bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenosine A2A receptor inactivation alleviates early-onset cognitive dysfunction after traumatic brain injury involving an inhibition of tau hyperphosphorylation
Authors: Zhao Z-A , Zhao Y , Ning Y-L , Yang N , Peng Y , Li P , Chen X-Y , Liu D , Wang H , Chen X , Bai W , Chen J-F , Zhou Y-G 
Published: May 2017

AbstractTau is a microtubule-associated protein, and the oligomeric and hyperphosphorylated forms of tau are increased significantly after neurotrauma and considered important factors in mediating cognitive dysfunction. Blockade of adenosine A2A receptors, either by caffeine or gene knockout (KO), alleviates cognitive dysfunction after traumatic brain injury (TBI). We postulated that A2AR activation exacerbates cognitive impairment via promoting tau hyperphosphorylation. Using a mouse model of moderate controlled cortical impact, we showed that TBI induced hyperphosphorylated tau (p-tau) in the hippocampal dentate gyrus and spatial memory deficiency in the Morris water maze test at 7 days and 4 weeks after TBI. Importantly, pharmacological blockade (A2AR antagonist ZM241385 or non-selective adenosine receptor antagonist caffeine) or genetic inactivation of A2ARs reduced the level of tau phosphorylation at Ser404 and alleviated spatial memory dysfunction. The A2AR control of p-tau is further supported by the observations that a KO of A2AR decreased the activity of the tau phosphorylation kinases, glycogen synthase kinase-3β (GSK-3β) and protein kinase A (PKA) after TBI, and by that CGS21680 (A2AR agonist) exacerbated okadaic acid-induced tau hyperphosphorylation in cultured primary hippocampal neurons. Lastly, CGS21680-induced neuronal tau hyperphosphorylation and axonal injury were effectively alleviated by individual treatments with ZM241385 (A2AR antagonist), H89 (PKA antagonist) and SB216763 (GSK-3β antagonist), or by the combined treatment with H89 and SB216763. Our findings suggest a novel mechanism whereby A2AR activation triggers cognitive dysfunction by increasing the phosphorylation level of tau protein after TBI and suggest a promising therapeutic and prophylactic strategy by targeting aberrant A2AR signaling via tau phosphorylation.
Miniaturised highly selective bandpass filter with very wide stopband using meander coupled lines
Authors: Killamsetty V.K. , Mukherjee B. 
Published: May 2017

A compact wideband bandpass filter with a very wide stopband for terrestrial radio (TETRA) band applications is proposed. The proposed filter employs two types of resonators: one is tri‐section half wavelength stepped impedance resonator (SIR) and the other is stub‐loaded shorted ring resonator. The proposed filter has adopted SIRs and meandering technique in achieving miniaturised size. Spur‐lines and tapped feeding techniques are infused in the filter to suppress harmonics so as to achieve wide stopband. Cross‐coupling is introduced in the filter for acquiring good selectivity. This highly selective filter has a miniaturised size of 0.09 × 0.12λg (28 × 36.8 mm2) with a wide stopband up to 8.75f0 (f0 is the centre frequency of filter) with 25 dB harmonics suppression level.
Comparison of the Effects of Mitiglinide and Glibenclamide Administered in Combination with the Dipeptidyl Peptidase-IV Inhibitor Sitagliptin in Rats with Streptozotocin-Nicotinamide-Induced Type 2 Diabetes
Authors: Akahane Kenji , Ojima Kazuma , Yokoyama Ayaka , Inoue Toshihiro , Kiguchi Sumiyoshi , Tatemichi Satoshi , Takeda Hiroo , Kobayashi Mamoru 
Published: May 2017

Abstract
We compared the individual effects of mitiglinide and glibenclamide administered in combination with the dipeptidyl peptidase-IV (DPP-IV) inhibitor sitagliptin on plasma DPP-IV activity and blood glucose levels in rats with streptozotocin-nicotinamide-induced type 2 diabetes (STZ-NA rats).
We examined the inhibitory activity of mitiglinide and glibenclamide as well as their combination with sitagliptin on plasma DPP-IV activity in STZ-NA rats. The oral glucose tolerance test (OGTT) was used to compare effects of mitiglinide, glibenclamide, and their combination with sitagliptin on blood glucose levels in STZ-NA rats.
Mitiglinide and glibenclamide did not inhibit rat DPP-IV and did not influence the inhibitory effect of sitagliptin on rat plasma DPP-IV activity. In STZ-NA rats, plasma glucose levels were stronger suppressed by a combination of mitiglinide and sitagliptin than by either drug used alone. However, no clear effect of the combination of glibenclamide and sitagliptin was observed.
These results indicate that the combination of mitiglinide and sitagliptin has a lower risk of hypoglycemia in the rats with induced type 2 diabetes compared with the combination of glibenclamide and sitagliptin. The combination of mitiglinide and sitagliptin can be a promising combination for the treatment of diabetic patients.
Klassifikation, Genetik und Epidemiologie der Glaukome
Authors: Höhn René , Pfeiffer Norbert 
Published: May 2017

ZusammenfassungDie Glaukome bilden eine sehr heterogene Krankheitsgruppe, der ein retinaler Ganglienzellverlust mit typischer Papillenexkavation und charakteristischen Gesichtsfeldausfällen gemeinsam ist. Glaukome sind der häufigste Grund für eine irreversible Erblindung weltweit. Dieser Beitrag gibt einen aktuellen Überblick über die Einteilung und die genetischen Grundlagen der Glaukome.
Die randunscharfe Papille: eine diagnostische Herausforderung
Authors: Biermann Julia , Lagrèze Wolf 
Published: May 2017

ZusammenfassungDie Differenzialdiagnosen bei Papillenrandunschärfe sind zahlreich. Harmlose Ursachen und Normvarianten müssen von pathologischen Ursachen abgegrenzt werden. Die Papillenschwellung und insbesondere die Stauungspapille erfordern zeitnah weitere Diagnostik und Therapie.
From Pharmacognosia to DNA-Based Medicinal Plant Authentication – Pharmacognosy through the Centuries
Authors: Heinrich Michael , Anagnostou Sabine 
Published: May 2017

AbstractFor centuries, pharmacognosy was essential for the identification, quality, purity, and, until the end of the 18th century, even for the efficacy of medicinal plants. Since the 19th century, it concentrated on authenticity, purity, quality and the analysis of active substances, and was established as an academic branch discipline within pharmacy and continuously developed into a modern, highly sophisticated science. Even though the paradigm in pharmacy changed in the 19th century with the discovery of morphine and concentrated on single substances that could be synthesized fast by the upcoming industry, medicinal plants always remained an important element of the Materia medica, and during the last decades, medicinal plants continue to be a source of remedies, and natural products are an inspiration for new medicine. In this research, pharmacognostic skills remain an essential element, both with regards to identity, quality assurance of botanicals (both herbal medicines and supplements), and the discovery and development of new medicines. Over the years, the specific pharmacognostical tools have changed dramatically, and most recently, DNA-based techniques have become another element of our spectrum of scientific methods.
Production of the Cytotoxic Cardenolide Glucoevatromonoside by Semisynthesis and Biotransformation of Evatromonoside by a Digitalis lanata Cell Culture
Authors: Munkert Jennifer , Santiago Franco Marina , Nolte Elke , Thaís Silva Izabella , Oliveira Castilho Rachel , Melo Ottoni Flaviano , Schneider Naira , Oliveira Mônica , Taubert Helge , Bauer Walter , Andrade Saulo , Alves Ricardo , Simões Cláudia , Braga Fernão , Kreis Wolfgang , de Pádua Rodrigo 
Published: May 2017

AbstractRecent studies demonstrate that cardiac glycosides, known to inhibit Na+/K+-ATPase in humans, have increased susceptibility to cancer cells that can be used in tumor therapy. One of the most promising candidates identified so far is glucoevatromonoside, which can be isolated from the endangered species Digitalis mariana ssp. heywoodii. Due to its complex structure, glucoevatromonoside cannot be obtained economically by total chemical synthesis. Here we describe two methods for glucoevatromonoside production, both using evatromonoside obtained by chemical degradation of digitoxin as the precursor. 1) Catalyst-controlled, regioselective glycosylation of evatromonoside to glucoevatromonoside using 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide as the sugar donor and 2-aminoethyldiphenylborinate as the catalyst resulted in an overall 30 % yield. 2) Biotransformation of evatromonoside using Digitalis lanata plant cell suspension cultures was less efficient and resulted only in overall 18 % pure product. Structural proof of products has been provided by extensive NMR data. Glucoevatromonoside and its non-natural 1–3 linked isomer neo-glucoevatromonoside obtained by semisynthesis were evaluated against renal cell carcinoma and prostate cancer cell lines.
Polyketide mimetics yield structural and mechanistic insights into product template domain function in nonreducing polyketide synthases
Authors: Barajas Jesus F. , Shakya Gaurav , Moreno Gabriel , Rivera Heriberto , Jackson David R. , Topper Caitlyn L. , Vagstad Anna L. , La Clair James J. , Townsend Craig A. , Burkart Michael D. , Tsai Shiou-Chuan 
Published: May 2017

Significance
Product template (PT) domains from fungal nonreducing polyketide synthases (NR-PKSs) are responsible for controlling the aldol cyclizations of poly-β-ketone intermediates during polyketide biosynthesis. Our ability to understand the high regioselective control that PT exerts is hindered by the inaccessibility of unstable poly-β-ketones for in vitro studies. We describe here the crystallographic application of “atom replacement” mimetics in which isoxazole rings linked by thioethers mimic the alternating sites of carbonyls in the poly-β-ketone intermediates. The probe contains a heptaketide mimetic tethered to a modified 4′-phosphopantetheine, which provides important empirical evidence for the PT-catalyzed cyclization mechanism. These findings afford a view of a polyketide “atom-replaced” mimetic in a NR-PKS active site that could prove general for other PKS domains.
Biological origins of color categorization
Authors: Skelton Alice E. , Catchpole Gemma , Abbott Joshua T. , Bosten Jenny M. , Franklin Anna 
Published: May 2017

SignificanceHumans parse the continuum of color into discrete categories (e.g., “red” and “blue”), and the origin of these categories has been debated for many decades. Here, we provide evidence that infants have color categories for red, yellow, green, blue, and purple. We show that infants’ categorical distinctions align strikingly with those that are commonly made in the world’s different color lexicons. We also find that infants’ categorical distinctions relate to the activities of the two neural subsystems responsible for the early stages of color representation. These findings suggest that color categorization is partly organized and constrained by the biological mechanisms of color vision and not arbitrarily constructed by language.
Metaplasticity mechanisms restore plasticity and associativity in an animal model of Alzheimer’s disease
Authors: Li Qin , Navakkode Sheeja , Rothkegel Martin , Soong Tuck Wah , Sajikumar Sreedharan , Korte Martin 
Published: May 2017

Significance
Under physiological conditions, metaplasticity is ideally suited to prepare neuronal networks for encoding specific information, thereby ensuring subsequent learning and long-lasting memory storage. Our memory capacity lies at the heart of all cognitive function, and the correct scaling of synaptic plasticity is vital for normal brain function. Here we present data from amyloid precursor protein (APP)/presenilin-1 (PS1) mice, a mouse model of Alzheimer’s disease, indicating that the failure of neurons to scale the predisposition to undergo plasticity after earlier events (i.e., metaplasticity) might be a determinant for disease onset and progression. Our findings indicate that the induction of metaplasticity by ryanodine receptor activation contributes to the reestablishment of plasticity and associativity in hippocampal neurons of APP/PS1 mice and might be a potential therapeutic target.
Preferences for group dominance track and mediate the effects of macro-level social inequality and violence across societies
Authors: Kunst Jonas R. , Fischer Ronald , Sidanius Jim , Thomsen Lotte 
Published: May 2017

SignificanceIndividuals differ in the degree to which they endorse group-based hierarchies in which some social groups dominate others. Much research demonstrates that among individuals this preference robustly predicts ideologies and behaviors enhancing and sustaining social hierarchies (e.g., racism, sexism, and prejudice). Combining aggregate archival data from 27 countries (n= 41,824) and multilevel data from 30 US states (n= 4,613) with macro-level indicators, we demonstrate that the degree of structural inequality, social instability, and violence in different countries and US states is reflected in their populations’ minds in the form of support of group-based hegemony. This support, in turn, increases individual endorsement of ideologies and behaviors that ultimately sustain group-based inequality, such as the ethnic persecution of immigrants.
Body sway reflects leadership in joint music performance
Authors: Chang Andrew , Livingstone Steven R. , Bosnyak Dan J. , Trainor Laurel J. 
Published: May 2017

Significance
People perform tasks in coordination with others in daily life, but the mechanisms are not well understood. Using Granger causality models to examine string quartet dynamics, we demonstrated that musicians assigned as leaders affect other performers more than musicians assigned as followers. These effects were present during performance, when musicians could only hear each other, but were magnified when they could also see each other, indicating that both auditory and visual cues affect nonverbal social interactions. Furthermore, the overall degree of coupling between musicians was positively correlated with ratings of performance success. Thus, we have developed a method for measuring nonverbal interaction in complex situations and have shown that interaction dynamics are affected by social relations and perceptual cues.
Structural basis for cancer immunotherapy by the first-in-class checkpoint inhibitor ipilimumab
Authors: Ramagopal Udupi A. , Liu Weifeng , Garrett-Thomson Sarah C. , Bonanno Jeffrey B. , Yan Qingrong , Srinivasan Mohan , Wong Susan C. , Bell Alasdair , Mankikar Shilpa , Rangan Vangipuram S. , Deshpande Shrikant , Korman Alan J. , Almo Steven C. 
Published: May 2017

Significance
Biologics represent a major class of therapeutics for the treatment of malignancies, autoimmune diseases, and infectious diseases. Ipilimumab is the first-in-class immunotherapeutic for blockade of CTLA-4 and significantly benefits overall survival of patients with metastatic melanoma. The X-ray crystal structure of the ipilimumab:CTLA-4 complex defines the atomic interactions responsible for affinity and selectivity and demonstrates that the therapeutic action of ipilimumab is due to direct steric competition with the B7 ligands for binding to CTLA-4.
Coronavirus nonstructural protein 15 mediates evasion of dsRNA sensors and limits apoptosis in macrophages
Authors: Deng Xufang , Hackbart Matthew , Mettelman Robert C. , O’Brien Amornrat , Mielech Anna M. , Yi Guanghui , Kao C. Cheng , Baker Susan C. 
Published: May 2017

Significance
Macrophages are immune cells equipped with multiple double-stranded RNA (dsRNA) sensors designed to detect viral infection and amplify innate antiviral immunity. However, many coronaviruses can infect and propagate in macrophages without activating dsRNA sensors. Here we present a function of murine coronavirus nonstructural protein 15 in preventing detection of viral dsRNA by host sensors. We show that coronaviruses expressing a mutant form of nonstructural protein 15 allow for activation of dsRNA sensors, resulting in an early induction of interferon, rapid apoptosis of macrophages, and a protective immune response in mice. Identifying the strategies used by viruses to evade detection provides us with new approaches for generating vaccines that elicit robust innate immune responses and protective immunity.
Dynamic remodeling of the dynamin helix during membrane constriction
Authors: Colom Adai , Redondo-Morata Lorena , Chiaruttini Nicolas , Roux Aurélien , Scheuring Simon 
Published: May 2017

Significance
The GTPase dynamin catalyzes membrane fission and is essential in endocytosis and other events such as organelle division. Dynamin is a unique molecular motor with torsional and contractile abilities. Because these abilities involve a conformational change at the whole-polymer level, standard structural biology tools have not been able to fully unravel the mechanism by which it constricts and twists. Here we used high-speed atomic force microscopy to image the constriction and fission of dynamin-coated tubules with subnanometer and subsecond resolution. Our results provide important findings to establish the contribution of the various constriction mechanisms.
Adaptation of cone pigments found in green rods for scotopic vision through a single amino acid mutation
Authors: Kojima Keiichi , Matsutani Yuki , Yamashita Takahiro , Yanagawa Masataka , Imamoto Yasushi , Yamano Yumiko , Wada Akimori , Hisatomi Osamu , Nishikawa Kanto , Sakurai Keisuke , Shichida Yoshinori 
Published: May 2017

Significance
Anurans are unique in possessing two types of rod photoreceptor cells, red and green rods. Red rods express rhodopsin, whereas green rods express blue-sensitive cone visual pigment. Rhodopsin exhibits a low rate of thermal isomerization of the retinal chromophore, which enables rods to detect photons with extremely high signal-to-noise for scotopic vision. Here, we show that anuran blue-sensitive cone pigments acquired a rhodopsin-like property through a single amino acid mutation at position 47 in the evolutionary process from other cone pigments. Thus, anurans have special blue-sensitive cone pigments for the contribution of green rods to the low threshold of light detection, which could form the molecular basis in tandem with red rods containing rhodopsin in scotopic color vision.
Erythritol is a pentose-phosphate pathway metabolite and associated with adiposity gain in young adults
Authors: Hootman Katie C. , Trezzi Jean-Pierre , Kraemer Lisa , Burwell Lindsay S. , Dong Xiangyi , Guertin Kristin A. , Jaeger Christian , Stover Patrick J. , Hiller Karsten , Cassano Patricia A. 
Published: May 2017

SignificanceThe prevention of weight gain in adulthood is a public health challenge, particularly given the difficulty of losing weight. Data on freshmen were collected at the beginning and end of the academic year, and baseline blood samples were studied to find markers of incident weight gain. A metabolite, erythritol, was elevated at the beginning of the year in freshmen who went on to gain weight, fat, and abdominal fat compared with freshmen with stable weight. Erythritol is a sugar substitute low-calorie sweetener, and prior studies claimed no endogenous synthesis. We report a previously unrecognized metabolism of glucose to erythritol, and given the association between erythritol and weight gain, research is needed to understand whether and how this pathway contributes to weight gain risk.
Selective targeting of point-mutated KRAS through artificial microRNAs
Authors: Acunzo Mario , Romano Giulia , Nigita Giovanni , Veneziano Dario , Fattore Luigi , Laganà Alessandro , Zanesi Nicola , Fadda Paolo , Fassan Matteo , Rizzotto Lara , Kladney Raleigh , Coppola Vincenzo , Croce Carlo M. 
Published: May 2017

Significance
Recently, small interfering RNAs have been used to specifically target point-mutated KRAS, yet without sufficiently discriminating its wild-type counterpart. Here, we describe an innovative approach based on the development of artificial microRNAs able to efficiently target mutated KRAS, leaving their normal counterpart unaffected and preventing major side effects.
Heritability analysis with repeat measurements and its application to resting-state functional connectivity
Authors: Ge Tian , Holmes Avram J. , Buckner Randy L. , Smoller Jordan W. , Sabuncu Mert R. 
Published: May 2017

Significance
Heritability is a fundamental metric in population genetics. Existing heritability models lump together stable effects (e.g., due to the subject’s unique environment) and transient effects, such as measurement error. This can result in misleading assessments when comparing the heritability of traits that exhibit different levels of reliability. This paper presents a heritability estimation strategy that can account for transient intrasubject variation using repeat measurements. Using the proposed method, we show that the stable components of functional connectivity within and across well-established large-scale brain networks can be considerably heritable. With the explosive expansion of genomics, health informatics, and digital phenotyping technologies, the proposed model will be significant in dissecting the genetic basis of a wide range of informative but noisy phenotypes.
Common general anesthetic propofol impairs kinesin processivity
Authors: Bensel Brandon M. , Guzik-Lendrum Stephanie , Masucci Erin M. , Woll Kellie A. , Eckenhoff Roderic G. , Gilbert Susan P. 
Published: May 2017

Significance
Kinesins are major transporters of cargos toward the cell periphery. They are highly expressed in the CNS, and their dysfunction leads to a wide range of human pathologies, including neurodevelopmental and neurodegenerative diseases, ciliopathies, epilepsy, and birth defects. We have discovered that the widely used general anesthetic propofol shortens the distance that kinesins travel, but their velocity remains unchanged. These results suggest that propofol is not binding at the ATP site or allosteric sites that affect ATP turnover, leading to the conclusion that the allosteric sites form on microtubule association. We postulate that general anesthetics bind specifically to transport kinesins and/or the kinesin–β-tubulin interface, and diminish their ability to transport critical cargos, thereby contributing to the pleiotropic state of anesthesia.
Modeling the response of a tumor-suppressive network to mitogenic and oncogenic signals
Authors: Tian Xinyu , Huang Bo , Zhang Xiao-Peng , Lu Mingyang , Liu Feng , Onuchic José N. , Wang Wei 
Published: May 2017

Significance
Mammalian cells have evolved to develop multiple mechanisms for tumor suppression. It remains challenging to dissect the dynamic mechanism by which signaling proteins are engaged in inhibiting aberrant cell proliferation. Here, we propose a comprehensive network model composed of three signaling pathways and show how this network responds to mitogenic and oncogenic signals. This modeling approach elucidates how a precise temporal control of signaling pathways modulates the cellular response. We reveal the underlying principle for cell-fate decision and identify the roles of the different network components in tumor inhibition. This study sheds light on how the tumor-suppressive function can be modulated by the dynamics of the signaling proteins.