. Recombinant P2X3/CASK expression in HEK cells increased serine phosphorylation of P2X3 receptors, typically associated with receptor upregulation. CASK deletion mutants also enhanced P2X3 subunit expression. After silencing CASK, cell surface P2X3 receptor expression was decreased, which is consistent with depressed P2X3 currents. The reduction in P2X3 expression levels was reversed by the proteasomal inhibitor MG‐132. Moreover, neuronal CASK/P2X3 interaction was up‐regulated by nerve growth factor (NGF) signaling and down‐regulated by P2X3 agonist‐induced desensitization. These data suggest a novel interaction between CASK and P2X3 receptors with positive outcome for receptor stability and function. As CASK‐mediated control of P2X3 receptors was dependent on the receptor activation state, CASK represents an intracellular gateway to regulate purinergic nociceptive signaling.
Altered stress responsiveness and hypothalamic‐pituitary‐adrenal axis function in male rat offspring of socially isolated parents
Authors: Pisu Maria Giuseppina , Garau Anna , Olla Pierluigi , Biggio Francesca , Utzeri Cinzia , Dore Riccardo , Serra Mariangela 
Published: April 2013

AbstractSocial isolation in male rats at weaning results in reduced basal levels of the neuroactive steroid 3α,5α‐tetrahydroprogesterone (3α,5α‐TH PROG) in the brain and plasma as well as increased anxiety‐like behavior. We now show that socially isolated female rats also manifest a reduced basal cerebrocortical concentration of 3α,5α‐TH PROG as well as an anxiety‐like profile in the elevated plus‐maze and Vogel conflict tests compared with group‐housed controls. In contrast, despite the fact that they were raised under normal conditions, adult male offspring of male and female rats subjected to social isolation before mating exhibited an increased basal cerebrocortical level of 3α,5α‐TH PROG but no difference in emotional reactivity compared with the offspring of group‐housed parents. These animals also showed an increased basal activity of the hypothalamic‐pituitary‐adrenal axis as well as reduced abundance of corticotropin‐releasing factor in the hypothalamus and of corticotropin‐releasing factor receptor type 1 in the pituitary. Moreover, negative feedback regulation of hypothalamic‐pituitary‐adrenal axis activity by glucocorticoid was enhanced in association with up‐regulation of glucocorticoid receptor expression in the hippocampus. There was also attenuation of corticosterone release induced by foot‐shock stress in the offspring of socially isolated parents. The increase in the brain concentration of 3α,5α‐TH PROG induced by acute stress was also blunted in these animals. Our results thus show that a stressful experience before mating can influence neuroendocrine signaling in the next generation.
24(S)‐hydroxycholesterol is actively eliminated from neuronal cells by ABCA1
Authors: Matsuda Akihiro , Nagao Kohjiro , Matsuo Michinori , Kioka Noriyuki , Ueda Kazumitsu 
Published: April 2013

AbstractHigh cholesterol turnover catalyzed by cholesterol 24‐hydroxylase is essential for neural functions, especially learning. Because 24(S)‐hydroxycholesterol (24‐OHC), produced by 24‐hydroxylase, induces apoptosis of neuronal cells, it is vital to eliminate it rapidly from cells. Here, using differentiated SH‐SY5Y neuron‐like cells as a model, we examined whether 24‐OHC is actively eliminated via transporters induced by its accumulation. The expression of ABCA1 and ABCG1 was induced by 24‐OHC, as well as TO901317 and retinoic acid, which are ligands of the nuclear receptors liver X receptor/retinoid X receptor (LXR/RXR). When the expression of ABCA1 and ABCG1 was induced, 24‐OHC efflux was stimulated in the presence of high‐density lipoprotein (HDL), whereas apolipoprotein A‐I was not an efficient acceptor. The efflux was suppressed by the addition of siRNA against ABCA1, but not by ABCG1 siRNA. To confirm the role of each transporter, we analyzed human embryonic kidney 293 cells stably expressing human ABCA1 or ABCG1; we clearly observed 24‐OHC efflux in the presence of HDL, whereas efflux in the presence of apolipoprotein A‐I was marginal. Furthermore, the treatment of primary cerebral neurons with LXR/RXR ligands suppressed the toxicity of 24‐OHC. These results suggest that ABCA1 actively eliminates 24‐OHC in the presence of HDL as a lipid acceptor and protects neuronal cells.
Associations between EYA1 single‐nucleotide polymorphisms and non‐syndromic orofacial clefts in Western Han Chinese
Authors: Zeng Ni , Wu Jun , Zhu Wen‐Chao , Ma Li , Jia Zhong‐Lin , Shi Bing 
Published: April 2013

BackgroundNon‐syndromic orofacial clefts (NSOC) are the most common craniofacial birth defects and are considered as complex and multifactorial diseases involving the interplay of genetic predisposition and environmental exposures. Recent studies demonstrated that EYA1, a member of eye absent gene family, might contribute to the development of orofacial clefts. This study aimed to evaluate the association between EYA1 gene polymorphism and NSOC in western Chinese population.MethodTwo single‐nucleotide polymorphisms, rs13260349 and rs2380716, were investigated among 199 case–parent trios, and the linkage disequilibrium (LD) test, transmission disequilibrium test, family based association test, and haplotype analysis were performed.ResultsWeak evidence of LD was found between these markers (D' = 0.573, r2 = 0.218); allel C and genotype C/C at rs13260349 showed an overtransmission in CL/P; haplotype T‐T (rs13260349‐rs2380716) displayed an association with NSOC and CL/P.ConclusionsThe results showed evidence of weak association between the two SNPs of EYA1 (rs13260349 and rs2380716) and NSOC.