bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intramolecular trimerization, a novel strategy for making multispecific antibodies with controlled orientation of the antigen binding domains
Authors: Alvarez-Cienfuegos Ana , Nuñez-Prado Natalia , Compte Marta , Cuesta Angel M. , Blanco-Toribio Ana , Harwood Seandean Lykke , Villate Maider , Merino Nekane , Bonet Jaume , Navarro Rocio , Muñoz-Briones Clara , Sørensen Karen Marie Juul , Mølgaard Kasper , Oliva Baldo , Sanz Laura , Blanco Francisco J. , Alvarez-Vallina Luis 
Published: June 2016

AbstractHere, we describe a new strategy that allows the rapid and efficient engineering of mono and multispecific trivalent antibodies. By fusing single-domain antibodies from camelid heavy-chain-only immunoglobulins (VHHs) to the N-terminus of a human collagen XVIII trimerization domain (TIEXVIII) we produced monospecific trimerbodies that were efficiently secreted as soluble functional proteins by mammalian cells. The purified VHH-TIEXVIII trimerbodies were trimeric in solution and exhibited excellent antigen binding capacity. Furthermore, by connecting with two additional glycine-serine-based linkers three VHH-TIEXVIII modules on a single polypeptide chain, we present an approach for the rational design of multispecific tandem trimerbodies with defined stoichiometry and controlled orientation. Using this technology we report here the construction and characterization of a tandem VHH-based trimerbody capable of simultaneously binding to three different antigens: carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR) and green fluorescence protein (GFP). Multispecific tandem VHH-based trimerbodies were well expressed in mammalian cells, had good biophysical properties and were capable of simultaneously binding their targeted antigens. Importantly, these antibodies were very effective in inhibiting the proliferation of human epidermoid carcinoma A431 cells. Multispecific VHH-based trimerbodies are therefore ideal candidates for future applications in various therapeutic areas.
Mobile phone imaging and cloud-based analysis for standardized malaria detection and reporting
Authors: Scherr Thomas F. , Gupta Sparsh , Wright David W. , Haselton Frederick R. 
Published: June 2016

AbstractRapid diagnostic tests (RDTs) have been widely deployed in low-resource settings. These tests are typically read by visual inspection and accurate record keeping and data aggregation remains a substantial challenge. A successful malaria elimination campaign will require new strategies that maximize the sensitivity of RDTs, reduce user error and integrate results reporting tools. In this report, an unmodified mobile phone was used to photograph RDTs, which were subsequently uploaded into a globally accessible database, REDCap and then analyzed three ways: with an automated image processing program, visual inspection and a commercial lateral flow reader. The mobile phone image processing detected 20.6 malaria parasites/microliter of blood, compared to the commercial lateral flow reader which detected 64.4 parasites/microliter. Experienced observers visually identified positive malaria cases at 12.5 parasites/microliter, but encountered reporting errors and false negatives. Visual interpretation by inexperienced users resulted in only an 80.2% true negative rate, with substantial disagreement in the lower parasitemia range. We have demonstrated that combining a globally accessible database, such as REDCap, with mobile phone based imaging of RDTs provides objective, secure, automated, data collection and result reporting. This simple combination of existing technologies would appear to be an attractive tool for malaria elimination campaigns.
Numerical Demultiplexing of Color Image Sensor Measurements via Non-linear Random Forest Modeling
Authors: Deglint Jason , Kazemzadeh Farnoud , Cho Daniel , Clausi David A. , Wong Alexander 
Published: June 2016

AbstractThe simultaneous capture of imaging data at multiple wavelengths across the electromagnetic spectrum is highly challenging, requiring complex and costly multispectral image devices. In this study, we investigate the feasibility of simultaneous multispectral imaging using conventional image sensors with color filter arrays via a novel comprehensive framework for numerical demultiplexing of the color image sensor measurements. A numerical forward model characterizing the formation of sensor measurements from light spectra hitting the sensor is constructed based on a comprehensive spectral characterization of the sensor. A numerical demultiplexer is then learned via non-linear random forest modeling based on the forward model. Given the learned numerical demultiplexer, one can then demultiplex simultaneously-acquired measurements made by the color image sensor into reflectance intensities at discrete selectable wavelengths, resulting in a higher resolution reflectance spectrum. Experimental results demonstrate the feasibility of such a method for the purpose of simultaneous multispectral imaging.
BcMtg2 is required for multiple stress tolerance, vegetative development and virulence in Botrytis cinerea
Authors: Shao Wenyong , Zhang Yu , Wang Jin , Lv Chiyuan , Chen Changjun 
Published: June 2016

AbstractInSaccharomyces cerevisiae, theMtg2gene encodes the Obg protein, which has an important function in assembling ribosomal subunits. However, little is known about the role of the Obg GTPase in filamentous fungi. In this study, we identified anMtg2ortholog,BcMtg2, inB. cinerea. TheBcMtg2deletion mutant showed a defect in spore production, conidial germination and sclerotial formation. Additionally, the mutant increased sensitivity to various environmental stresses. TheBcMtg2mutant exhibited dramatically decreased virulence on host plant tissues.BcMtg2mutant showed increased sensitivity to osmotic and oxidative stresses and to Congo red (cell wall stress agent). In the yeast complement assay, growth defects of yeast BY4741ΔMTG2 mutant were partly restored by genetic complementation ofBcMtg2under these environmental stresses. Additionally, compared with the parental strain and complement strain, theBcMtg2deletion mutant displayed a minor glycerol response to osmosis stress. These defective phenotypes were recovered in the complement strainΔBcMtg2C, which was created by adding the wild-typeBcMtg2gene to theΔBcMtg2mutant. The results of this study indicate thatBcMtg2has a necessary role in asexual development, environmental stress response and pathogenicity inB. cinerea.
Zolpidem is a potent stoichiometry-selective modulator of α1β3 GABAA receptors: evidence of a novel benzodiazepine site in the α1-α1 interface
Authors: Che Has Ahmad Tarmizi , Absalom Nathan , van Nieuwenhuijzen Petra S. , Clarkson Andrew N. , Ahring Philip K. , Chebib Mary 
Published: June 2016

AbstractZolpidem is not a typical GABAAreceptor hypnotic. Unlike benzodiazepines, zolpidem modulates tonic GABA currents in the rat dorsal motor nucleus of the vagus, exhibits residual effects in mice lacking the benzodiazepine binding site and improves speech, cognitive and motor function in human patients with severe brain injury. The receptor by which zolpidem mediates these effects is not known. In this study we evaluated binary α1β3 GABAAreceptors in either the 3α1:2β3 or 2α1:3β3 subunit stoichiometry, which differ by the existence of either an α1-α1 interface, or a β3-β3 interface, respectively. Both receptor stoichiometries are readily expressed inXenopusoocytes, distinguished from each other by using GABA, zolpidem, diazepam and Zn2+. At the 3α1:2β3 receptor, clinically relevant concentrations of zolpidem enhanced GABA in a flumazenil-sensitive manner. The efficacy of diazepam was significantly lower compared to zolpidem. No modulation by either zolpidem or diazepam was detected at the 2α1:3β3 receptor, indicating that the binding site for zolpidem is at the α1-α1 interface, a site mimicking the classical α1-γ2 benzodiazepine site. Activating α1β3 (3α1:2β3) receptors may, in part, mediate the physiological effects of zolpidem observed under distinct physiological and clinical conditions, constituting a potentially attractive drug target.
Risk of Band Keratopathy in Patients with End-Stage Renal Disease
Authors: Weng Shih-Feng , Jan Ren-Long , Chang Chun , Wang Jhi-Joung , Su Shih-Bin , Huang Chien-Cheng , Tseng Sung-Huei , Chang Yuh-Shin 
Published: June 2016

AbstractThis study is a retrospective, nationwide, matched cohort study to investigate the risk of band keratopathy following end-stage renal disease (ESRD). The study cohort included 94,039 ESRD on-dialysis patients identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), code 585 and registered between January 2000 to December 2009 at the Taiwan National Health Insurance Research Database. An age- and sex-matched control group comprised 94,039 patients selected from the Taiwan Longitudinal Health Insurance Database 2000. Information for each patient was collected from the index date until December 2011. In total, 230 ESRD patients and 26 controls had band keratopathy (P < 0.0001) during the follow-up period, indicating a significantly elevated risk of band keratopathy in the ESRD patients compared with controls (incidence rate ratio = 12.21, 95% confidence interval [CI] = 8.14–18.32). After adjustment for potential confounders including sarcoidosis, hyperparathyroidism, iridocyclitis and phthisis bulbi, ESRD patients were 11.56 times more likely to develop band keratopathy in the full cohort (adjusted HR = 11.56, 95% CI = 7.70–17.35). In conclusion, ESRD increases the risk of band keratopathy. Close interdisciplinary collaboration between nephrologists and ophthalmologists is important to deal with band keratopathy following ESRD and prevent visual acuity impairments.
A high-density genetic map and growth related QTL mapping in bighead carp (Hypophthalmichthys nobilis)
Authors: Fu Beide , Liu Haiyang , Yu Xiaomu , Tong Jingou 
Published: June 2016

AbstractGrowth related traits in fish are controlled by quantitative trait loci (QTL), but no QTL for growth have been detected in bighead carp (Hypophthalmichthys nobilis) due to the lack of high-density genetic map. In this study, an ultra-high density genetic map was constructed with 3,121 SNP markers by sequencing 117 individuals in a F1 family using 2b-RAD technology. The total length of the map was 2341.27 cM, with an average marker interval of 0.75 cM. A high level of genomic synteny between our map and zebrafish was detected. Based on this genetic map, one genome-wide significant and 37 suggestive QTL for five growth-related traits were identified in 6 linkage groups (i.e. LG3, LG11, LG15, LG18, LG19, LG22). The phenotypic variance explained (PVE) by these QTL varied from 15.4% to 38.2%. Marker within the significant QTL region was surrounded by CRP1 and CRP2, which played an important role in muscle cell division. These high-density map and QTL information provided a solid base for QTL fine mapping and comparative genomics in bighead carp.
N-terminal tetrapeptide T/SPLH motifs contribute to multimodal activation of human TRPA1 channel
Authors: Hynkova Anna , Marsakova Lenka , Vaskova Jana , Vlachova Viktorie 
Published: June 2016

AbstractHuman transient receptor potential ankyrin channel 1 (TRPA1) is a polymodal sensor implicated in pain, inflammation and itching. An important locus for TRPA1 regulation is the cytoplasmic N-terminal domain, through which various exogenous electrophilic compounds such as allyl-isothiocyanate from mustard oil or cinnamaldehyde from cinnamon activate primary afferent nociceptors. This major region is comprised of a tandem set of 17 ankyrin repeats (AR1-AR17), five of them contain a strictly conserved T/SPLH tetrapeptide motif, a hallmark of an important and evolutionarily conserved contribution to conformational stability. Here, we characterize the functional consequences of putatively stabilizing and destabilizing mutations in these important structural units and identify AR2, AR6 and AR11-13 to be distinctly involved in the allosteric activation of TRPA1 by chemical irritants, cytoplasmic calcium and membrane voltage. Considering the potential involvement of the T/SP motifs as putative phosphorylation sites, we also show that proline-directed Ser/Thr kinase CDK5 modulates the activity of TRPA1 and that T673 outside the AR-domain is its only possible target. Our data suggest that the most strictly conserved N-terminal ARs define the energetics of the TRPA1 channel gate and contribute to chemical-, calcium- and voltage-dependence.
Three-dimensional bioprinting using self-assembling scalable scaffold-free “tissue strands” as a new bioink
Authors: Yu Yin , Moncal Kazim K. , Li Jianqiang , Peng Weijie , Rivero Iris , Martin James A. , Ozbolat Ibrahim T. 
Published: June 2016

AbstractRecent advances in bioprinting have granted tissue engineers the ability to assemble biomaterials, cells and signaling molecules into anatomically relevant functional tissues or organ parts. Scaffold-free fabrication has recently attracted a great deal of interest due to the ability to recapitulate tissue biology by using self-assembly, which mimics the embryonic development process. Despite several attempts, bioprinting of scale-up tissues at clinically-relevant dimensions with closely recapitulated tissue biology and functionality is still a major roadblock. Here, we fabricate and engineer scaffold-free scalable tissue strands as a novel bioink material for robotic-assisted bioprinting technologies. Compare to 400 μm-thick tissue spheroids bioprinted in a liquid delivery medium into confining molds, near 8 cm-long tissue strands with rapid fusion and self-assemble capabilities are bioprinted in solid form for the first time without any need for a scaffold or a mold support or a liquid delivery medium and facilitated native-like scale-up tissues. The prominent approach has been verified using cartilage strands as building units to bioprint articular cartilage tissue.
Monogamy relation of multi-qubit systems for squared Tsallis-q entanglement
Authors: Yuan Guang-Ming , Song Wei , Yang Ming , Li Da-Chuang , Zhao Jun-Long , Cao Zhuo-Liang 
Published: June 2016

AbstractTsallis-q entanglement is a bipartite entanglement measure which is the generalization of entanglement of formation for q tending to 1. We first expand the range of q for the analytic formula of Tsallis-q entanglement. For "Equation missing", we prove the monogamy relation in terms of the squared Tsallis-q entanglement for an arbitrary multi-qubit systems. It is shown that the multipartite entanglement indicator based on squared Tsallis-q entanglement still works well even when the indicator based on the squared concurrence loses its efficacy. We also show that the μ-th power of Tsallis-q entanglement satisfies the monogamy or polygamy inequalities for any three-qubit state.
Insecticide resistance and nutrition interactively shape life-history parameters in German cockroaches
Authors: Jensen Kim , Ko Alexander E. , Schal Coby , Silverman Jules 
Published: June 2016

AbstractFitness-related costs of evolving insecticide resistance have been reported in a number of insect species, but the interplay between evolutionary adaptation to insecticide pressure and variable environmental conditions has received little attention. We provisioned nymphs from three German cockroach (Blattella germanicaL.) populations, which differed in insecticide resistance, with either nutritionally rich or poor (diluted) diet throughout their development. One population was an insecticide-susceptible laboratory strain; the other two populations originated from a field-collected indoxacarb-resistant population, which upon collection was maintained either with or without further selection with indoxacarb. We then measured development time, survival to the adult stage, adult body size, and results of a challenge with indoxacarb. Our results show that indoxacarb resistance and poor nutritional condition increased development time and lowered adult body size, with reinforcing interactions. We also found lower survival to the adult stage in the indoxacarb-selected population, which was exacerbated by poor nutrition. In addition, nutrition imparted a highly significant effect on indoxacarb susceptibility. This study exemplifies how poor nutritional condition can aggravate the life-history costs of resistance and elevate the detrimental effects of insecticide exposure, demonstrating how environmental conditions and resistance may interactively impact individual fitness and insecticide efficacy.
Bone Marrow Is a Reservoir for Cardiac Resident Stem Cells
Authors: Liu Na , Qi Xin , Han Zhibo , Liang Lu , Kong Deling , Han Zhongchao , Zhao Shihua , He Zuo-Xiang , Li Zongjin 
Published: June 2016

AbstractResident cardiac stem cells (CSCs) represent a responsive stem cell reservoir within the adult myocardium and have a significant function in myocardial homeostasis and injury. However, the distribution, origin, homing and possible therapeutic benefits of CSCs are still under discussion. Here we investigated whether bone marrow (BM) stem cells could contribute to repopulating the pool of CSCs in heart. The engraftment of BM cells in heart was detected at a low level after BM transplantation (BMT) and ischemia/reperfusion (I/R) could increase BM cells engraftment but not significant. We clarified that more than 50% CSCs are derived from BM and confirmed that BM-derived CSCs have similar characteristics with the host CSCs. Furthermore, we transplanted BM-derived CSCs into heart ischemia models and presented evidence for the first time that BM-derived CSCs can differentiate into cardiomyocytes in vivo. In conclusions, BM stem cells could be a potential back-up source of CSCs for restoring heart function after injury or maintaining homeostasis of CSCs.
Real-time spectroscopic monitoring of photocatalytic activity promoted by graphene in a microfluidic reactor
Authors: Li Yifan , Lin Beichen , Ge Likai , Guo Hongchen , Chen Xinyi , Lu Miao 
Published: June 2016

AbstractPhotocatalytic microreactors have been utilized as rapid, versatile platforms for the characterization of photocatalysts. In this work, a photocatalytic microreactor integrated with absorption spectroscopy was proposed for the real-time monitoring of photocatalytic activity using different catalysts. The validity of this method was investigated by the rapid screening on the photocatalytic performance of a titanium oxide (TiO2)-decorated graphene oxide (GO) sheet for the degradation of methylene blue under monochromatic visible irradiation. The sampling interval time could be minimized to 10 s for achieving real-time detection. The best photocatalytic activity was observed for an optimized TiO2/GO weight mixing ratio of 7:11, with a reaction rate constant up to 0.067 min−1. The addition of GO into TiO2 enhances photocatalytic activity and adsorption of MB molecules. The synthetic reaction rate constant was up to approximately 0.11 min−1, which was also the highest among the catalysts. The microreactor exhibited good sensitivity and reproducibility without weakening the performance of the photocatalysts. Consequently, the photocatalytic microreactor is promising as a simple, portable and rapid screening tool for new photocatalysts.
Loss of flotillin expression results in weakened desmosomal adhesion and Pemphigus vulgaris-like localisation of desmoglein-3 in human keratinocytes
Authors: Völlner Frauke , Ali Jawahir , Kurrle Nina , Exner Yvonne , Eming Rüdiger , Hertl Michael , Banning Antje , Tikkanen Ritva 
Published: June 2016

AbstractDesmosomes are adhesion plaques that mediate cell-cell adhesion in many tissues, including the epidermis, and generate mechanical resistance to tissues. The extracellular domains of desmosomal cadherin proteins, desmogleins and desmocollins, are required for the interaction with cadherins of the neighbouring cells, whereas their cytoplasmic tails associate with cytoplasmic proteins which mediate connection to intermediate filaments. Disruption of desmosomal adhesion by mutations, autoantibodies or bacterial toxins results in severe human disorders of e.g. the skin and the heart. Despite the vital role of desmosomes in various tissues, the details of their molecular assembly are not clear. We here show that the two members of the flotillin protein family directly interact with the cytoplasmic tails of desmogleins. Depletion of flotillins in human keratinocytes results in weakened desmosomal adhesion and reduced expression of desmoglein-3, most likely due to a reduction in the desmosomal pool due to increased turnover. In the absence of flotillins, desmoglein-3 shows an altered localisation pattern in the cell-cell junctions of keratinocytes, which is highly similar to the localisation observed upon treatment with pemphigus vulgaris autoantibodies. Thus, our data show that flotillins, which have previously been connected to the classical cadherins, are also of importance for the desmosomal cell adhesion.
Calcitonin attenuates cartilage degeneration and nociception in an experimental rat model of osteoarthritis: role of TGF-β in chondrocytes
Authors: Wen Zhi-Hong , Tang Chi-Chieh , Chang Yi-Chen , Huang Shi-Ying , Lin Yen-You , Hsieh Shih-Peng , Lee Hsin-Pai , Lin Sung-Chun , Chen Wu-Fu , Jean Yen-Hsuan 
Published: June 2016

AbstractWe investigated the role of the calcitonin (Miacalcin) in the progression of osteoarthritis (OA) and in nociceptive behavior in an experimental rat model of OA and osteoporosis. OA was induced by anterior cruciate ligament transection (ACLT) of the right knee and by bilateral ovariectomy (OVX) in Wistar rats. Nociceptive behaviors (secondary mechanical allodynia and weight-bearing distribution of the hind paws) were analyzed prior to surgery and every week, beginning at 12 weeks after surgery, up to 20 weeks. At 20 weeks, histopathological studies were performed on the cartilage of the knee joints. Immunohistochemical analysis was performed to examine the effect of calcitonin on transforming growth factor (TGF)-β1 expression in articular cartilage chondrocytes. Rats subjected to ACLT + OVX surgery showed obvious OA changes in the joints. Animals subjected to ACLT + OVX and treated with calcitonin showed significantly less cartilage degeneration and improved nociceptive tests compared with animals subjected to ACLT + OVX surgeries alone. Moreover, calcitonin increased TGF-β1 expression in chondrocytes in ACLT + OVX-affected cartilage. Subcutaneous injection of calcitonin (1) attenuated the development of OA, (2) concomitantly reduced nociception, and (3) modulated chondrocyte metabolism, possibly by increasing cellular TGF-β1 expression.
Fabrication of Laser-reduced Graphene Oxide in Liquid Nitrogen Environment
Authors: Guan Y. C. , Fang Y. W. , Lim G. C. , Zheng H. Y. , Hong M. H. 
Published: June 2016

AbstractPorous structure of reduced graphene oxide (rGO) plays an important role in developing flexible graphene-based devices. In this work, we report a novel methodology for reduction of freestanding graphite oxide (GO) sheet by picosecond pulse laser direct writing in liquid nitrogen. Non-agglomerate and porous structure of rGO is fabricated successfully due to frozen effect during laser processing. Compared with laser-irradiated rGO developed in N2 gas at ambient environment, the frozen rGO developed in liquid N2 shows better ordered structure with less defects, crack-free morphology as well as better electron supercapacitor performance including 50–60 Ω/sq in sheet electrical resistance. Mechanism of cryotemperature photoreduction GO is also discussed.