bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human iPSC derived disease model of MERTK-associated retinitis pigmentosa
Authors: Lukovic Dunja , Artero Castro Ana , Delgado Ana Belen Garcia , Bernal María de los Angeles Martín , Luna Pelaez Noelia , Díez Lloret Andrea , Perez Espejo Rocío , Kamenarova Kunka , Fernández Sánchez Laura , Cuenca Nicolás , Cortón Marta , Avila Fernandez Almudena , Sorkio Anni , Skottman Heli , Ayuso Carmen , Erceg Slaven , Bhattacharya Shomi S. 
Published: August 2015

AbstractRetinitis pigmentosa (RP) represents a genetically heterogeneous group of retinal dystrophies affecting mainly the rod photoreceptors and in some instances also the retinal pigment epithelium (RPE) cells of the retina. Clinical symptoms and disease progression leading to moderate to severe loss of vision are well established and despite significant progress in the identification of causative genes, the disease pathology remains unclear. Lack of this understanding has so far hindered development of effective therapies. Here we report successful generation of human induced pluripotent stem cells (iPSC) from skin fibroblasts of a patient harboring a novel Ser331Cysfs*5 mutation in the MERTK gene. The patient was diagnosed with an early onset and severe form of autosomal recessive RP (arRP). Upon differentiation of these iPSC towards RPE, patient-specific RPE cells exhibited defective phagocytosis, a characteristic phenotype of MERTK deficiency observed in human patients and animal models. Thus we have created a faithful cellular model of arRP incorporating the human genetic background which will allow us to investigate in detail the disease mechanism, explore screening of a variety of therapeutic compounds/reagents and design either combined cell and gene- based therapies or independent approaches.
Genetic data from algae sedimentary DNA reflect the influence of environment over geography
Authors: Stoof-Leichsenring Kathleen R. , Herzschuh Ulrike , Pestryakova Luidmila A. , Klemm Juliane , Epp Laura S. , Tiedemann Ralph 
Published: August 2015

AbstractGenetic investigations on eukaryotic plankton confirmed the existence of modern biogeographic patterns, but analyses of palaeoecological data exploring the temporal variability of these patterns have rarely been presented. Ancient sedimentary DNA proved suitable for investigations of past assemblage turnover in the course of environmental change, but genetic relatedness of the identified lineages has not yet been undertaken. Here, we investigate the relatedness of diatom lineages in Siberian lakes along environmental gradients (i.e. across treeline transects), over geographic distance and through time (i.e. the last 7000 years) using modern and ancient sedimentary DNA. Our results indicate that closely-related Staurosira lineages occur in similar environments and less-related lineages in dissimilar environments, in our case different vegetation and co-varying climatic and limnic variables across treeline transects. Thus our study reveals that environmental conditions rather than geographic distance is reflected by diatom-relatedness patterns in space and time. We tentatively speculate that the detected relatedness pattern in Staurosira across the treeline could be a result of adaptation to diverse environmental conditions across the arctic boreal treeline, however, a geographically-driven divergence and subsequent repopulation of ecologically different habitats might also be a potential explanation for the observed pattern.
Identification of key neoculin residues responsible for the binding and activation of the sweet taste receptor
Authors: Koizumi Taichi , Terada Tohru , Nakajima Ken-ichiro , Kojima Masaki , Koshiba Seizo , Matsumura Yoshitaka , Kaneda Kohei , Asakura Tomiko , Shimizu-Ibuka Akiko , Abe Keiko , Misaka Takumi 
Published: August 2015

AbstractNeoculin (NCL) is a heterodimeric protein isolated from the edible fruit ofCurculigo latifolia. It exerts a taste-modifying activity by converting sourness to sweetness. We previously demonstrated that NCL changes its action on the human sweet receptor hT1R2-hT1R3 from antagonism to agonism as the pH changes from neutral to acidic values and that the histidine residues of NCL molecule play critical roles in this pH-dependent functional change. Here, we comprehensively screened key amino acid residues of NCL using nuclear magnetic resonance (NMR) spectroscopy and alanine scanning mutagenesis. We found that the mutations of Arg48, Tyr65, Val72 and Phe94 of NCL basic subunit increased or decreased both the antagonist and agonist activities. The mutations had only a slight effect on the pH-dependent functional change. These residues should determine the affinity of NCL for the receptor regardless of pH. Their locations were separated from the histidine residues responsible for the pH-dependent functional change in the tertiary structure. From these results, we concluded that NCL interacts with hT1R2-hT1R3 through a pH-independent affinity interface including the four residues and a pH-dependent activation interface including the histidine residues. Thus, the receptor activation is induced by local structural changes in the pH-dependent interface.
Coagulation of β-conglycinin, glycinin and isoflavones induced by calcium chloride in soymilk
Authors: Hsiao Yu-Hsuan , Yu Chia-Jung , Li Wen-Tai , Hsieh Jung-Feng 
Published: August 2015

AbstractThe coagulation of β-conglycinin (7S), glycinin (11S) and isoflavones induced by calcium chloride was investigated. Approximately 92.6% of the soymilk proteins were coagulated into the soymilk pellet fraction (SPF) after the addition of 5 mM calcium chloride. SDS-PAGE and two-dimensional electrophoresis analysis indicated that most of the 7S (α’, α and β), 11S acidic (A1a, A1b, A2, A3 and A4) and 11S basic (B1a) proteins in the SSF were coagulated into the SPF after treatment with 5 mM calcium chloride. Isoflavones, including daidzein and genistein, were also coagulated into the SPF after the addition of 5 mM calcium chloride. The amounts of daidzein and genistein in the SSF decreased to 39.4 ± 1.6 and 11.8 ± 7.0%, respectively. HPLC analysis suggested that daidzein and genistein were bound with 7S and 11S proteins and then were coprecipitated into the SPF by 5 mM calcium chloride.
Pathways for protein transport to seed storage vacuoles
Authors: Jolliffe N.A. , Craddock C.P. , Frigerio L. 
Published: August 2015

Plant vacuoles have multiple functions: they can act both as digestive organelles and as receptacles for storage proteins. Different types of vacuoles can coexist in the same cell, which adds complexity to the process of targeting to these compartments. A fuller understanding of this process is of evident value when endeavouring to exploit the plant secretory pathway for heterologous protein production. Positive sorting signals are required in order to sort proteins to vacuoles, and these have been split into three groups: ctVSS [C-terminal VSS (vacuolar sorting signals)], ssVSS (sequence-specific VSS) and physical structure VSS. The current working model posits that soluble proteins are delivered from the Golgi apparatus to the lytic vacuoles in clathrin-coated vesicles by virtue of their ssVSS, or to the storage vacuole [PSV (protein-storage vacuole)] in dense vesicles in a manner dependent on ctVSS or physical structure VSS. Although targeting to LV appears to be receptor-mediated, no such receptor has been identified for the recruitment of proteins to the PSV. We have studied the vacuolar targeting of two castor bean (Ricinus communis L.) storage proteins, proricin and pro 2 S albumin, in their native endosperm and in the heterologous system of tobacco protoplasts. We have found that both these proteins contain bona fide ssVSS and bind to sorting receptors in vitro in a similarly sequence-specific manner. The apparent similarities to lytic VSS and possible implications with respect to the working model for transport to storage vacuoles are discussed.
Signalling role of adipose tissue: adipokines and inflammation in obesity
Authors: Trayhurn P. , Wood I.S. 
Published: August 2015

White adipose tissue (WAT) is a major endocrine and secretory organ, which releases a wide range of protein signals and factors termed adipokines. A number of adipokines, including leptin, adiponectin, tumour necrosis factor α, IL-1β (interleukin 1β), IL-6, monocyte chemotactic protein-1, macrophage migration inhibitory factor, nerve growth factor, vascular endothelial growth factor, plasminogen activator inhibitor 1 and haptoglobin, are linked to inflammation and the inflammatory response. Obesity is characterized by a state of chronic mild inflammation, with raised circulating levels of inflammatory markers and the expression and release of inflammation-related adipokines generally rises as adipose tissue expands (adiponectin, which has anti-inflammatory action is an exception). The elevated production of inflammation-related adipokines is increasingly considered to be important in the development of diseases linked to obesity, particularly Type II diabetes and the metabolic syndrome. WAT is involved in extensive cross-talk with other organs and multiple metabolic systems through the various adipokines.
Atypical L-type channels are down-regulated in hypoxia
Authors: Callinan L. , McCarthy T.V. , Maulet Y. , Mackrill J.J. 
Published: August 2015

One type of cellular response to hypoxia is an increase in cytosolic Ca2+. VDCCs (voltage-dependent calcium channels) open upon membrane depolarization allowing inward current of Ca2+ ions. Two of the so-called L-type VDCC α1 subunits, Cav1.2 and Cav1.3, are found in the brain. We sought to investigate the effect of chronic hypoxia or treatment with a hypoxia-mimicking agent DFX (desferrioxamine mesylate) on expression of L-type VDCC in the SH-SY5Y neuroblastoma cell line. Western blotting identified two atypical forms of the L-type channel with apparent molecular masses of approx. 100 and 150 kDa, compared with typical forms of approx. 200 kDa. Immunofluorescence microscopy shows the approx. 100 kDa protein located within the cell and on the cell surface, while the approx. 150 kDa protein is intracellular with punctate staining. Further analysis revealed that this approx. 150 kDa protein co-localizes with nuclear proteins but not with markers for other intracellular compartments. In addition, these proteins are both down-regulated in DFX-treated and hypoxic cells, suggesting that the mechanism of down-regulation is along the HIF (hypoxia-inducible factor) pathway. This atypical localization of the 150 kDa protein suggests that it might play a role in nuclear calcium signalling in health and disease.
Saccharomyces cerevisiae, a model to study sterol uptake and transport in eukaryotes
Authors: Reiner S. , Micolod D. , Schneiter R. 
Published: August 2015

The molecular mechanisms that govern intracellular transport of sterols in eukaryotic cells are only poorly understood. Saccharomyces cerevisiae is a facultative anaerobic organism that requires supplementation with unsaturated fatty acids and sterols to grow in the absence of oxygen, as the synthesis of these lipids requires molecular oxygen. The fact that yeast grows well under anaerobic conditions indicates that lipid uptake is rapid and efficient. To identify components in this lipid uptake and transport pathway, we screened the yeast mutant collection for genes that are essential under anaerobic conditions. Out of the approx. 4800 non-essential genes represented in the mutant collection, 37 were required for growth under anaerobic conditions. Uptake assays using radiolabelled cholesterol revealed that 16 of these genes are required for cholesterol uptake/transport and esterification. Further characterization of the precise role of these genes is likely to advance our understanding of this elusive pathway in yeast and may prove to be relevant to understand sterol homoeostasis in higher eukaryotic cells.
Characterization of AWAP IV, the C-terminal domain of the avian protein AWAK
Authors: Townes C.L. , Milona P. , Hall J. 
Published: August 2015

AWAP IV constitutes the C-terminal domain of the larger 81 kDa protein AWAK [Avian WAP (whey acidic protein) domain- and Kunitz domain-containing], which is predicted, through conserved domain database searching, to contain at least four WAP domains and one Kunitz domain. RT (reverse transcription)–PCR analyses revealed mRNA transcripts encoding AWAP IV in the small intestinal and kidney tissues of 5-day-old Salmonella-infected chicks. Time-kill antimicrobial assays using rAWAP IV (recombinant AWAP IV) cell lysate indicated antimicrobial activity against Gram-positive and Gram-negative bacteria including Salmonella, Streptococcus and Staphylococcus spp. In addition, permeabilization of the outer membrane of Salmonella, as shown by the NPN (N-phenyl-1-naphthylamine) fluorescent probe assay, supported the ability of rAWAP IV to disrupt prokaryotic membranes. WAP domains can function as inhibitors of serine protease activity, and the microbial serine proteases subtilisin and proteinase K were inhibited by rAWAP IV cell lysate. However, at comparable concentrations, no significant inhibition of the mammalian serine protease elastase was observed. The combined broad-spectrum antibacterial and anti-protease activities of AWAP IV suggest a novel role in the avian innate defence mechanisms operating against microbial infection.
Hot and crispy: CRISPR–Cas systems in the hyperthermophile Sulfolobus solfataricus
Authors: Zhang Jing , White Malcolm F. 
Published: August 2015

The CRISPR (clustered regularly interspaced short palindromic repeats) and Cas (CRISPR-associated) genes are widely spread in bacteria and archaea, representing an intracellular defence system against invading viruses and plasmids. In the system, fragments from foreign DNA are captured and integrated into the host genome at the CRISPR locus. The locus is transcribed and the resulting RNAs are processed by Cas6 into small crRNAs (CRISPR RNAs) that guide a variety of effector complexes to degrade the invading genetic elements. Many bacteria and archaea have one major type of effector complex. However, Sulfolobus solfataricus strain P2 has six CRISPR loci with two families of repeats, four cas6 genes and three different types of effector complex. These features make S. solfataricus an important model for studying CRISPR–Cas systems. In the present article, we review our current understanding of crRNA biogenesis and its effector complexes, subtype I-A and subtype III-B, in S. solfataricus. We also discuss the differences in terms of mechanisms between the subtype III-B systems in S. solfataricus and Pyrococcus furiosus.
The search for better epilepsy treatments: from slime mould to coconuts
Authors: Walker Matthew C. , Williams Robin S.B. 
Published: August 2015

Drug-resistant epilepsy has remained a problem since the inception of antiepileptic drug development, despite the large variety of antiepileptic drugs available today. Moreover, the mechanism-of-action of these drugs is often unknown. This is due to the widespread screening of compounds through animal models. We have taken a different approach to antiepileptic drug discovery and have identified a biochemical pathway in Dictyostelium discoideum (a ‘slime mould’) that may relate to the mechanism-of-action of valproate, one of the most commonly used and effective antiepileptic drugs. Through screening in this pathway, we have been able to identify a whole host of fatty acids and fatty acid derivatives with potential antiepileptic activity; this was then confirmed in in vitro and in vivo mammalian seizure models. Some of these compounds are more potent than valproate and potentially lack many of the major side effects of valproate (including birth defects and liver toxicity). In addition, one of the compounds that we have identified is a major constituent of the ketogenic diet, strongly arguing that it may be the fatty acids and not the ketogenesis that are mediating the effect of this diet.
Insight into a neuron's preferential susceptibility to oxidative stress
Authors: Bell Karen F.S. 
Published: August 2015

Neurons are more vulnerable to oxidative stress than astrocytes, the reasons for which have yet to be fully elucidated. Understanding the cellular and molecular mechanisms which contribute to this enhanced vulnerability is key to efforts aimed at ameliorating neuronal health and resilience to oxidative stress, particularly in the context of neurodegenerative disease, which is characterized by progressive dysfunction and loss of neurons specifically, and in which oxidative stress is considered a central aetiological contributor. Biological factors which may influence neuronal susceptibility to oxidative stress, in normal and neurodegenerative contexts, are reviewed in the present article, with a focus on properties intrinsic to the neuronal cell type and on properties related to neuronal reliance on surrounding astrocytes.
The collaborative roots of corruption
Authors: Weisel Ori , Shalvi Shaul 
Published: August 2015

SignificanceRecent financial scandals highlight the devastating consequences of corruption. While much is known about individual immoral behavior, little is known about the collaborative roots of curruption. In a novel experimental paradigm, people could adhere to one of two competing moral norms: collaborate vs. be honest. Whereas collaborative settings may boost honesty due to increased observability, accountability, and reluctance to force others to become accomplices, we show that collaboration, particularly on equal terms, is inductive to the emergence of corruption. When partners' profits are not aligned, or when individuals complete a comparable task alone, corruption levels drop. These findings reveal a dark side of collaboration, suggesting that human cooperative tendencies, and not merely greed, take part in shaping corruption.
Cryptic infection of a broad taxonomic and geographic diversity of tadpoles by Perkinsea protists
Authors: Chambouvet Aurélie , Gower David J. , Jirků Miloslav , Yabsley Michael J. , Davis Andrew K. , Leonard Guy , Maguire Finlay , Doherty-Bone Thomas M. , Bittencourt-Silva Gabriela Bueno , Wilkinson Mark , Richards Thomas A. 
Published: August 2015

Significance
Amphibians are among the most threatened animal groups. Population declines and extinctions have been linked, in part, to emerging infectious diseases. One such emerging disease has been attributed to Perkinsea-like protists causing mass mortality events in the United States. Using molecular methods, we evaluated the diversity of Perkinsea parasites in livers sampled from a wide taxonomic collection of tadpoles from six countries across three continents. We discovered a previously unidentified phylogenetically distinct infectious agent of tadpole livers present in a broad range of frogs from both tropical and temperate sites and across all sampled continents. These data demonstrate the high prevalence and global distribution of this infectious protist.
Interference effects of choice on confidence: Quantum characteristics of evidence accumulation
Authors: Kvam Peter D. , Pleskac Timothy J. , Yu Shuli , Busemeyer Jerome R. 
Published: August 2015

SignificanceMost cognitive and neural decision-making models—owing to their roots in classical probability theory—assume that decisions are read out of a definite state of accumulated evidence. This assumption contradicts the view held by many behavioral scientists that decisions construct rather than reveal beliefs and preferences. We present a quantum random walk model of decision-making that treats judgments and decisions as a constructive measurement process, and we report the results of an experiment showing that making a decision changes subsequent distributions of confidence relative to when no decision is made. This finding provides strong empirical support for a parameter-free prediction of the quantum model.
Dimerization of elongator protein 1 is essential for Elongator complex assembly
Authors: Xu Huisha , Lin Zhijie , Li Fengzhi , Diao Wentao , Dong Chunming , Zhou Hao , Xie Xingqiao , Wang Zheng , Shen Yuequan , Long Jiafu 
Published: August 2015

Significance
Elongator is a highly conserved multiprotein complex composed of six subunits elongator protein 1 (Elp1 to -6). Elongator has been associated with various cellular activities and has attracted clinical attention because of its role in certain neurodegenerative diseases. To understand the mechanism of Elongator assembly, we identified the highly conserved dimerization domain in both human and yeast Elp1 subunits and solved the crystal structures of the dimerization domains. This study is a mechanistic analysis of Elp1 dimerization, which plays an essential role in the integrity of functional Elongator and suggests that the pathological mechanisms underlying the onset and progression of Elp1 mutation-related diseases may result from impaired Elongator activities.
Mechanical coupling of the multiple structural elements of the large-conductance mechanosensitive channel during expansion
Authors: Li Jie , Guo Jianli , Ou Xiaomin , Zhang Mingfeng , Li Yuezhou , Liu Zhenfeng 
Published: August 2015

Significance
Mechanosensation underlies fundamental biological processes, including osmoregulation in microbes, touch and hearing in animals, and gravitropism and turgor pressure sensing in plants. The microbial large-conductance mechanosensitive channel (MscL) functions as a pressure-relief valve during hypoosmotic shock. MscL represents an ideal model system for investigating the molecular mechanism of the mechanical force transduction process. By solving and comparing the structures of an archaeal MscL in two different conformational states, we have revealed coordinated movements of the different domains of the MscL channel. Through this study, direct insights into the physical principle of the mechanical coupling mechanism, which coordinates the multiple structural elements of this highly sophisticated nanoscale valve, have been established.
Chemical fingerprints encode mother–offspring similarity, colony membership, relatedness, and genetic quality in fur seals
Authors: Stoffel Martin A. , Caspers Barbara A. , Forcada Jaume , Giannakara Athina , Baier Markus , Eberhart-Phillips Luke , Müller Caroline , Hoffman Joseph I. 
Published: August 2015

SignificanceUnderstanding olfactory communication in natural vertebrate populations requires knowledge of how genes and the environment influence highly complex individual chemical fingerprints. To understand how relevant information is chemically encoded and may feed into mother–offspring recognition, we therefore generated chemical and genetic data for Antarctic fur seal mother–pup pairs. We show that pups are chemically highly similar to their mothers, reflecting a combination of genetic and environmental influences. We also reveal associations between chemical fingerprints and both genetic quality and relatedness, the former correlating positively with substance diversity and the latter encoded mainly by a small subset of substances. Dissecting apart chemical fingerprints to reveal subsets of potential biological relevance has broad implications for understanding vertebrate chemical communication.