bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brief Report: Inhibition of miR-145 Enhances Reprogramming of Human Dermal Fibroblasts to Induced Pluripotent Stem Cells
Authors: Barta Tomas , Peskova Lucie , Collin Joseph , Montaner David , Neganova Irina , Armstrong Lyle , Lako Majlinda 
Published: September 2015

Abstract
MicroRNA (miRNAs) are short noncoding RNA molecules involved in many cellular processes and shown to play a key role in somatic cell induced reprogramming. We performed an array based screening to identify candidates that are differentially expressed between dermal skin fibroblasts (DFs) and induced pluripotent stem cells (iPSCs). We focused our investigations on miR-145 and showed that this candidate is highly expressed in DFs relative to iPSCs and significantly downregulated during reprogramming process. Inhibition of miR-145 in DFs led to the induction of “cellular plasticity” demonstrated by: (a) alteration of cell morphology associated with downregulation of mesenchymal and upregulation of epithelial markers; (b) upregulation of pluripotency-associated genes including SOX2, KLF4, C-MYC; (c) downregulation of miRNA let-7b known to inhibit reprogramming; and (iv) increased efficiency of reprogramming to iPSCs in the presence of reprogramming factors. Together, our results indicate a direct functional link between miR-145 and molecular pathways underlying reprogramming of somatic cells to iPSCs.
Control of carbon flux to glutamate excretion in Klebsiella pneumoniae: the role of the indigenous plasmid and its encoded isocitrate dehydrogenase
Authors: El-Mansi Mansi , Trappey Francois , Clark Ewan , Campbell Malcolm 
Published: September 2015

Abstract
Klebsiella pneumoniae (NCTC, CL687/80) harbors a large indigenous plasmid (pC3), which in addition to encoding for citrate utilization, proline synthesis and glutamate excretion, it uniquely carries the structural gene (icd); encoding isocitrate dehydrogenase (ICDH). Flux analysis revealed that ICDH, despite its role in the generation of NADPH required for glutamate dehydrogenase, is not rate-limiting (controlling) in central metabolism as evidenced by a negative flux control coefficient and an adverse effect of overexpression (14-fold) on glutamate excretion. More significantly, however, this paper presents, for the first time, clear evidence that the accumulation of glutamate and its subsequent excretion is associated with the C3 plasmid-encoded regulatory elements, which trigger a shift-down in the activity of α-ketoglutarate dehydrogenase, both in the K. pneumoniae parental strain as well as in the E. coli exconjugants strains. This finding opens the door for the exploitation of regulatory elements as a tool for manipulating flux in microbial cell factories.
Testamentary Archeology in Late-Victorian Ontario: William Martin's Little, Posthumous Legal System
Authors: Baker G. Blaine 
Published: September 2015

AbstractThis is a 'will-in-context' study of a Toronto bequest of the 1880s that shows how a testator's ideological commitment to freedom of willing and his retention of high-powered legal talent to actualize that commitment were derailed by a hapless or avaricious executor, unpredictable real-estate markets, a lethargic court, and eccentric beneficiaries. It also suggests that self-made private law like contracts, trusts, and wills may be as doctrinally, textually, or administratively contradictory, indeterminate, or unpredictable as state-made public or regulatory law has often been shown to be.
Pre-operative serum alkaline phosphatase as a predictive indicator of post-operative hypocalcaemia in patients undergoing total thyroidectomy
Authors: Miah M S , Mahendran S , Mak C , Leese G , Smith D 
Published: September 2015

AbstractObjective:This study aimed to evaluate whether a pre-operative elevated serum alkaline phosphatase level is a potential predictor of post-operative hypocalcaemia after total thyroidectomy.Methods:Data was retrospectively collected from the case notes of patients who had undergone total thyroidectomy. Patients were divided into Graves’ disease and non-Graves’ groups. Pre-operative and post-operative biochemical markers, including serum calcium, alkaline phosphatase and parathyroid hormone levels, were reviewed.Results:A total of 225 patients met the inclusion criteria. Graves’ disease was the most common indication (n = 134; 59.5 per cent) for thyroidectomy. Post-operative hypocalcaemia developed in 48 patients (21.3 per cent) and raised pre-operative serum alkaline phosphatase was noted in 94 patients (41.8 per cent). Raised pre-operative serum alkaline phosphatase was significantly associated with post-operative hypocalcaemia, particularly in Graves’ disease patients (p< 0.05).Conclusion:Pre-operative serum alkaline phosphatase measurements help to predict post-thyroidectomy hypocalcaemia, especially in patients who do not develop hypoparathyroidism. Ascertaining the pre-operative serum alkaline phosphatase level in patients undergoing total thyroidectomy may help surgeons to identify at-risk patients.
Emergency department syndromic surveillance providing early warning of seasonal respiratory activity in England
Authors: HUGHES H. E. , MORBEY R. , HUGHES T. C. , LOCKER T. E. , PEBODY R. , GREEN H. K. , ELLIS J. , SMITH G. E. , ELLIOT A. J. 
Published: September 2015

SUMMARYSeasonal respiratory infections place an increased burden on health services annually. We used a sentinel emergency department syndromic surveillance system to understand the factors driving respiratory attendances at emergency departments (EDs) in England. Trends in different respiratory indicators were observed to peak at different points during winter, with further variation observed in the distribution of attendances by age. Multiple linear regression analysis revealed acute respiratory infection and bronchitis/bronchiolitis ED attendances in patients aged 1–4 years were particularly sensitive indicators for increasing respiratory syncytial virus activity. Using near real-time surveillance of respiratory ED attendances may provide early warning of increased winter pressures in EDs, particularly driven by seasonal pathogens. This surveillance may provide additional intelligence about different categories of attendance, highlighting pressures in particular age groups, thereby aiding planning and preparation to respond to acute changes in EDs, and thus the health service in general.
Comparison of flavonoid contents and antioxidant activities of Vicia species
Authors: Lee Kyung Jun , Lee Jung-Ro , Kim Hyo-Jeong , Raveendar Sebastin , Lee Gi-An , Jeon Young-Ah , Park Eunseong , Ma Kyung-Ho , Lee Sok-Young , Chung Jong-Wook 
Published: September 2015

A total of 27 accessions from ten Vicia species were investigated for flavonoid contents, total polyphenol contents, and DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS [2,2′-azinobis(3-ethylbenzothiazoline 6-sulfonic acid)] free radical-scavenging activities. The results revealed that NAC17 (V. monantha) and NAC14 (V. hyrcanica) had the highest total flavonoid content (1.42 ± 0.09 mg/g) and total polyphenol content [124.2 ± 0.5 μg/gallic acid equivalents (GAE) mg], respectively. Among four flavonoids, naringenin was detected at high concentrations in Vicia species. The DPPH and ABTS assays showed values in the range of 57.2 (IC50) (NAC13, V. faba) to 6530.0 (IC50) (NAC24, V. sativa subsp. nigra) and 19.1 μg/Trolox mg (NAC7, V. cracca) to 253.4 μg/Trolox mg (NAC13, V. faba), respectively. Among ten Vicia species, V. monantha and V. hyrcanica had the highest flavonoid content (1.31 ± 0.09 mg/g) and total polyphenol content (116.5 ± 2.0 μg/GAE mg), respectively. The highest antioxidant activity was detected in V. faba. These results will expand the flavonoid database and provide valuable information on Vicia species for the development of functional foods or feed-additive resources.
A streamlined search technology for identification of synergistic drug combinations
Authors: Weiss Andrea , Berndsen Robert H. , Ding Xianting , Ho Chih-Ming , Dyson Paul J. , van den Bergh Hubert , Griffioen Arjan W. , Nowak-Sliwinska Patrycja 
Published: September 2015

AbstractA major key to improvement of cancer therapy is the combination of drugs. Mixing drugs that already exist on the market may offer an attractive alternative. Here we report on a new model-based streamlined feedback system control (s-FSC) method, based on a design of experiment approach, for rapidly finding optimal drug mixtures with minimal experimental effort. We tested combinations in an in vitro assay for the viability of a renal cell adenocarcinoma (RCC) cell line, 786-O. An iterative cycle of in vitro testing and s-FSC analysis was repeated a few times until an optimal low dose combination was reached. Starting with ten drugs that target parallel pathways known to play a role in the development and progression of RCC, we identified the best overall drug combination, being a mixture of four drugs (axitinib, erlotinib, dasatinib and AZD4547) at low doses, inhibiting 90% of cell viability. The removal of AZD4547 from the optimized drug combination resulted in 80% of cell viability inhibition, while still maintaining the synergistic interaction. These optimized drug combinations were significantly more potent than monotherapies of all individual drugs (p < 0.001, CI < 0.3).
Full-color structured illumination optical sectioning microscopy
Authors: Qian Jia , Lei Ming , Dan Dan , Yao Baoli , Zhou Xing , Yang Yanlong , Yan Shaohui , Min Junwei , Yu Xianghua 
Published: September 2015

AbstractIn merits of super-resolved resolution and fast speed of three-dimensional (3D) optical sectioning capability, structured illumination microscopy (SIM) has found variety of applications in biomedical imaging. So far, most SIM systems use monochrome CCD or CMOS cameras to acquire images and discard the natural color information of the specimens. Although multicolor integration scheme are employed, multiple excitation sources and detectors are required and the spectral information is limited to a few of wavelengths. Here, we report a new method for full-color SIM with a color digital camera. A data processing algorithm based on HSV (Hue, Saturation and Value) color space is proposed, in which the recorded color raw images are processed in the Hue, Saturation, Value color channels and then reconstructed to a 3D image with full color. We demonstrated some 3D optical sectioning results on samples such as mixed pollen grains, insects, micro-chips and the surface of coins. The presented technique is applicable to some circumstance where color information plays crucial roles, such as in materials science and surface morphology.
Hepatitis C-like viruses are produced in cells from rabbit and hare DNA
Authors: Silva Eliane , Osório Hugo , Thompson Gertrude 
Published: September 2015

AbstractHepatitis C virus (HCV), a major causative agent of acute and chronic liver disease, belongs to the Flaviviridæ family and contains a single-strand positive-sense RNA genome, which upon virus entry and uncoating, functions as mRNAs and thus can be directly translated into proteins by host cell machinery. To date the HCV origin remains unclear and HCV life cycle and pathogenesis are not enlightened processes due to the absence of HCV efficient cell cultures systems or animals models. Here we show that rabbit and hare HCV-like viruses, RHCV and HHCV respectively, are formed after the inoculation of genomic DNA in Madin-Darby bovine kidney cell line cultures. RHCV is closely related to the HCV-1a/HCV-1b genotypes and HHCV is more closely related to the HCV-1b genotype. These findings could contribute to the understanding of HCV origin as well as clarify the virus life cycle, pathogenesis, evolution and diversity.
Forebrain microglia from wild-type but not adult 5xFAD mice prevent amyloid-β plaque formation in organotypic hippocampal slice cultures
Authors: Hellwig Sabine , Masuch Annette , Nestel Sigrun , Katzmarski Natalie , Meyer-Luehmann Melanie , Biber Knut 
Published: September 2015

AbstractThe role of microglia in amyloid-β (Aβ) deposition is controversial. In the present study, an organotypic hippocampal slice culture (OHSC) system with an in vivo-like microglial-neuronal environment was used to investigate the potential contribution of microglia to Aβ plaque formation. We found that microglia ingested Aβ, thereby preventing plaque formation in OHSCs. Conversely, Aβ deposits formed rapidly in microglia-free wild-type slices. The capacity to prevent Aβ plaque formation was absent in forebrain microglia from young adult but not juvenile 5xFamilial Alzheimer’s disease (FAD) mice. Since no loss of Aβ clearance capacity was observed in both wild-type and cerebellar microglia from 5xFAD animals, the high Aβ1−42 burden in the forebrain of 5xFAD animals likely underlies the exhaustion of microglial Aβ clearance capacity. These data may therefore explain why Aβ plaque formation has never been described in wild-type mice and point to a beneficial role of microglia in AD pathology. We also describe a new method to study Aβ plaque formation in a cell culture setting.
Orbital pacing of carbon fluxes by a ∼9-My eccentricity cycle during the Mesozoic
Authors: Martinez Mathieu , Dera Guillaume 
Published: September 2015

Significance
The Milankovitch cycles are orbitally paced variations in insolation that drove periodic climate changes on Earth at the scale of tens to hundreds of thousands years. Longer ‟grand orbital cycles” also exist, but their impacts on paleoclimate dynamics are not well documented for pre-Cenozoic times. Here we tackle this issue by analyzing the stable isotope fluctuations recorded by fossil cephalopods throughout the Jurassic–Early Cretaceous interval. We document a periodicity of ∼9 My in the carbon cycle, except from 190 to 180 Ma when disturbances occurred. This orbital forcing affected carbon transfers by modulating the hydrological processes and sea-level changes. In summary, this ∼9-My orbital cycle is an important metronome of the greenhouse climate dynamics.
Genetic specificity of face recognition
Authors: Shakeshaft Nicholas G. , Plomin Robert 
Published: September 2015

Significance
Diverse cognitive abilities have typically been found to intercorrelate highly and to be strongly influenced by genetics. Recent twin studies have suggested that the ability to recognize human faces is an exception: it is similarly highly heritable, but largely uncorrelated with other abilities. However, assessing genetic relationships—the degree to which traits are influenced by the same genes—requires very large samples, which have not previously been available. This study, using data from more than 2,000 twins, shows for the first time, to our knowledge, that the genetic influences on face recognition are almost entirely unique. This finding provides strong support for the view that face recognition is “special” and may ultimately illuminate the nature of cognitive abilities in general.
Enhanced precipitation variability decreases grass- and increases shrub-productivity
Authors: Gherardi Laureano A. , Sala Osvaldo E. 
Published: September 2015

Significance
Although increased climatic variability resulting from climate change has been accepted by the scientific community and forms part of the public narrative, studies of the effect of climatic variability on ecosystems have received much less attention than effects of changes in the mean state of climate. Here, we report on a field experiment where we experimentally increased interannual variability of precipitation while maintaining average precipitation constant. Our results indicated that total productivity and that of grasses declined in response to increased precipitation variability, although shrubs benefited, suggesting a potential shift from grassland to shrubland in the future, with large consequences for the supply of ecosystem services. In addition, the effect of variability increased through time.
Mathematical framework for activity-based cancer biomarkers
Authors: Kwong Gabriel A. , Dudani Jaideep S. , Carrodeguas Emmanuel , Mazumdar Eric V. , Zekavat Seyedeh M. , Bhatia Sangeeta N. 
Published: September 2015

Significance
The discovery of cancer at an early stage improves treatment outcomes, yet cancer detection thresholds based on measuring the abundance of biomarkers produced by small tumors are biologically limited. Here we develop a mathematical framework to explore the use of activity-based biomarkers for early cancer detection. In contrast to abundance-based biomarkers, activity-based biomarkers rely on the catalytic activity of enzymes to amplify cancer-derived signals and allow detection of small tumors. Using a class of activity-based biomarkers called synthetic biomarkers, we comprehensively explore how detection sensitivities depend on probe design, enzymatic activity, and organ physiology, and how they may be precisely tuned to reveal the presence of small tumors in humans.
Stress impairs cognitive flexibility in infants
Authors: Seehagen Sabine , Schneider Silvia , Rudolph Julia , Ernst Stephanie , Zmyj Norbert 
Published: September 2015

Significance
Infancy is regarded as a period of increased vulnerability to stress, but it is currently unknown how stress influences cognitive functioning in infants. Studies with adults have revealed that stress promotes rigid habitual behavior at the cost of flexible behavior. Here we show that stress similarly affects 15-mo-old infants. Half of the infants underwent a stress induction, the other half did not. Then, all infants learned to habitually perform an action that produced an interesting effect. Once the action had become ineffective, only stressed infants continued performing this action, showing rigid habitual behavior. Nonstressed infants explored an alternative action, showing flexible behavior. If stress occurs frequently, infants’ failure to explore alternative behaviors could hamper knowledge acquisition in the long term.
Glycan modulation and sulfoengineering of anti–HIV-1 monoclonal antibody PG9 in plants
Authors: Loos Andreas , Gach Johannes S. , Hackl Thomas , Maresch Daniel , Henkel Theresa , Porodko Andreas , Bui-Minh Duc , Sommeregger Wolfgang , Wozniak-Knopp Gordana , Forthal Donald N. , Altmann Friedrich , Steinkellner Herta , Mach Lukas 
Published: September 2015

SignificanceThe broadly neutralizing anti–HIV-1 monoclonal antibody (mAb) PG9 requires multiple posttranslational modifications to exhibit its full biological activity, including properN-glycosylation and tyrosine sulfation. We now describe a technology that permits the controlled synthesis of these modifications inNicotiana benthamiana. This technology allowed us to show that sulfated PG9 neutralizes HIV-1 with much higher potency than unsulfated antibody. We also found that glycooptimized mAb versions made in plants are superior to PG9 produced in mammalian cells with respect to mediating antibody-dependent cellular cytotoxicity, an important mAb effector function. Because effector functions are of key importance for antibody-mediated immune control of HIV-1 infections, our results can instruct the development of improved immunotherapeutics for the treatment of AIDS patients.
Motifs of VDAC2 required for mitochondrial Bak import and tBid-induced apoptosis
Authors: Naghdi Shamim , Várnai Péter , Hajnóczky György 
Published: September 2015

Significance
Voltage-dependent anion channel 2 (VDAC2), like other VDAC proteins, transports solutes across the outer mitochondrial membrane, but it is the only isoform that supports mitochondrial import of cell death-executing proteins, Bak/Bax. To address the underlying mechanism, we created chimeras of VDAC2 and VDAC1 and tested their competency to rescue Bak insertion and apoptosis in VDAC2-deficient cells. Our gain-of-function studies revealed that the middle domain (123–179 aa) is required for rescue. Loss-of-function studies identified two critical residues (T168, D170). Finally, applying these clues to recently solved structures we identified a discrete site on the cytoplasmic side of VDAC2's pore that likely supports Bak insertion and apoptosis.
Extent of hippocampal atrophy predicts degree of deficit in recall
Authors: Patai Eva Zita , Gadian David G. , Cooper Janine M. , Dzieciol Anna M. , Mishkin Mortimer , Vargha-Khadem Faraneh 
Published: September 2015

Significance
Which memory processes are dependent on the hippocampus is still being debated. Using data obtained from a large cohort of patients who had sustained hippocampal damage early in life enabled us to determine which type of mnemonic deficit showed a correlation with extent of hippocampal injury. Scores on tests of recall memory correlated significantly with hippocampal volumes, but scores on equally difficult tests of recognition memory did not. The results provide strong support for the view that the hippocampus is essential for recall but not for recognition.
Mechanisms of leiomodin 2-mediated regulation of actin filament in muscle cells
Authors: Chen Xiaorui , Ni Fengyun , Kondrashkina Elena , Ma Jianpeng , Wang Qinghua 
Published: September 2015

Significance
Actin filaments are the fundamental building blocks for cellular motility in muscle cells. However, the regulation of actin filaments in sarcomeres is poorly understood. Lmod is a class of potent tandem-G-actin–binding nucleators in muscle cells. Lmod mutations, deletion, or instability lead to lethal nemaline myopathy. Here we report the crystal structure of actin–Lmod2 complex and complementary functional studies. Our data collectively unraveled the mechanisms of Lmod’s essential functions as an actin nucleator and filament length regulator, thus providing a solid foundation for understanding the molecular basis of disease-causing mutations and malfunctions of Lmod that often are life threatening. Most importantly, our results suggest a previously unrecognized level of regulation in mammalian signal transduction mediated by certain tandem-G-actin–binding nucleators.
Minimal model for collective kinetochore–microtubule dynamics
Authors: Banigan Edward J. , Chiou Kevin K. , Ballister Edward R. , Mayo Alyssa M. , Lampson Michael A. , Liu Andrea J. 
Published: September 2015

Significance
Coordinated metaphase chromosome motions are driven by microtubule (MT) dynamics. MTs stochastically switch between growing and shrinking states with rates that depend on forces and biochemical factors acting at the kinetochore–MT interface. Single-MT behavior is known from in vitro experiments, but it is unclear how many MTs cooperate to control chromosome dynamics. We construct and experimentally test a minimal model for collective MT dynamics. The force dependence of the MTs leads to bistable and hysteretic dynamics. This produces chromosome oscillations and error-correcting behavior, as observed in vivo. Our model provides a mechanistic, predictive framework in which we can incorporate further biological complexity.