bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual
Authors: Merceron Christophe , Ranganathan Kavitha , Wang Elizabeth , Tata Zachary , Makkapati Shreya , Khan Mohd Parvez , Mangiavini Laura , Yao Angela Qing , Castellini Laura , Levi Benjamin , Giaccia Amato J. , Schipani Ernestina 
Published: February 2019

AbstractOsteoblasts, which are the bone-forming cells, operate in a hypoxic environment. The transcription factors hypoxia-inducible factor-1α (HIF1) and HIF2 are key mediators of the cellular response to hypoxia. Both are expressed in osteoblasts. HIF1 is known to be a positive regulator of bone formation. Conversely, the role of HIF2 in the control osteoblast biology is still poorly understood. In this study, we used mouse genetics to demonstrate that HIF2 is an inhibitor of osteoblastogenesis and bone mass accrual. Moreover, we provided evidence that HIF2 impairs osteoblast differentiation at least in part, by upregulating the transcription factor Sox9. Our findings constitute a paradigm shift, as activation of the hypoxia-signaling pathway has traditionally been associated with increased bone formation through HIF1. Inhibiting HIF2 could thus represent a therapeutic approach for the treatment of the low bone mass observed in chronic diseases, osteoporosis, or aging.
Promoting electrocatalytic CO2 reduction to formate via sulfur-boosting water activation on indium surfaces
Authors: Ma Wenchao , Xie Shunji , Zhang Xia-Guang , Sun Fanfei , Kang Jincan , Jiang Zheng , Zhang Qinghong , Wu De-Yin , Wang Ye 
Published: February 2019

AbstractElectrocatalytic reduction of CO2 to fuels and chemicals is one of the most attractive routes for CO2 utilization. Current catalysts suffer from low faradaic efficiency of a CO2-reduction product at high current density (or reaction rate). Here, we report that a sulfur-doped indium catalyst exhibits high faradaic efficiency of formate (>85%) in a broad range of current density (25–100 mA cm−2) for electrocatalytic CO2 reduction in aqueous media. The formation rate of formate reaches 1449 μmol h−1 cm−2 with 93% faradaic efficiency, the highest value reported to date. Our studies suggest that sulfur accelerates CO2 reduction by a unique mechanism. Sulfur enhances the activation of water, forming hydrogen species that can readily react with CO2 to produce formate. The promoting effect of chalcogen modifiers can be extended to other metal catalysts. This work offers a simple and useful strategy for designing both active and selective electrocatalysts for CO2 reduction.
A platform for glycoengineering a polyvalent pneumococcal bioconjugate vaccine using E. coli as a host
Authors: Harding Christian M. , Nasr Mohamed A. , Scott Nichollas E. , Goyette-Desjardins Guillaume , Nothaft Harald , Mayer Anne E. , Chavez Sthefany M. , Huynh Jeremy P. , Kinsella Rachel L. , Szymanski Christine M. , Stallings Christina L. , Segura Mariela , Feldman Mario F. 
Published: February 2019

AbstractChemical synthesis of conjugate vaccines, consisting of a polysaccharide linked to a protein, can be technically challenging, and in vivo bacterial conjugations (bioconjugations) have emerged as manufacturing alternatives. Bioconjugation relies upon an oligosaccharyltransferase to attach polysaccharides to proteins, but currently employed enzymes are not suitable for the generation of conjugate vaccines when the polysaccharides contain glucose at the reducing end, which is the case for ~75% of Streptococcus pneumoniae capsules. Here, we use an O-linking oligosaccharyltransferase to generate a polyvalent pneumococcal bioconjugate vaccine with polysaccharides containing glucose at their reducing end. In addition, we show that different vaccine carrier proteins can be glycosylated using this system. Pneumococcal bioconjugates are immunogenic, protective and rapidly produced within E. coli using recombinant techniques. These proof-of-principle experiments establish a platform to overcome limitations of other conjugating enzymes enabling the development of bioconjugate vaccines for many important human and animal pathogens.
Combined surgery and chondrocyte cell-sheet transplantation improves clinical and structural outcomes in knee osteoarthritis
Authors: Sato Masato , Yamato Masayuki , Mitani Genya , Takagaki Tomonori , Hamahashi Kosuke , Nakamura Yoshihiko , Ishihara Miya , Matoba Ryo , Kobayashi Hiroyuki , Okano Teruo , Mochida Joji , Watanabe Masahiko 
Published: February 2019

AbstractCurrent cartilage regenerative therapies are not fully effective in treating osteoarthritis of the knee (OAK). We have developed chondrocyte sheets for autologous transplantation and tested these in in vitro and in vivo preclinical studies, and have reported that the transplantation of chondrocyte sheets promoted hyaline cartilage repair in rat, rabbit, and minipig models. However, autologous transplantation of chondrocyte sheets has yet to be reported in humans. Here, we report our combination therapy in which conventional surgical treatment for OAK, is followed by autologous chondrocyte sheet transplantation for cartilage repair. Eight patients with OAK and cartilage defects categorized arthroscopically as Outerbridge grade III or IV receive the therapy. Patients are thoroughly assessed by preoperative and postoperative X-rays, magnetic resonance imaging (MRI), arthroscopy, Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm Knee Score (LKS), and a laser-induced photoacoustic method to assess cartilage viscoelasticity. Arthroscopic biopsies of all patients are performed 12 months after transplantation for histological evaluation. The properties of the chondrocyte sheets are evaluated using gene expression analysis to investigate the ability to predict the clinical and structural outcomes of the therapy. For this small initial longitudinal series, combination therapy is effective, as assessed by MRI, arthroscopy, viscoelasticity, histology, and the clinical outcomes of KOOS and LKS. Gene marker sets identified in autologous chondrocyte sheets may be predictive of the overall KOOS, LKS, and histological scores after therapy. These predictive gene sets may be potential alternative markers for evaluating OAK treatment.
Cilioretinal Arteries and Cilioretinal Veins in Eyes with Pathologic Myopia
Authors: Watanabe Takashi , Kasahara Kaori , Futagami Soh , Fang Yuxin , Du Ran , Moriyama Muka , Uramoto Kengo , Yokoi Tae , Onishi Yuka , Yoshida Takeshi , Kamoi Koju , Jonas Jost B. , Ohno-Matsui Kyoko 
Published: February 2019

AbstractWe investigated the clinical characteristics of cilioretinal arteries (CAs) and cilioretinal veins (CVs) in eyes with pathologic myopia. Ninety-five eyes with pathologic myopia and CAs were studied. The retrobulbar vessels from which the CAs originated were identified by indocyanine green angiography (ICGA). The results showed that 114 CAs were identified in the 95 eyes. ICGA showed that 60% of the CAs branched directly off the short posterior ciliary arteries (SPCAs) and 40% originated from the Zinn-Haller arterial circle (ZHAC). The SPCA-derived CAs tended to be located superiorly and served a large retinal area whereas the ZHAC-associated CAs tended to be located temporally and served mainly the macular area. In 15% of the 95 eyes, the CVs were observed to run parallel to the CAs. The CVs exited the eye at the same point where the CAs entered the eye. This study showed that CAs in eyes with pathologic myopia can be divided into those that are SPCA-derived and tend to emerge in the superior optic disc sector, and those that are ZHAC-associated and usually emerge temporally. An elongating peripapillary scleral flange in eyes with progressive axial myopia may lead to a change of chorioretinal vascular system.
Exploring the suitability of RanBP2-type Zinc Fingers for RNA-binding protein design
Authors: De Franco Simona , Vandenameele Julie , Brans Alain , Verlaine Olivier , Bendak Katerina , Damblon Christian , Matagne André , Segal David J. , Galleni Moreno , Mackay Joel P. , Vandevenne Marylène 
Published: February 2019

AbstractTranscriptomes consist of several classes of RNA that have wide-ranging but often poorly described functions and the deregulation of which leads to numerous diseases. Engineering of functionalized RNA-binding proteins (RBPs) could therefore have many applications. Our previous studies suggested that the RanBP2-type Zinc Finger (ZF) domain is a suitable scaffold to investigate the design of single-stranded RBPs. In the present work, we have analyzed the natural sequence specificity of various members of the RanBP2-type ZF family and characterized the interaction with their target RNA. Surprisingly, our data showed that natural RanBP2-type ZFs with different RNA-binding residues exhibit a similar sequence specificity and therefore no simple recognition code can be established. Despite this finding, different discriminative abilities were observed within the family. In addition, in order to target a long RNA sequence and therefore gain in specificity, we generated a 6-ZF array by combining ZFs from the RanBP2-type family but also from different families, in an effort to achieve a wider target sequence repertoire. We showed that this chimeric protein recognizes its target sequence (20 nucleotides), both in vitro and in living cells. Altogether, our results indicate that the use of ZFs in RBP design remains attractive even though engineering of specificity changes is challenging.
Chromosome transmission in BC4 progenies of intergeneric hybrids between Saccharum spp. and Erianthus arundinaceus (Retz.) Jeswiet
Authors: Yang Shan , Zeng Kai , Chen Ke , Wu Jiayun , Wang Qinnan , Li Xueting , Deng Zuhu , Huang Yongji , Huang Fei , Chen Rukai , Zhang Muqing 
Published: February 2019

AbstractIntergeneric hybrids between Saccharum spp. and Erianthus arundinaceus and clones derived from these hybrids and backcrosses to Saccharum spp. were used to study the transmission of E. arundinaceus chromosomes by genomic in situ hybridization (GISH). True hybrid progenies were precisely identified using PCR with a primer pair, AGRP52/53. The results showed that AGRP52/53 was an E. arundinaceus-specific primer pair and could be used as molecular marker to assist breeding. EaHN92, a 364 bp E. arundinaceus-specific tandem repeat satellite DNA sequence, was cloned from the E. arundinaceus clone HN92–105 with AGRP52/53, and was localized on sub-telomeric regions of all E. arundinaceus chromosomes. YCE06–61, a BC3 progeny, had 7 E. arundinaceus chromosomes and its progenies had approximately 1–6 E. arundinaceus chromosomes. The number of E. arundinaceus chromosomes in true hybrids appeared as Gaussian distribution in 3 cross combinations. In addition, GISH detected intergeneric chromosome translocation in a few progenies. Hence, screening clones containing approximately 1–2 E. arundinaceus chromosomes without translocation could be used for sorting and sequencing E. arundinaceus chromosomes. This study provides a method for breeders to select true hybrid progenies between Saccharum spp. and E. arundinaceus, which will accelerate this intergeneric hybridization breeding.
A climate-driven and field data-assimilated population dynamics model of sand flies
Authors: Erguler Kamil , Pontiki Irene , Zittis George , Proestos Yiannis , Christodoulou Vasiliki , Tsirigotakis Nikolaos , Antoniou Maria , Kasap Ozge Erisoz , Alten Bulent , Lelieveld Jos 
Published: February 2019

AbstractSand flies are responsible for the transmission of leishmaniasis, a neglected tropical disease claiming more than 50,000 lives annually. Leishmaniasis is an emerging health risk in tropical and Mediterranean countries as well as temperate regions in North America and Europe. There is an increasing demand for predicting population dynamics and spreading of sand flies to support management and control, yet phenotypic diversity and complex environmental dependence hamper model development. Here, we present the principles for developing predictive species-specific population dynamics models for important disease vectors. Based on these principles, we developed a sand fly population dynamics model with a generic structure where model parameters are inferred using a surveillance dataset collected from Greece and Cyprus. The model incorporates distinct life stages and explicit dependence on a carefully selected set of environmental variables. The model successfully replicates the observations and demonstrates high predictive capacity on the validation dataset from Turkey. The surveillance datasets inform about biological processes, even in the absence of laboratory experiments. Our findings suggest that the methodology can be applied to other vector species to predict abundance, control dispersion, and help to manage the global burden of vector-borne diseases.
Covariance statistics and network analysis of brain PET imaging studies
Authors: Veronese Mattia , Moro Lucia , Arcolin Marco , Dipasquale Ottavia , Rizzo Gaia , Expert Paul , Khan Wasim , Fisher Patrick M. , Svarer Claus , Bertoldo Alessandra , Howes Oliver , Turkheimer Federico E. 
Published: February 2019

AbstractThe analysis of structural and functional neuroimaging data using graph theory has increasingly become a popular approach for visualising and understanding anatomical and functional relationships between different cerebral areas. In this work we applied a network-based approach for brain PET studies using population-based covariance matrices, with the aim to explore topological tracer kinetic differences in cross-sectional investigations. Simulations, test-retest studies and applications to cross-sectional datasets from three different tracers ([18F]FDG, [18F]FDOPA and [11C]SB217045) and more than 400 PET scans were investigated to assess the applicability of the methodology in healthy controls and patients. A validation of statistics, including the assessment of false positive differences in parametric versus permutation testing, was also performed. Results showed good reproducibility and general applicability of the method within the range of experimental settings typical of PET neuroimaging studies, with permutation being the method of choice for the statistical analysis. The use of graph theory for the quantification of [18F]FDG brain PET covariance, including the definition of an entropy metric, proved to be particularly relevant for Alzheimer’s disease, showing an association with the progression of the pathology. This study shows that covariance statistics can be applied to PET neuroimaging data to investigate the topological characteristics of the tracer kinetics and its related targets, although sensitivity to experimental variables, group inhomogeneities and image resolution need to be considered when the method is applied to cross-sectional studies.
Laser-induced breakdown spectroscopy (LIBS) as a novel technique for detecting bacterial infection in insects
Authors: Killiny Nabil , Etxeberria Ed , Flores Alejandro Ponce , Blanco Pedro Gonzalez , Reyes Teresa Flores , Cabrera Luis Ponce 
Published: February 2019

AbstractTo prevent the spread of diseases in humans, animals or plants, determining whether potential vectors are infected is crucial. For example, early detection of the citrus disease Huanglongbing, which has been a scourge on the citrus industries around the world, is a critical need. This vector-borne disease is transmitted by Diaphorina citri, the Asian citrus psyllid, which carries the putative bacterial phytopathogen, Candidatus Liberibacter asiaticus (CLas). In this investigation, we introduced Laser-Induced Breakdown Spectroscopy (LIBS) to reveal key biochemical differences between CLas-infected and non-infected psyllids. The emission spectra captured from laser ablation of CLas-infected and healthy psyllids were processed through the principal component analysis (PCA) method and compared. Thirteen peaks from seven different elements were detected in D. citri. The t-test showed that CLas-infected D. citri were deficients in zinc, iron, copper, magnesium, calcium, and nitrogen. The PCA showed that LIBS can successfully differentiate between CLas-infected and healthy D. citri by comparing their elemental profile. In this work, we demonstrated a method that allows for a fast and precise compositional microanalysis of an insect vector which can contribute to the early detection of citrus huanglongbing
Standing task difficulty related increase in agonist-agonist and agonist-antagonist common inputs are driven by corticospinal and subcortical inputs respectively
Authors: Nandi Tulika , Hortobágyi Tibor , van Keeken Helco G. , Salem George J. , Lamoth Claudine J. C. 
Published: February 2019

AbstractIn standing, coordinated activation of lower extremity muscles can be simplified by common neural inputs to muscles comprising a functional synergy. We examined the effect of task difficulty on common inputs to agonist-agonist (AG-AG) pairs supporting direction specific reciprocal muscle control and agonist-antagonist (AG-ANT) pairs supporting stiffness control. Since excessive stiffness is energetically costly and limits the flexibility of responses to perturbations, compared to AG-ANT, we expected greater AG-AG common inputs and a larger increase with increasing task difficulty. We used coherence analysis to examine common inputs in three frequency ranges which reflect subcortical/spinal (0–5 and 6–15 Hz) and corticospinal inputs (6–15 and 16–40 Hz). Coherence was indeed higher in AG-AG compared to AG-ANT muscles in all three frequency bands, indicating a predilection for functional synergies supporting reciprocal rather than stiffness control. Coherence increased with increasing task difficulty, only in AG-ANT muscles in the low frequency band (0–5 Hz), reflecting subcortical inputs and only in AG-AG group in the high frequency band (16–40 Hz), reflecting corticospinal inputs. Therefore, common neural inputs to both AG-AG and AG-ANT muscles increase with difficulty but are likely driven by different sources of input to spinal alpha motor neurons.
Lower limb amputees undergo long-distance plasticity in sensorimotor functional connectivity
Authors: Bramati Ivanei E. , Rodrigues Erika C. , Simões Elington L. , Melo Bruno , Höfle Sebastian , Moll Jorge , Lent Roberto , Tovar-Moll Fernanda 
Published: February 2019

AbstractAmputation in adults is associated with an extensive remapping of cortical topography in primary and secondary sensorimotor areas. Here, we used tactile residual limb stimulation and 3T functional magnetic resonance imaging in humans to investigate functional connectivity changes in the sensorimotor network of patients with long-term lower limb traumatic amputations with phantom sensation, but without pain. We found a pronounced reduction of inter-hemispheric functional connectivity between homologous sensorimotor cortical regions in amputees, including the primary (S1) and secondary (S2) somatosensory areas, and primary (M1) and secondary (M2) motor areas. We additionally observed an intra-hemispheric increased functional connectivity between primary and secondary somatosensory regions, and between the primary and premotor areas, contralateral to amputation. These functional connectivity changes in specialized small-scale sensory-motor networks improve our understanding of the functional impact of lower limb amputation in the brain. Our findings in a selective group of patients with phantom limb sensations, but without pain suggest that disinhibition of neural inputs following traumatic limb amputation disrupts sensorimotor topology, unbalancing functional brain network organization. These findings step up the description of brain plasticity related with phantom sensations by showing that pain is not critical for sensorimotor network changes after peripheral injury.
The impact of estimated tumour purity on gene expression-based drug repositioning of Clear Cell Renal Cell Carcinoma samples
Authors: Koudijs Karel K. M. , Terwisscha van Scheltinga Anton G. T. , Böhringer Stefan , Schimmel Kirsten J. M. , Guchelaar Henk-Jan 
Published: February 2019

AbstractTo find new potentially therapeutic drugs against clear cell Renal Cell Carcinoma (ccRCC), within drugs currently prescribed for other diseases (drug repositioning), we previously searched for drugs which are expected to bring the gene expression of 500 + ccRCC samples from The Cancer Genome Atlas closer to that of healthy kidney tissue samples. An inherent limitation of this bulk RNA-seq data is that tumour samples consist of a varying mixture of cancerous and non-cancerous cells, which influences differential gene expression analyses. Here, we investigate whether the drug repositioning candidates are expected to target the genes dysregulated in ccRCC cells by studying the association with tumour purity. When all ccRCC samples are analysed together, the drug repositioning potential of identified drugs start decreasing above 80% estimated tumour purity. Because ccRCC is a highly vascular tumour, attributed to frequent loss of VHL function and subsequent activation of Hypoxia-Inducible Factor (HIF), we stratified the samples by observed activation of the HIF-pathway. After stratification, the association between estimated tumour purity and drug repositioning potential disappears for HIF-activated samples. This result suggests that the identified drug repositioning candidates specifically target the genes expressed by HIF-activated ccRCC tumour cells, instead of genes expressed by other cell types part of the tumour micro-environment.
Solid immersion microscopy images cells under cryogenic conditions with 12 nm resolution
Authors: Wang Lin , Bateman Benji , Zanetti-Domingues Laura C. , Moores Amy N. , Astbury Sam , Spindloe Christopher , Darrow Michele C. , Romano Maria , Needham Sarah R. , Beis Konstantinos , Rolfe Daniel J. , Clarke David T. , Martin-Fernandez Marisa L. 
Published: February 2019

AbstractSuper-resolution fluorescence microscopy plays a crucial role in our understanding of cell structure and function by reporting cellular ultrastructure with 20–30 nm resolution. However, this resolution is insufficient to image macro-molecular machinery at work. A path to improve resolution is to image under cryogenic conditions. This substantially increases the brightness of most fluorophores and preserves native ultrastructure much better than chemical fixation. Cryogenic conditions are, however, underutilised because of the lack of compatible high numerical aperture objectives. Here, using a low-cost super-hemispherical solid immersion lens (superSIL) and a basic set-up we achieve 12 nm resolution under cryogenic conditions, to our knowledge the best yet attained in cells using simple set-ups and/or commercial systems. By also allowing multicolour imaging, and by paving the way to total-internal-reflection fluorescence imaging of mammalian cells under cryogenic conditions, superSIL microscopy opens a straightforward route to achieve unmatched resolution on bacterial and mammalian cell samples.