bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell-type specific potent Wnt signaling blockade by bispecific antibody
Authors: Lee Nam-Kyung , Zhang Yafeng , Su Yang , Bidlingmaier Scott , Sherbenou Daniel W. , Ha Kevin D. , Liu Bin 
Published: January 2018

AbstractCell signaling pathways are often shared between normal and diseased cells. How to achieve cell type-specific, potent inhibition of signaling pathways is a major challenge with implications for therapeutic development. Using the Wnt/β-catenin signaling pathway as a model system, we report here a novel and generally applicable method to achieve cell type-selective signaling blockade. We constructed a bispecific antibody targeting the Wnt co-receptor LRP6 (the effector antigen) and a cell type-associated antigen (the guide antigen) that provides the targeting specificity. We found that the bispecific antibody inhibits Wnt-induced reporter activities with over one hundred-fold enhancement in potency, and in a cell type-selective manner. Potency enhancement is dependent on the expression level of the guide antigen on the target cell surface and the apparent affinity of the anti-guide antibody. Both internalizing and non-internalizing guide antigens can be used, with internalizing bispecific antibody being able to block signaling by all ligands binding to the target receptor due to its removal from the cell surface. It is thus feasible to develop bispecific-based therapeutic strategies that potently and selectively inhibit signaling pathways in a cell type-selective manner, creating opportunity for therapeutic targeting.
Transcriptomic signatures of cellular and humoral immune responses in older adults after seasonal influenza vaccination identified by data-driven clustering
Authors: Voigt Emily A. , Grill Diane E. , Zimmermann Michael T. , Simon Whitney L. , Ovsyannikova Inna G. , Kennedy Richard B. , Poland Gregory A. 
Published: January 2018

AbstractPBMC transcriptomes after influenza vaccination contain valuable information about factors affecting vaccine responses. However, distilling meaningful knowledge out of these complex datasets is often difficult and requires advanced data mining algorithms. We investigated the use of the data-driven Weighted Gene Correlation Network Analysis (WGCNA) gene clustering method to identify vaccine response-related genes in PBMC transcriptomic datasets collected from 138 healthy older adults (ages 50–74) before and after 2010–2011 seasonal trivalent influenza vaccination. WGCNA separated the 14,197 gene dataset into 15 gene clusters based on observed gene expression patterns across subjects. Eight clusters were strongly enriched for genes involved in specific immune cell types and processes, including B cells, T cells, monocytes, platelets, NK cells, cytotoxic T cells, and antiviral signaling. Examination of gene cluster membership identified signatures of cellular and humoral responses to seasonal influenza vaccination, as well as pre-existing cellular immunity. The results of this study illustrate the utility of this publically available analysis methodology and highlight genes previously associated with influenza vaccine responses (e.g., CAMK4, CD19), genes with functions not previously identified in vaccine responses (e.g., SPON2, MATK, CST7), and previously uncharacterized genes (e.g. CORO1C, C8orf83) likely related to influenza vaccine-induced immunity due to their expression patterns.
Gender-specific association of early age-related macular degeneration with systemic and genetic factors in a Japanese population
Authors: Sasaki Mariko , Harada Sei , Kawasaki Yumiko , Watanabe Miki , Ito Hidemi , Tanaka Hideo , Takeuchi Ayano , Tsubota Kazuo , Takebayashi Toru , Nishiwaki Yuji , Kawasaki Ryo 
Published: January 2018

AbstractThe Tsuruoka Metabolomics Cohort Study included subjects aged 35–74 years from participants in annual health check-up programs in Tsuruoka, Japan. The gender-specific associations of early age-related macular degeneration (AMD) with systemic and genetic factors was assessed cross-sectionally. Of these, 3,988 subjects had fundus photographs of sufficient quality, and early AMD was present in 12.3% and 10.3% of men and women, respectively. In men, higher levels of high-density lipoprotein cholesterol and lower levels of triglycerides were associated with increased odds of having early AMD after adjusting for potential risk factors (for each 1 mmol/L increase, odds ratio [OR]: 1.61 and 0.78, 95% confidence interval [CI]: 1.17–2.23 and 0.64–0.96, respectively). In women, higher levels of total cholesterol and low-density lipoprotein cholesterol were associated with increased risk of having early AMD (OR: 1.21 and 1.26, 95% CI: 1.01–1.44 and 1.03–1.53, respectively). Sub-analysis demonstrated that women with ARMS2 A69S polymorphisms had a stronger risk for early AMD (OR: 3.25, 95% CI: 2.10–5.04) than men (OR: 1.65, 95% CI: 1.02–2.69). Differential associations of early AMD with both systemic and genetic factors by sex were demonstrated in a Japanese cohort, which suggests that disease process of early AMD could be different by sex.
Europe’s lost forests: a pollen-based synthesis for the last 11,000 years
Authors: Roberts N. , Fyfe R. M. , Woodbridge J. , Gaillard M.-J. , Davis B. A. S. , Kaplan J. O. , Marquer L. , Mazier F. , Nielsen A. B. , Sugita S. , Trondman A.-K. , Leydet M. 
Published: January 2018

Abstract8000 years ago, prior to Neolithic agriculture, Europe was mostly a wooded continent. Since then, its forest cover has been progressively fragmented, so that today it covers less than half of Europe’s land area, in many cases having been cleared to make way for fields and pasture-land. Establishing the origin of Europe’s current, more open land-cover mosaic requires a long-term perspective, for which pollen analysis offers a key tool. In this study we utilise and compare three numerical approaches to transforming pollen data into past forest cover, drawing on >100014C-dated site records. All reconstructions highlight the different histories of the mixed temperate and the northern boreal forests, with the former declining progressively since ~6000 years ago, linked to forest clearance for agriculture in later prehistory (especially in northwest Europe) and early historic times (e.g. in north central Europe). In contrast, extensive human impact on the needle-leaf forests of northern Europe only becomes detectable in the last two millennia and has left a larger area of forest in place. Forest loss has been a dominant feature of Europe’s landscape ecology in the second half of the current interglacial, with consequences for carbon cycling, ecosystem functioning and biodiversity.
Genome-wide identification and characterization of SPL transcription factor family and their evolution and expression profiling analysis in cotton
Authors: Cai Caiping , Guo Wangzhen , Zhang Baohong 
Published: January 2018

AbstractPlant specific transcription factors, SQUAMOSA promoter-binding protein-like (SPL), are involved in many biological processes. However, no systematical study has been reported in cotton. In this study, a total of 177 SPL genes were identified, including 29, 30, 59 and 59 SPLs in Gossypium arboreum, G. raimondii, G. barbadense, and G. hirsutum, respectively. These SPL genes were classified into eight phylogenetical groups. The gene structure, conserved motif, and clustering were highly conserved within each orthologs. Two zinc finger-like structures (Cys3His and Cys2HisCys) and NLS segments were existed in all GrSPLs. Segmental duplications play important roles in SPL family expansion, with 20 genes involved in segmental duplications and 2 in tandem duplications, and ten ortholog pairs in syntenic regions between G. raimondii and A. thaliana. Several putative cis-elements, involved in light, stresses and phytohormones response, were found in the promoter regions of GhSPLs, suggesting that plant responses to those environmental changes may be induced through targeting SPL transcription factors. RNA-seq analysis shows that SPL genes were differentially expressed in cotton; some were highly expressed during fiber initiation and early development. Comparing with other plants, SPL genes show subfunctionalization, lost and/or gain functions in cotton during long-term domestication and evolution.
Biophysical feedbacks mediate carbonate chemistry in coastal ecosystems across spatiotemporal gradients
Authors: Silbiger Nyssa J. , Sorte Cascade J. B. 
Published: January 2018

AbstractOcean acidification (OA) projections are primarily based on open ocean environments, despite the ecological importance of coastal systems in which carbonate dynamics are fundamentally different. Using temperate tide pools as a natural laboratory, we quantified the relative contribution of community composition, ecosystem metabolism, and physical attributes to spatiotemporal variability in carbonate chemistry. We found that biological processes were the primary drivers of local pH conditions. Specifically, non-encrusting producer-dominated systems had the highest and most variable pH environments and the highest production rates, patterns that were consistent across sites spanning 11° of latitude and encompassing multiple gradients of natural variability. Furthermore, we demonstrated a biophysical feedback loop in which net community production increased pH, leading to higher net ecosystem calcification. Extreme spatiotemporal variability in pH is, thus, both impacting and driven by biological processes, indicating that shifts in community composition and ecosystem metabolism are poised to locally buffer or intensify the effects of OA.
Highly conserved molecular pathways, including Wnt signaling, promote functional recovery from spinal cord injury in lampreys
Authors: Herman Paige E. , Papatheodorou Angelos , Bryant Stephanie A. , Waterbury Courtney K. M. , Herdy Joseph R. , Arcese Anthony A. , Buxbaum Joseph D. , Smith Jeramiah J. , Morgan Jennifer R. , Bloom Ona 
Published: January 2018

AbstractIn mammals, spinal cord injury (SCI) leads to dramatic losses in neurons and synaptic connections, and consequently function. Unlike mammals, lampreys are vertebrates that undergo spontaneous regeneration and achieve functional recovery after SCI. Therefore our goal was to determine the complete transcriptional responses that occur after SCI in lampreys and to identify deeply conserved pathways that promote regeneration. We performed RNA-Seq on lamprey spinal cord and brain throughout the course of functional recovery. We describe complex transcriptional responses in the injured spinal cord, and somewhat surprisingly, also in the brain. Transcriptional responses to SCI in lampreys included transcription factor networks that promote peripheral nerve regeneration in mammals such as Atf3 and Jun. Furthermore, a number of highly conserved axon guidance, extracellular matrix, and proliferation genes were also differentially expressed after SCI in lampreys. Strikingly, ~3% of differentially expressed transcripts belonged to the Wnt pathways. These included members of the Wnt and Frizzled gene families, and genes involved in downstream signaling. Pharmacological inhibition of Wnt signaling inhibited functional recovery, confirming a critical role for this pathway. These data indicate that molecular signals present in mammals are also involved in regeneration in lampreys, supporting translational relevance of the model.
Speed-related activation in the mesolimbic dopamine system during the observation of driver-view videos
Authors: Sakai Hiroyuki , Ando Takafumi , Sadato Norihiro , Uchiyama Yuji 
Published: January 2018

AbstractDespite the ubiquity and importance of speeding offenses, there has been little neuroscience research regarding the propensity for speeding among vehicle drivers. In the current study, as a first attempt, we examined the hypothesis that visual inputs during high-speed driving would activate the mesolimbic dopaminergic system that plays an important role in mediating motivational craving. To this end, we used functional magnetic resonance imaging to identify speed-related activation changes in mesolimbic dopaminergic regions during the observation of driver-view videos in two groups that differed in self-reported speeding propensity. Results revealed, as we expected, greater activation in the ventral tegmental area (VTA) in response to driver-view videos with higher speed. Contrary to our expectation, however, we found no significant between-group difference in speed-related activation changes in mesolimbic dopaminergic regions. Instead, an exploratory psychophysiological interaction analysis found that self-reported speeding propensity was associated with speed-related functional coupling between the VTA and the right intraparietal sulcus. Further validation of our hypothesis will require future studies examining associations between speed-related activation in the mesolimbic dopaminergic system and individual differences in speeding propensity, using a more reliable measure of actual speeding propensity in real traffic.
Interference induced enhancement of magneto-optical Kerr effect in ultrathin magnetic films
Authors: Sumi Satoshi , Awano Hiroyuki , Hayashi Masamitsu 
Published: January 2018

AbstractWe have studied the magneto-optical spectra of ultrathin magnetic films deposited on Si substrates coated with an oxide layer (SiOx). We find that the Kerr rotation angle and the ellipticity of ~1 nm thick CoFeB thin films, almost transparent to visible light, show a strong dependence on the thickness of the SiOx layer. The Kerr signal from the 1 nm CoFeB thin film can be larger than that of ~100 nm thick CoFeB films for a given SiOx thickness and light wavelength. The enhancement of the Kerr signal occurs when optical interference takes place within the SiOx layer. Interestingly, under such resonance condition, the measured Kerr signal is in some cases larger than the estimation despite the good agreement of the measured and calculated reflection amplitude. We infer the discrepancy originates from interface states that are distinct from the bulk characteristics. These results show that optical interference effect can be utilized to study the magneto-optical properties of ultrathin films.
Controlled dynamic screening of excitonic complexes in 2D semiconductors
Authors: Klots Andrey R. , Weintrub Benjamin , Prasai Dhiraj , Kidd Daniel , Varga Kalman , Velizhanin Kirill A. , Bolotin Kirill I. 
Published: January 2018

AbstractWe report a combined theoretical/experimental study of dynamic screening of excitons in media with frequency-dependent dielectric functions. We develop an analytical model showing that interparticle interactions in an exciton are screened in the range of frequencies from zero to the characteristic binding energy depending on the symmetries and transition energies of that exciton. The problem of the dynamic screening is then reduced to simply solving the Schrodinger equation with an effectively frequency-independent potential. Quantitative predictions of the model are experimentally verified using a test system: neutral, charged and defect-bound excitons in two-dimensional monolayer WS2, screened by metallic, liquid, and semiconducting environments. The screening-induced shifts of the excitonic peaks in photoluminescence spectra are in good agreement with our model.
Localization and function of neurosecretory protein GM, a novel small secretory protein, in the chicken hypothalamus
Authors: Shikano Kenshiro , Bessho Yuki , Kato Masaki , Iwakoshi-Ukena Eiko , Taniuchi Shusuke , Furumitsu Megumi , Tachibana Tetsuya , Bentley George E. , Kriegsfeld Lance J. , Ukena Kazuyoshi 
Published: January 2018

AbstractRecently, we discovered a novel cDNA encoding the precursor of a small secretory protein, neurosecretory protein GL (NPGL), in the hypothalamic infundibulum of chickens. NPGL plays an important role in the regulation of growth and feeding. A database search indicated that the NPGL gene has a paralogous gene: neurosecretory protein GM (NPGM), also in chickens. We identified cDNA encoding the NPGM precursor in chickens. Morphological analysis showed that NPGM-containing cells are specifically localized in the medial mammillary nucleus (MM) and infundibular nucleus (IN) in the hypothalamus. In addition, we found that NPGM and NPGL are co-localized, especially in the MM. The expression levels of NPGM mRNA gradually decreased during post-hatch development, in contrast to those of NPGL mRNA. Moreover, we investigated the relationship between NPGM and other known factors. NPGM was found to be produced in histaminergic neurons in the MM. NPGM and histidine decarboxylase, a histamine-producing enzyme, displayed similar expression patterns during post-hatch development. Acute intracerebroventricular injection of NPGM decreased food intake, similar to the effect of histamine. To our knowledge, this is the first report of the localization and function of NPGM in the brain of vertebrates. These results will further advance the understanding mechanisms underlying energy homeostasis.
Transcriptome profile of NO-induced Arabidopsis transcription factor genes suggests their putative regulatory role in multiple biological processes
Authors: Imran Qari Muhammad , Hussain Adil , Lee Sang-Uk , Mun Bong-Gyu , Falak Noreen , Loake Gary J. , Yun Byung-Wook 
Published: January 2018

AbstractTFs are important proteins regulating plant responses during environmental stresses. These insults typically induce changes in cellular redox tone driven in part by promoting the production of reactive nitrogen species (RNS). The main source of these RNS is nitric oxide (NO), which serves as a signalling molecule, eliciting defence and resistance responses. To understand how these signalling molecules regulate key biological processes, we performed a large scale S-nitrosocysteine (CySNO)-mediated RNA-seq analysis. The DEGs were analysed to identify potential regulatory TFs. We found a total of 673 (up- and down-regulated) TFs representing a broad range of TF families. GO-enrichment and MapMan analysis suggests that more than 98% of TFs were mapped to the Arabidopsis thaliana genome and classified into pathways like hormone signalling, protein degradation, development, biotic and abiotic stress, etc. A functional analysis of three randomly selected TFs, DDF1, RAP2.6, and AtMYB48 identified a regulatory role in plant growth and immunity. Loss-of-function mutations within DDF1 and RAP2.6 showed compromised basal defence and effector triggered immunity, suggesting their positive role in two major plant defence systems. Together, these results imply an important data representing NO-responsive TFs that will help in exploring the core mechanisms involved in biological processes in plants.
The effects of Antibody Engineering CH and CL in Trastuzumab and Pertuzumab recombinant models: Impact on antibody production and antigen-binding
Authors: Lua Wai-Heng , Ling Wei-Li , Yeo Joshua Yi , Poh Jun-Jie , Lane David Philip , Gan Samuel Ken-En 
Published: January 2018

AbstractCurrent therapeutic antibodies such as Trastuzumab, are typically of the blood circulatory IgG1 class (Cκ/ CHγ1). Due to the binding to Her2 also present on normal cell surfaces, side effects such as cardiac failure can sometimes be associated with such targeted therapy. Using antibody isotype swapping, it may be possible to reduce systemic circulation through increased tissue localization, thereby minimising unwanted side effects. However, the effects of such modifications have yet to be fully characterized, particularly with regards to their biophysical properties in antigen binding. To do this, we produced all light and heavy chain human isotypes/subtypes recombinant versions of Trastuzumab and Pertuzumab, and studied them with respect to recombinant production and Her2 binding. Our findings show that while the light chain constant region changes have no major effects on production or Her2 binding, some heavy chain isotypes, in particularly, IgM and IgD isotypes, can modulate antigen binding. This study thus provides the groundwork for such isotype modifications to be performed in the future to yield therapeutics of higher efficacy and efficiency.
Synaptic localisation of SRF coactivators, MKL1 and MKL2, and their role in dendritic spine morphology
Authors: Kaneda Marisa , Sakagami Hiroyuki , Hida Yamato , Ohtsuka Toshihisa , Satou Natsumi , Ishibashi Yuta , Fukuchi Mamoru , Krysiak Anna , Ishikawa Mitsuru , Ihara Daisuke , Kalita Katarzyna , Tabuchi Akiko 
Published: January 2018

AbstractThe megakaryoblastic leukaemia (MKL) family are serum response factor (SRF) coactivators, which are highly expressed in the brain. Accordingly, MKL plays important roles in dendritic morphology, neuronal migration, and brain development. Further, nucleotide substitutions in the MKL1 and MKL2 genes are found in patients with schizophrenia and autism spectrum disorder, respectively. Thus, studies on the precise synaptic localisation and function of MKL in neurons are warranted. In this study, we generated and tested new antibodies that specifically recognise endogenously expressed MKL1 and MKL2 proteins in neurons. Using these reagents, we biochemically and immunocytochemically show that MKL1 and MKL2 are localised at synapses. Furthermore, shRNA experiments revealed that postsynaptic deletion of MKL1 or MKL2 reduced the percentage of mushroom- or stubby-type spines in cultured neurons. Taken together, our findings suggest that MKL1 and MKL2 are present at synapses and involved in dendritic spine maturation. This study may, at least in part, contribute to better understanding of the molecular mechanisms underlying MKL-mediated synaptic plasticity and neurological disorders.
The relationship of dietary fish intake to diabetic retinopathy and retinal vascular caliber in patients with type 2 diabetes
Authors: Chua Jacqueline , Chia Ai-Ru , Chee Miao Li , Man Ryan Eyn Kidd , Tan Gavin Siew Wei , Lamoureux Ecosse L. , Wong Tien Yin , Chong Mary Foong-Fong , Schmetterer Leopold 
Published: January 2018

AbstractIn this cross-sectional study, we evaluated the association of dietary fish intake with varying severity of diabetic retinopathy (DR) and retinal vascular caliber in Asians with type 2 diabetes mellitus. 357 Asians (median age: 58 years; 31% women; 78% Chinese) were recruited from a tertiary eye care institution in Singapore. Fish consumption was evaluated using a validated food frequency questionnaire. Digital retinal photographs assessed for DR severity and retinal vascular caliber. Ordered logistic and linear regression models were used to investigate the association of fish intake with DR severity and vascular caliber. Increasing frequency of fish consumption was significantly associated with lower odds of having severe DR (odds ratio [OR] = 0.91, 95% CI: 0.84–0.99 per 1-unit increase of fish intake; P = 0.038). Among those with no retinopathy, persons in quartile 4 fish intake had a wider retinal vascular caliber for arteriolar (β = 22.27 µm, 95% CI: 12.64–31.90; P-trend < 0.001) and venular (β = 32.00 µm, 95% CI: 17.56–46.43; P-trend < 0.001), than those in quartile 1 fish intake. Persons with higher fish intake had a decreased likelihood of having severe DR. In diabetics without retinopathy, higher fish intake was associated with wider retinal vascular caliber. Future research is needed to reinforce the direction of the casualty.