bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extra-skeletal manifestations in mice affected by Clcn7-dependent autosomal dominant osteopetrosis type 2 clinical and therapeutic implications
Authors: Maurizi Antonio , Capulli Mattia , Curle Annabel , Patel Rajvi , Ucci Argia , Côrtes Juliana Alves , Oxford Harriet , Lamandé Shireen R. , Bateman John F. , Rucci Nadia , Teti Anna 
Published: June 2019

AbstractAutosomal dominant osteopetrosis type 2 (ADO2) is a high-density brittle bone disease characterized by bone pain, multiple fractures and skeletal-related events, including nerve compression syndrome and hematological failure. We demonstrated that in mice carrying the heterozygousClcn7G213Rmutation, whose human mutant homologCLCN7G215Raffects patients, the clinical impacts of ADO2 extend beyond the skeleton, affecting several other organs. The hallmark of the extra-skeletal alterations is a consistent perivascular fibrosis, associated with high numbers of macrophages and lymphoid infiltrates. Fragmented clinical information in a small cohort of patients confirms extra-skeletal alterations consistent with a systemic disease, in line with the observation that theCLCN7gene is expressed in many organs. ADO2 mice also show anxiety and depression and their brains exhibit not only perivascular fibrosis but also β-amyloid accumulation and astrogliosis, suggesting the involvement of the nervous system in the pathogenesis of the ADO2 extra-skeletal alterations. Extra-skeletal organs share a similar cellular pathology, confirmed also in vitro in bone marrow mononuclear cells and osteoclasts, characterized by an impairment of the exit pathway of theClcn7protein product, ClC7, through the Golgi, with consequent reduced ClC7 expression in late endosomes and lysosomes, associated with high vesicular pH and accumulation of autophagosome markers. Finally, an experimental siRNA therapy, previously proven to counteract the bone phenotype, also improves the extra-skeletal alterations. These results could have important clinical implications, supporting the notion that a systematic evaluation of ADO2 patients for extra-skeletal symptoms could help improve their diagnosis, clinical management, and therapeutic options.
Selective elimination of cancer cells by the adenovirus E4orf4 protein in a Drosophila cancer model: a new paradigm for cancer therapy
Authors: Rosen Helit , Sharf Rakefet , Pechkovsky Antonina , Salzberg Adi , Kleinberger Tamar 
Published: June 2019

AbstractThe adenovirus (Ad) E4orf4 protein contributes to efficient progression of virus infection. When expressed alone E4orf4 induces p53- and caspase-independent cell-death, which is more effective in cancer cells than in normal cells in tissue culture. Cancer selectivity of E4orf4-induced cell-death may result from interference with various regulatory pathways that cancer cells are more dependent on, including DNA damage signaling and proliferation control. E4orf4 signaling is conserved in several organisms, including yeast, Drosophila, and mammalian cells, indicating that E4orf4-induced cell-death can be investigated in these model organisms. The Drosophila genetic model system has contributed significantly to the study of cancer and to identification of novel cancer therapeutics. Here, we used the fly model to investigate the ability of E4orf4 to eliminate cancer tissues in a whole organism with minimal damage to normal tissues. We show that E4orf4 dramatically inhibited tumorigenesis and rescued survival of flies carrying a variety of tumors, including highly aggressive and metastatic tumors in the fly brain and eye discs. Moreover, E4orf4 rescued the morphology of adult eyes containing scrib− cancer clones even when expressed at a much later stage than scrib elimination. The E4orf4 partner protein phosphatase 2A (PP2A) was required for inhibition of tumorigenesis by E4orf4 in the system described here, whereas another E4orf4 partner, Src kinase, provided only minimal contribution to this process. Our results suggest that E4orf4 is an effective anticancer agent and reveal a promising potential for E4orf4-based cancer treatments.
Lobular architecture of human adipose tissue defines the niche and fate of progenitor cells
Authors: Estève D. , Boulet N. , Belles C. , Zakaroff-Girard A. , Decaunes P. , Briot A. , Veeranagouda Y. , Didier M. , Remaury A. , Guillemot J. C. , Ledoux S. , Dani C. , Bouloumié A. , Galitzky J. 
Published: June 2019

AbstractHuman adipose tissue (hAT) is constituted of structural units termed lobules, the organization of which remains to be defined. Here we report that lobules are composed of two extracellular matrix compartments, i.e., septa and stroma, delineating niches of CD45−/CD34+/CD31− progenitor subsets characterized by MSCA1 (ALPL) and CD271 (NGFR) expression. MSCA1+ adipogenic subset is enriched in stroma while septa contains mainly MSCA1−/CD271− and MSCA1−/CD271high progenitors. CD271 marks myofibroblast precursors and NGF ligand activation is a molecular relay of TGFβ-induced myofibroblast conversion. In human subcutaneous (SC) and visceral (VS) AT, the progenitor subset repartition is different, modulated by obesity and in favor of adipocyte and myofibroblast fate, respectively. Lobules exhibit depot-specific architecture with marked fibrous septa containing mesothelial-like progenitor cells in VSAT. Thus, the human AT lobule organization in specific progenitor subset domains defines the fat depot intrinsic capacity to remodel and may contribute to obesity-associated cardiometabolic risks.
High gas barrier coating using non-toxic nanosheet dispersions for flexible food packaging film
Authors: Yu Jingfang , Ruengkajorn Kanittika , Crivoi Dana-Georgiana , Chen Chunping , Buffet Jean-Charles , O’Hare Dermot 
Published: June 2019

AbstractOne of the major challenges in the circular economy relating to food packaging is the elimination of metallised film which is currently the industry standard approach to achieve the necessary gas barrier performance. Here, we report the synthesis of high aspect ratio 2D non-toxic layered double hydroxide (LDH) nanosheet dispersions using a non-toxic exfoliation method in aqueous amino acid solution. High O2 and water vapour barrier coating films can be prepared using food safe liquid dispersions through a bar coating process. The oxygen transmission rate (OTR) of 12 μm PET coated film can be reduced from 133.5 cc·m−2·day−1 to below the instrument detection limit (<0.005 cc·m−2·day−1). The water vapour transmission rate (WVTR) of the PET film can be reduced from 8.99 g·m−2·day−1 to 0.04 g·m−2·day−1 after coating. Most importantly, these coated films are also transparent and mechanically robust, making them suitable for flexible food packing while also offering new recycling opportunities.
Translatome analysis reveals altered serine and glycine metabolism in T-cell acute lymphoblastic leukemia cells
Authors: Kampen Kim R. , Fancello Laura , Girardi Tiziana , Rinaldi Gianmarco , Planque Mélanie , Sulima Sergey O. , Loayza-Puch Fabricio , Verbelen Benno , Vereecke Stijn , Verbeeck Jelle , Op de Beeck Joyce , Royaert Jonathan , Vermeersch Pieter , Cassiman David , Cools Jan , Agami Reuven , Fiers Mark , Fendt Sarah-Maria , De Keersmaecker Kim 
Published: June 2019

AbstractSomatic ribosomal protein mutations have recently been described in cancer, yet their impact on cellular transcription and translation remains poorly understood. Here, we integrate mRNA sequencing, ribosome footprinting, polysomal RNA sequencing and mass spectrometry datasets from a mouse lymphoid cell model to characterize the T-cell acute lymphoblastic leukemia (T-ALL) associated ribosomal RPL10 R98S mutation. Surprisingly, RPL10 R98S induces changes in protein levels primarily through transcriptional rather than translation efficiency changes. Phosphoserine phosphatase (PSPH), encoding a key serine biosynthesis enzyme, was the only gene with elevated transcription and translation leading to protein overexpression. PSPH upregulation is a general phenomenon in T-ALL patient samples, associated with elevated serine and glycine levels in xenograft mice. Reduction of PSPH expression suppresses proliferation of T-ALL cell lines and their capacity to expand in mice. We identify ribosomal mutation driven induction of serine biosynthesis and provide evidence supporting dependence of T-ALL cells on PSPH.
Stepwise on-surface dissymmetric reaction to construct binodal organometallic network
Authors: Liu Jing , Chen Qiwei , Cai Kang , Li Jie , Li Yaru , Yang Xiao , Zhang Yajie , Wang Yongfeng , Tang Hao , Zhao Dahui , Wu Kai 
Published: June 2019

AbstractDissymmetric reactions, which enable differentiated functionalization of equivalent sites within one molecule, have many potential applications in synthetic chemistry and materials science, but they are very challenging to achieve. Here, the dissymmetric reaction of 1,4-dibromo-2,5-diethynylbenzene (2Br-DEB) on Ag(111) is realized by using a stepwise activation strategy, leading to an ordered two-dimensional organometallic network containing both alkynyl–silver–alkynyl and alkynyl–silver–phenyl nodes. Scanning tunneling microscopy and density functional theory calculations are employed to explore the stepwise conversion of 2Br-DEB, which starts from the H-passivation of one Br-substituted site at 300 K in accompaniment with an intermolecular reaction to form one-dimensional organometallic chains containing alkynyl–silver–alkynyl nodes. Afterwards, the other equivalent Br-substituted site undergoes metalation reaction at 320–450 K, resulting in transformation of the chains into the binodal networks. These findings exemplify the achievement of the dissymmetric reaction and its practical application for controlled fabrications of complicated yet ordered nanostructures on a surface.
Learning of distant state predictions by the orbitofrontal cortex in humans
Authors: Elliott Wimmer G. , Büchel Christian 
Published: June 2019

AbstractRepresentations of our future environment are essential for planning and decision making. Previous research in humans has demonstrated that the hippocampus is a critical region for forming and retrieving associations, while the medial orbitofrontal cortex (OFC) is an important region for representing information about recent states. However, it is not clear how the brain acquires predictive representations during goal-directed learning. Here, we show using fMRI that while participants learned to find rewards in multiple different Y-maze environments, hippocampal activity was highest during initial exposure and then decayed across the remaining repetitions of each maze, consistent with a role in rapid encoding. Importantly, multivariate patterns in the OFC-VPFC came to represent predictive information about upcoming states approximately 30 s in the future. Our findings provide a mechanism by which the brain can build models of the world that span long-timescales to make predictions.
Facial recognition from DNA using face-to-DNA classifiers
Authors: Sero Dzemila , Zaidi Arslan , Li Jiarui , White Julie D. , Zarzar Tomás B. González , Marazita Mary L. , Weinberg Seth M. , Suetens Paul , Vandermeulen Dirk , Wagner Jennifer K. , Shriver Mark D. , Claes Peter 
Published: June 2019

AbstractFacial recognition from DNA refers to the identification or verification of unidentified biological material against facial images with known identity. One approach to establish the identity of unidentified biological material is to predict the face from DNA, and subsequently to match against facial images. However, DNA phenotyping of the human face remains challenging. Here, another proof of concept to biometric authentication is established by using multiple face-to-DNA classifiers, each classifying given faces by a DNA-encoded aspect (sex, genomic background, individual genetic loci), or by a DNA-inferred aspect (BMI, age). Face-to-DNA classifiers on distinct DNA aspects are fused into one matching score for any given face against DNA. In a globally diverse, and subsequently in a homogeneous cohort, we demonstrate preliminary, but substantial true (83%, 80%) over false (17%, 20%) matching in verification mode. Consequences of future efforts include forensic applications, necessitating careful consideration of ethical and legal implications for privacy in genomic databases.
Experimental demonstration of quantum finite automaton
Authors: Tian Yuling , Feng Tianfeng , Luo Maolin , Zheng Shenggen , Zhou Xiaoqi 
Published: June 2019

AbstractIn quantum information science, a major task is to find the quantum models that can outperform their classical counterparts. Automaton is a fundamental computing model that has wide applications in many fields. It has been shown that the quantum version of automaton can solve certain problem using a much smaller state space compared to the classical automaton. Here we report an experimental demonstration of an optical quantum automaton, which is used to solve the promise problems of determining whether the length of an input string can be divided by a prime number P with no remainder or with a remainder of R. Our quantum automaton can solve such problem using a state space with only three orthonormal states, whereas the classical automaton needs no less than P states. Our results demonstrate the quantum benefits of a quantum automaton over its classical counterpart and paves the way for implementing quantum automaton for more complicated and practical applications.
Scenedesnus rotundus isolated from the petroleum effluent employs alternate mechanisms of tolerance to elevated levels of Cadmium and Zinc
Authors: Shivaji Subhashini , V. L. Dronamaraju Sarada 
Published: June 2019

AbstractScenedesmus rotundus was isolated from metal contaminated petroleum industry effluent and its tolerance to Cadmium and Zinc was tested using different concentrations of CdCl2 and ZnCl2 ranging from 0.001 mM to 1.0 mM of Cd and 0.03 mM to 1.21 mM of Zn amended in Bolds Basal medium. The changes in cell count recorded at regular intervals upto a period of 24 days revealed a concentration dependent inhibition in growth. Concentration of the metal, at which 50% of the cells are live and metabolically active referred to as EC50 was calculated as 0.04 mM for Cd and 0.2 mM for Zn. Further, the effect of EC50 of the metals on the protein content, uptake of metals at varying pH, oxidative stress markers including lipid peroxidation, protein oxidation andnd oxygen uptake, levels of enzymatic antioxidants such as catalase and superoxide dismutase and non-enzymatic antioxidants namely, GSH and PC4 were determined. Though a direct correlation could not be drawn between pH and metal uptake, the compartmentalization of the metal during the lag phase and exponential phase was evident, most of the metal was present in extracellular fractions in the former, while in the later it was internalized. Our study shows a clear correlation between toxicity of Cd and the ability of the algae to synthesize PC4 from GSH and chelate it leading to detoxification, while Zn treatment led to an increase in the activity of catalase and superoxide dismutase and replete GSH pools. Further the changes in the cell wall structure at EC50 of Cd and Zn were studied. This is the first report on effect of heavy metals on the structural modifications of the cell wall of Scenedesmus in general and Scenedesmus rotundus in particular, indicating appearance of granules on the entire cell surface in both Cd and Zn treatments, with the degree of granulation increasing in the order of pH 12 > 10 > 8 in Cd treatment. Further structures of higher order resembling minute wheels are observed in Cd treated cells are also reported.
Cadherin CsCad plays differential functional roles in Cry1Ab and Cry1C intoxication in Chilo suppressalis
Authors: Du Lixiao , Chen Geng , Han Lanzhi , Peng Yufa 
Published: June 2019

AbstractTransgenic rice lines expressing Bacillus thuringiensis (Bt) toxins have been successfully developed for the control of Chilo suppressalis. However, the evolution of insect resistance is a major threat to Bt rice durability. Bt toxins function by binding specific receptors in the midgut of target insects; specifically, cadherin proteins have been identified as Cry toxin receptors in diverse lepidopteran species. Here, we report the functional roles of cadherin CsCad in the midgut of C. suppressalis in Cry1Ab and Cry1C toxicity. We expressed a recombinant truncated CsCad peptide (CsCad-CR11-MPED) in Escherichia coli that included the eleventh cadherin repeat and MPED region. Based on ligand blotting and ELISA binding assays, the CsCad-CR11-MPED peptide specifically bound Cry1Ab with high affinity but weakly bound Cry1C. The CsCad-CR11-MPED peptide significantly enhanced the susceptibility of C. suppressalis larvae to Cry1Ab but not Cry1C. Furthermore, the knockdown of endogenous CsCad with Stealth siRNA reduced C. suppressalis larval susceptibility to Cry1Ab but not Cry1C, suggesting that CsCad plays differential functional roles in Cry1Ab and Cry1C intoxication in C. suppressalis. This information directly enhances our understanding of the potential resistance mechanisms of C. suppressalis against Bt toxins and may assist in the development of effective strategies for delaying insect resistance.
Pathological changes in the lymphatic system of patients with secondary upper limb lymphoedema
Authors: Mikami Taro , Koyama Asumi , Hashimoto Koukichi , Maegawa Jiro , Yabuki Yuichiro , Kagimoto Shintaro , Kitayama Shinya , Kaneta Tomohiro , Yasumura Kazunori , Matsubara Shinobu , Iwai Toshinori 
Published: June 2019

AbstractSecondary upper limb lymphoedema is usually caused by lymphatic system dysfunction. Diagnosis is primarily based on clinical features. However, there are no distinct diagnostic criteria for lymphoedema. Although conventional lymphoscintigraphy is a useful technique to diagnose the severity of lymphoedema, the resultant data are two-dimensional. In this study, we examined the pathology of lymphoedema using single photon emission computed tomography-computed tomography lymphoscintigraphy (SPECT-CT LSG), a new technique that provides 3-dimensional information on lymph flow. We observed lymph flow pathways in the subcutaneous and muscle layers of the upper limbs. A significant positive correlation was found between the dermal back flow (DBF) type and the visualization of lymph nodes around the clavicle (p = 0.000266), the type of lymph flow pathways and the visualization of lymph nodes around the clavicle (p = 0.00963), and the DBF type and the lymph flow pathway (p = 0.00766). As the severity of lymphoedema increased, the DBF appeared more distally in the upper limb and the flow into the lymph nodes around the clavicle decreased, whereas the lymph flow pathways in the muscle layer became dominant. These findings demonstrate the features of lymphoedema pathology and the functional anatomy and physiology of the lymphatic system without the need for cadaver dissection.
Ganglioside GQ1b ameliorates cognitive impairments in an Alzheimer’s disease mouse model, and causes reduction of amyloid precursor protein
Authors: Shin Min-Kyoo , Choi Min-Suk , Chae Hyang-Ji , Kim Ji-Won , Kim Hong-Gi , Kim Kil-Lyong 
Published: June 2019

AbstractBrain-derived neurotrophic factor (BDNF) plays crucial roles in memory impairments including Alzheimer’s disease (AD). Previous studies have reported that tetrasialoganglioside GQ1b is involved in long-term potentiation and cognitive functions as well as BDNF expression. However, in vitro and in vivo functions of GQ1b against AD has not investigated yet. Consequently, treatment of oligomeric Aβ followed by GQ1b significantly restores Aβ1–42-induced cell death through BDNF up-regulation in primary cortical neurons. Bilateral infusion of GQ1b into the hippocampus ameliorates cognitive deficits in the triple-transgenic AD mouse model (3xTg-AD). GQ1b-infused 3xTg-AD mice had substantially increased BDNF levels compared with artificial cerebrospinal fluid (aCSF)-treated 3xTg-AD mice. Interestingly, we also found that GQ1b administration into hippocampus of 3xTg-AD mice reduces Aβ plaque deposition and tau phosphorylation, which correlate with APP protein reduction and phospho-GSK3β level increase, respectively. These findings demonstrate that the tetrasialoganglioside GQ1b may contribute to a potential strategy of AD treatment.
Non-neutral evolution of H3.3-encoding genes occurs without alterations in protein sequence
Authors: Muhire Brejnev M. , Booker Matthew A. , Tolstorukov Michael Y. 
Published: June 2019

AbstractHistone H3.3 is a developmentally essential variant encoded by two independent genes in human (H3F3A and H3F3B). While this two-gene arrangement is evolutionarily conserved, its origins and function remain unknown. Phylogenetics, synteny and gene structure analyses of H3.3 genes from 32 metazoan genomes indicate independent evolutionary paths for H3F3A and H3F3B. While H3F3B bears similarities with H3.3 genes in distant organisms and with canonical H3 genes, H3F3A is sarcopterygian-specific and evolves under strong purifying selection. Additionally, H3F3B codon-usage preferences resemble those of broadly expressed genes and ‘cell differentiation-induced’ genes, while codon-usage of H3F3A resembles that of ‘cell proliferation-induced’ genes. We infer that H3F3B is more similar to the ancestral H3.3 gene and likely evolutionarily adapted for a broad expression pattern in diverse cellular programs, while H3F3A adapted for a subset of gene expression programs. Thus, the arrangement of two independent H3.3 genes facilitates fine-tuning of H3.3 expression across cellular programs.
Designing contrasts for rapid, simultaneous parameter quantification and flow visualization with quantitative transient-state imaging
Authors: Gómez Pedro A. , Molina-Romero Miguel , Buonincontri Guido , Menzel Marion I. , Menze Bjoern H. 
Published: June 2019

AbstractMagnetic resonance imaging (MRI) has evolved into an outstandingly versatile diagnostic modality, as it has the ability to non-invasively produce detailed information on a tissue’s structure and function. Complementary data is normally obtained in separate measurements, either as contrast-weighted images, which are fast and simple to acquire, or as quantitative parametric maps, which offer an absolute quantification of underlying biophysical effects, such as relaxation times or flow. Here, we demonstrate how to acquire and reconstruct data in a transient-state with a dual purpose: 1 – to generate contrast-weighted images that can be adjusted to emphasise clinically relevant image biomarkers; exemplified with signal modulation according to flow to obtain angiography information, and 2 – to simultaneously infer multiple quantitative parameters with a single, highly accelerated acquisition. This is achieved by introducing three novel elements: a model that accounts for flowing blood, a method for sequence design using smooth flip angle excitation patterns that incorporates both parameter encoding and signal contrast, and the reconstruction of temporally resolved contrast-weighted images. From these images we simultaneously obtain angiography projections and multiple quantitative maps. By doing so, we increase the amount of clinically relevant data without adding measurement time, creating new dimensions for biomarker exploration and adding value to MR examinations for patients and clinicians alike.