bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure and Function of Cyanobacterial DHDPS and DHDPR
Authors: Christensen Janni B. , Soares da Costa T. P. , Faou Pierre , Pearce F. Grant , Panjikar Santosh , Perugini Matthew A. 
Published: November 2016

AbstractLysine biosynthesis in bacteria and plants commences with a condensation reaction catalysed by dihydrodipicolinate synthase (DHDPS) followed by a reduction reaction catalysed by dihydrodipicolinate reductase (DHDPR). Interestingly, both DHDPS and DHDPR exist as different oligomeric forms in bacteria and plants. DHDPS is primarily a homotetramer in all species, but the architecture of the tetramer differs across kingdoms. DHDPR also exists as a tetramer in bacteria, but has recently been reported to be dimeric in plants. This study aimed to characterise for the first time the structure and function of DHDPS and DHDPR from cyanobacteria, which is an evolutionary important phylum that evolved at the divergence point between bacteria and plants. We cloned, expressed and purified DHDPS and DHDPR from the cyanobacterium Anabaena variabilis. The recombinant enzymes were shown to be folded by circular dichroism spectroscopy, enzymatically active employing the quantitative DHDPS-DHDPR coupled assay, and form tetramers in solution using analytical ultracentrifugation. Crystal structures of DHDPS and DHDPR from A. variabilis were determined at 1.92 Å and 2.83 Å, respectively, and show that both enzymes adopt the canonical bacterial tetrameric architecture. These studies indicate that the quaternary structure of bacterial and plant DHDPS and DHDPR diverged after cyanobacteria evolved.
Serotonergic Modulation Differentially Targets Distinct Network Elements within the Antennal Lobe of Drosophila melanogaster
Authors: Sizemore Tyler R. , Dacks Andrew M. 
Published: November 2016

AbstractNeuromodulation confers flexibility to anatomically-restricted neural networks so that animals are able to properly respond to complex internal and external demands. However, determining the mechanisms underlying neuromodulation is challenging without knowledge of the functional class and spatial organization of neurons that express individual neuromodulatory receptors. Here, we describe the number and functional identities of neurons in the antennal lobe of Drosophila melanogaster that express each of the receptors for one such neuromodulator, serotonin (5-HT). Although 5-HT enhances odor-evoked responses of antennal lobe projection neurons (PNs) and local interneurons (LNs), the receptor basis for this enhancement is unknown. We used endogenous reporters of transcription and translation for each of the five 5-HT receptors (5-HTRs) to identify neurons, based on cell class and transmitter content, that express each receptor. We find that specific receptor types are expressed by distinct combinations of functional neuronal classes. For instance, the excitatory PNs express the excitatory 5-HTRs, while distinct classes of LNs each express different 5-HTRs. This study therefore provides a detailed atlas of 5-HT receptor expression within a well-characterized neural network, and enables future dissection of the role of serotonergic modulation of olfactory processing.
Psychiatric and neurological disorders are associated with bullous pemphigoid – a nationwide Finnish Care Register study
Authors: Försti Anna-Kaisa , Jokelainen Jari , Ansakorpi Hanna , Seppänen Allan , Majamaa Kari , Timonen Markku , Tasanen Kaisa 
Published: November 2016

AbstractBullous pemphigoid (BP) is an autoimmune blistering skin disease with increasing incidence. BP is associated with neurological disorders, but it has not been established, what subtypes of dementia and stroke are associated with BP, and what is the temporal relation between these diseases. Also, the association between BP and psychiatric disorders is controversial. We conducted a retrospective nationwide study, using the Finnish Care Register for Health Care diagnoses between 1987 and 2013. The study population of 4524 BP patients were compared with 66138 patients with basocellular carcinoma (BCC), neurological and psychiatric comorbid disorders were evaluated for both groups, and associations were estimated by Cox regression and logistic regression analyses. The strongest risk of developing BP was found after diagnosis of multiple sclerosis (MS) (OR=5.9, 95% CI 3.9–8.5). Among psychiatric diseases, the corresponding risk was strongest in schizophrenia (OR=2.7, 95% CI 2.0–3.5), and as a novel finding, also personality disorders (OR=2.2, 95% CI 1.3–3.3) preceded BP. In conclusion, many psychiatric disorders, especially schizophrenia, carry heightened risk for BP. Furthermore, several neurological diseases which cause central nervous system inflammation or degeneration were related to BP, and the association was strongest between MS and BP.
Regulating Mid-infrared to Visible Fluorescence in Monodispersed Er3+-doped La2O2S (La2O2SO4) Nanocrystals by Phase Modulation
Authors: Pan Qiwen , Yang Dandan , Kang Shiliang , Qiu Jianrong , Dong Guoping 
Published: November 2016

AbstractRare earth doped mid-infrared (MIR) fluorescent sources have been widely investigated due to their various potential applications in the fields of communication, chemical detecting, medical surgery and so forth. However, with emission wavelength extended to MIR, multiphonon relaxation process that strongly quenched the MIR emission is one of the greatest challenges for such practical applications. In our design, we have described a controllable gas-aided annealing strategy to modulate the phase, crystal size, morphology and fluorescent performance of a material simultaneously. Uniform and monodispersed Er3+-doped La2O2S and La2O2SO4 nanocrystals with a similar lattice structure, crystallinity, diameter and morphology have been introduced to investigate the impact of multiphonon relaxation on luminescence performance. Detailed spectroscopic evolutions in the region of MIR, near-infrared (NIR), visible upconversion (UC) and their corresponding decay times provide insight investigation into the fluorescent mechanism caused by multiphonon relaxation. A possible energy transfer model has also been established. Our results present direct observation and mechanistic investigation of fluorescent evolution in multiphonon relaxation process, which is conductive to design MIR fluorescent materials in the future. To the best of our knowledge, it is the first investigation on MIR fluorescent performance of La2O2S nanocrystals, which may find various applications in many photoelectronic fields.
MicroRNA-124 promotes hepatic triglyceride accumulation through targeting tribbles homolog 3
Authors: Liu Xing , Zhao Jiejie , Liu Qi , Xiong Xuelian , Zhang Zhijian , Jiao Yang , Li Xiaoying , Liu Bin , Li Yao , Lu Yan 
Published: November 2016

AbstractAn increase in hepatic triglyceride (TG) contents usually results in non-alcoholic fatty liver disease (NAFLD) and related metabolic diseases. However, the mechanisms underlying perturbations of hepatic TG homeostasis remain largely unknown. Here, we showed that MicroRNA-124 was up-regulated in the livers of C57BL/6 mice fed a short-term high-fat-diet (HFD). Adenoviral overexpression of miR-124 in C57BL/6 mice led to accumulation of excessive triglycerides and up-regulation of lipogenic genes in the liver. We further identified tribbles homolog 3 (TRB3) as a direct target of miR-124. AKT signaling, which is negatively regulated by TRB3, was enhanced by miR-124 overexpression. Moreover, restoration of TRB3 expression markedly abolished the effect of miR-124 on hepatic TG metabolism. Therefore, our findings revealed that miR-124 played a role in mediating high-fat-diet induced TG accumulation in the liver.
A comparative analysis and guidance for individualized chemotherapy of stage II and III colorectal cancer patients based on pathological markers
Authors: Han Yang , Lu Su , Yu Fudong , Liu Xisheng , Sun Huimin , Wang Jingtao , Zhu Xingwu , Lu Huijun , Yue Hao , Wang Jing , Lin Jun , Zhou Chongzhi , Tang Huamei , Peng Zhihai 
Published: November 2016

AbstractAdjuvant chemotherapy is considered the standard of care for patients with colorectal cancer after curative resection. Although current guidelines provide clear instructions for chemotherapy for stage II high-risk and stage III colorectal cancer, it is insufficient to individualize therapy. We analyzed the outcomes of 902 patients with colorectal cancer treated with or without chemotherapy in our hospital. We found Chinese survival benefit for chemotherapy was consistent with current guidelines. Moreover, our data added to the evidence that chemotherapy might be used for elderly patients with stage II high-risk colorectal cancer. Pathological markers could predict response to individualize therapy in a convenient, fast and inexpensive way. We compared survivals of patients with stage II high-risk and stage III colorectal cancer with chemotherapy in different pathological markers expression, and furthermore used 458 colon adenocarcinoma samples from The Cancer Genome Atlas to verify our preliminary results. We confirmed TOPIIα, EGFR and P170 may be sufficiently predictive markers to individualize chemotherapy. FOLFOX was the optimal adjuvant chemotherapy for patients with stage II high-risk and stage III colorectal cancer when TOPIIα was positive or EGFR or P170 was negative.
Vibrational resonance, allostery, and activation in rhodopsin-like G protein-coupled receptors
Authors: Woods Kristina N. , Pfeffer Jürgen , Dutta Arpana , Klein-Seetharaman Judith 
Published: November 2016

AbstractG protein-coupled receptors are a large family of membrane proteins activated by a variety of structurally diverse ligands making them highly adaptable signaling molecules. Despite recent advances in the structural biology of this protein family, the mechanism by which ligands induce allosteric changes in protein structure and dynamics for its signaling function remains a mystery. Here, we propose the use of terahertz spectroscopy combined with molecular dynamics simulation and protein evolutionary network modeling to address the mechanism of activation by directly probing the concerted fluctuations of retinal ligand and transmembrane helices in rhodopsin. This approach allows us to examine the role of conformational heterogeneity in the selection and stabilization of specific signaling pathways in the photo-activation of the receptor. We demonstrate that ligand-induced shifts in the conformational equilibrium prompt vibrational resonances in the protein structure that link the dynamics of conserved interactions with fluctuations of the active-state ligand. The connection of vibrational modes creates an allosteric association of coupled fluctuations that forms a coherent signaling pathway from the receptor ligand-binding pocket to the G-protein activation region. Our evolutionary analysis of rhodopsin-like GPCRs suggest that specific allosteric sites play a pivotal role in activating structural fluctuations that allosterically modulate functional signals.
A targeted proteomic multiplex CSF assay identifies increased malate dehydrogenase and other neurodegenerative biomarkers in individuals with Alzheimer’s disease pathology
Authors: Paterson R W , Heywood W E , Heslegrave A J , Magdalinou N K , Andreasson U , Sirka E , Bliss E , Slattery C F , Toombs J , Svensson J , Johansson P , Fox N C , Zetterberg H , Mills K , Schott J M 
Published: November 2016

AbstractAlzheimer’s disease (AD) is the most common cause of dementia. Biomarkers are required to identify individuals in the preclinical phase, explain phenotypic diversity, measure progression and estimate prognosis. The development of assays to validate candidate biomarkers is costly and time-consuming. Targeted proteomics is an attractive means of quantifying novel proteins in cerebrospinal and other fluids, and has potential to help overcome this bottleneck in biomarker development. We used a previously validated multiplexed 10-min, targeted proteomic assay to assess 54 candidate cerebrospinal fluid (CSF) biomarkers in two independent cohorts comprising individuals with neurodegenerative dementias and healthy controls. Individuals were classified as ‘AD’ or ‘non-AD’ on the basis of their CSF T-tau and amyloid Aβ1–42 profile measured using enzyme-linked immunosorbent assay; biomarkers of interest were compared using univariate and multivariate analyses. In all, 35/31 individuals in Cohort 1 and 46/36 in Cohort 2 fulfilled criteria for AD/non-AD profile CSF, respectively. After adjustment for multiple comparisons, five proteins were elevated significantly in AD CSF compared with non-AD CSF in both cohorts: malate dehydrogenase; total APOE; chitinase-3-like protein 1 (YKL-40); osteopontin and cystatin C. In an independent multivariate orthogonal projection to latent structures discriminant analysis (OPLS-DA), these proteins were also identified as major contributors to the separation between AD and non-AD in both cohorts. Independent of CSF Aβ1–42 and tau, a combination of these biomarkers differentiated AD and non-AD with an area under curve (AUC)=0.88. This targeted proteomic multiple reaction monitoring (MRM)-based assay can simultaneously and rapidly measure multiple candidate CSF biomarkers. Applying this technique to AD we demonstrate differences in proteins involved in glucose metabolism and neuroinflammation that collectively have potential clinical diagnostic utility.
Dual CDS scheme embedded in SAR‐based ADCs for low‐noise CMOS imagers without a PGA
Authors: Kim M.‐K. , Hong S.‐K. , Gou J. , Kwon O.‐K. 
Published: November 2016

A dual correlated double sampling (CDS) scheme, which can be embedded into a successive approximation register (SAR) or SAR/single‐slope analogue‐to‐digital converters (ADCs) for low‐noise CMOS imagers without the use of a power‐consuming programmable gain amplifier (PGA) is proposed. To reduce the noise of the readout channel, the proposed dual CDS scheme removes the sampling error, which occurs in the capacitor digital‐to‐analogue converter (DAC), by storing only a reset voltage of the pixel into the capacitor DAC. In addition, without using the PGA, it amplifies the output of the readout channel by controlling the reference voltages of the ADC. The readout channel using the proposed CDS scheme was designed using a 90 nm CMOS imager process technology. The simulation results show that the signal‐to‐noise‐distortion ratio of the readout channel using the proposed dual CDS scheme is 81.8 dB, which is an improvement of 10.8 dB over the digital CDS scheme. In addition, the output of the readout channel is amplified without the use of a PGA.
Global patterns of kelp forest change over the past half-century
Authors: Krumhansl Kira A. , Okamoto Daniel K. , Rassweiler Andrew , Novak Mark , Bolton John J. , Cavanaugh Kyle C. , Connell Sean D. , Johnson Craig R. , Konar Brenda , Ling Scott D. , Micheli Fiorenza , Norderhaug Kjell M. , Pérez-Matus Alejandro , Sousa-Pinto Isabel , Reed Daniel C. , Salomon Anne K. , Shears Nick T. , Wernberg Thomas , Anderson Robert J. , Barrett Nevell S. , Buschmann Alejandro H. , Carr Mark H. , Caselle Jennifer E. , Derrien-Courtel Sandrine , Edgar Graham J. , Edwards Matt , Estes James A. , Goodwin Claire , Kenner Michael C. , Kushner David J. , Moy Frithjof E. , Nunn Julia , Steneck Robert S. , Vásquez Julio , Watson Jane , Witman Jon D. , Byrnes Jarrett E. K. 
Published: November 2016

Significance
Kelp forests support diverse and productive ecological communities throughout temperate and arctic regions worldwide, providing numerous ecosystem services to humans. Literature suggests that kelp forests are increasingly threatened by a variety of human impacts, including climate change, overfishing, and direct harvest. We provide the first globally comprehensive analysis of kelp forest change over the past 50 y, identifying a high degree of variation in the magnitude and direction of change across the geographic range of kelps. These results suggest region-specific responses to global change, with local drivers playing an important role in driving patterns of kelp abundance. Increased monitoring aimed at understanding regional kelp forest dynamics is likely to prove most effective for the adaptive management of these important ecosystems.
Socioecological transitions trigger fire regime shifts and modulate fire–climate interactions in the Sierra Nevada, USA, 1600–2015 CE
Authors: Taylor Alan H. , Trouet Valerie , Skinner Carl N. , Stephens Scott 
Published: November 2016

SignificanceTwenty-first–century climate change is projected to increase fire activity in California, but predictions are uncertain because humans can amplify or buffer fire–climate relationships. We combined a tree-ring–based fire history with 20th-century area burned data to show that large fire regime shifts during the past 415 y corresponded with socioecological change, and not climate variability. Climate amplified large-scale fire activity after Native American depopulation reduced the buffering effect of Native American burns on fire spread. Later Euro-American settlement and fire suppression buffered fire activity from long-term temperature increases. Our findings highlight a need to enhance our understanding of human–fire interactions to improve the skill of future projections of fire driven by climate change.
Long-term empirical evidence of ocean warming leading to tropicalization of fish communities, increased herbivory, and loss of kelp
Authors: Vergés Adriana , Doropoulos Christopher , Malcolm Hamish A. , Skye Mathew , Garcia-Pizá Marina , Marzinelli Ezequiel M. , Campbell Alexandra H. , Ballesteros Enric , Hoey Andrew S. , Vila-Concejo Ana , Bozec Yves-Marie , Steinberg Peter D. 
Published: November 2016

Significance
Most studies of the impact of global warming focus on the direct physiological impacts of climate change. However, global warming is shifting the distribution of many species and leading to novel interactions between previously separated species that have the potential to transform entire ecological communities. This study shows that an increase in the proportion of warmwater species (“tropicalization”) as oceans warm is increasing fish herbivory in kelp forests, contributing to their decline and subsequent persistence in alternate “kelp-free” states. These tropical and subtropical herbivores are increasingly impacting temperate algal communities worldwide, posing a significant threat to the long-term stability of these iconic ecosystems and the valuable services they provide.
Synergistic reaction of silver nitrate, silver nanoparticles, and methylene blue against bacteria
Authors: Li Runze , Chen Jie , Cesario Thomas C. , Wang Xin , Yuan Joshua S. , Rentzepis Peter M. 
Published: November 2016

Significance
Bacteria are increasingly becoming resistant to antibiotics; therefore, other means must be found for their inactivation. Efficient inactivation of bacteria cannot be achieved simply by increasing the dose because of toxicity limitation. Therefore, it is critical to search for a combination of agents, within a safe dose, that is more effective in killing bacteria than agents reacting alone. Here, we show that the combination of methylene blue (MB) and silver nitrate can be up to three orders of magnitude more effective in killing bacteria than the two agents reacting alone against bacteria. This synergistic mechanism is due to silver ion increasing the penetration of MB into the bacteria interior, allowing photogenerated single oxygen to react with DNA and prevent replication.
Notch1 controls development of the extravillous trophoblast lineage in the human placenta
Authors: Haider Sandra , Meinhardt Gudrun , Saleh Leila , Fiala Christian , Pollheimer Jürgen , Knöfler Martin 
Published: November 2016

SignificanceProgenitor trophoblast cells of the human placenta either fuse to form a syncytium or develop into invasive trophoblasts invading the maternal uterus. However, regulatory pathways controlling their development and distinct differentiation programs are poorly understood. In the present study, we demonstrate that Notch1 is a critical regulator of early pregnancy, promoting development of the invasive, extravillous trophoblast lineage and survival of its progenitors. In vivo, Notch1 is detected in extravillous trophoblast progenitors and clusters of villous trophoblast initiating the invasive differentiation program. In vitro, Notch1 repressed genes involved in self-renewal of fusogenic precursors, but induced genes specifically expressed by extravillous trophoblast progenitors. Our data delineate Notch1 as a key regulator promoting development of the human extravillous trophoblast lineage.
Nanoparticle engineered TRAIL-overexpressing adipose-derived stem cells target and eradicate glioblastoma via intracranial delivery
Authors: Jiang Xinyi , Fitch Sergio , Wang Christine , Wilson Christy , Li Jianfeng , Grant Gerald A. , Yang Fan 
Published: November 2016

Significance
Current treatment for glioblastoma multiforme (GBM) fails to address its highly infiltrative nature; treatment often leaves behind microscopic neoplastic satellites, resulting in eventual tumor recurrence. Here we report polymeric nanoparticle-engineered human adipose-derived stem cells (hADSCs) overexpressing the cancer-specific TNF-related apoptosis-inducing ligand for targeting and eradicating glioblastoma cells. Engineered hADSCs exhibited long-range directional migration toward tumor in patient-derived GBM orthotropic xenografts and showed significant inhibition of tumor growth and extension of animal survival. Repetitive injection further prolonged animal survival compared with single injection. Together, our data suggest that nanoparticle-engineered hADSCs exhibit the therapeutically relevant behavior of “seek-and-destroy” tumortropic migration, and may offer a promising therapy for substantial enhancement of GBM treatment.
Relationship Between Cesarean Delivery Rate and Maternal and Neonatal Mortality
Authors: Molina George , Weiser Thomas G. , Lipsitz Stuart R. , Esquivel Micaela M. , Uribe-Leitz Tarsicio , Azad Tej , Shah Neel , Semrau Katherine , Berry William R. , Gawande Atul A. , Haynes Alex B. 
Published: November 2016

(JAMA 2015;314(21):2263–2270)
Cesarean deliveries can be lifesaving for women with obstructed labor and other emergency conditions. As per the World Health Organization (WHO) recommendation, cesarean delivery rates should not exceed 10% to 15% of deliveries. However, actual rates are higher in many countries. The aim of this study was to provide better estimates of the contemporary relationship between national cesarean delivery rates and neonatal and maternal mortality.
Pharmacokinetics and Pharmacodynamics of Drugs Commonly Used in Pregnancy and Parturition
Authors: Ansari Jessica , Carvalho Breandan , Shafer Steven L. , Flood Pamela 
Published: November 2016

(Anesth Analg 2016;122:786–804)
There is a lack of pharmacokinetic and pharmacodynamic studies in parturients. In addition, while current regulations require such studies to be conducted in women of childbearing potential, very few medications have been studied in the setting of pregnancy, with most drugs being used off-label. As such, there are inadequate data for physicians and patients to make informed decisions regarding drug use during pregnancy and lactation. In this review, the authors discussed known alterations in drug pharmacokinetics and pharmacodynamics that occur during pregnancy as well as the impact of acute changes in physiology during childbirth.