bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneous formation of nanoparticles on electrospun nanofibres
Authors: Radacsi Norbert , Campos Fernando Diaz , Chisholm Calum R. I. , Giapis Konstantinos P. 
Published: November 2018

AbstractWe report the spontaneous formation of nanoparticles on smooth nanofibres in a single-step electrospinning process, as an inexpensive and scalable method for producing high-surface-area composites. Layers of nanofibres, containing the proton conducting electrolyte, caesium dihydrogen phosphate, are deposited uniformly over large area substrates from clear solutions of the electrolyte mixed with polymers. Under certain conditions, the normally smooth nanofibres develop caesium dihydrogen phosphate nanoparticles in large numbers on their external surface. The nanoparticles appear to originate from the electrolyte within the fibres, which is transported to the outer surface after the fibres are deposited, as evidenced by cross-sectional imaging of the electrospun fibres. The presence of nanoparticles on the fibre surface yields composites with increased surface area of exposed electrolyte, which ultimately enhances electrocatalytic performance. Indeed, solid acid fuel cells fabricated with electrodes from processed nanofibre-nanoparticle composites, produced higher cell voltage as compared to fuel cells fabricated with state-of-the-art electrodes.
Design and 22-step synthesis of highly potent D-ring modified and linker-equipped analogs of spongistatin 1
Authors: Suen Linda M. , Tekle-Smith Makeda A. , Williamson Kevin S. , Infantine Joshua R. , Reznik Samuel K. , Tanis Paul S. , Casselman Tyler D. , Sackett Dan L. , Leighton James L. 
Published: November 2018

AbstractSpongistatin 1 is among the most potent anti-proliferative agents ever discovered rendering it an attractive candidate for development as a payload for antibody–drug conjugates and other targeted delivery approaches. Unfortunately, it is unavailable from natural sources and its size and complex stereostructure render chemical synthesis highly time- and resource-intensive. As a result, the design and synthesis of more acid-stable and linker functional group-equipped analogs that retain the low picomolar potency of the parent natural product requires more efficient and step-economical synthetic access. Using uniquely enabling direct complex fragment coupling crotyl- and alkallylsilylation reactions, we report a 22-step synthesis of a rationally designed D-ring modified analog of spongistatin 1 that is characterized by GI50 values in the low picomolar range, and a proof-of-concept result that the C(15) acetate may be replaced with linker functional group-bearing esters with only minimal reductions in potency.
Thermochronological insights into reactivation of a continental shear zone in response to Equatorial Atlantic rifting (northern Ghana)
Authors: Fernie Nicholas , Glorie Stijn , Jessell Mark W. , Collins Alan S. 
Published: November 2018

AbstractWest Africa was subjected to deformation and exhumation in response to Gondwana break-up. The timing and extent of these events are recorded in the thermal history of the margin. This study reports new apatite fission track (AFT) data from Palaeoproterozoic basement along the primary NE-SW structural trend of the Bole-Nangodi shear zone in northwestern Ghana. The results display bimodality in AFT age (populations of ~210-180 Ma and ~115-105 Ma) and length distributions (populations of 12.2 ± 1.6 and 13.1 ± 1.4 µm), supported by differences in apatite chemistry (U concentrations). The bimodal AFT results and associated QTQt thermal history models provide evidence for multiple cooling phases. Late Triassic – Early Jurassic cooling is interpreted to be related with thermal relaxation after the emplacement of the Central Atlantic Magmatic Province (CAMP). Early to middle Cretaceous cooling is thought to be associated with exhumation during the Cretaceous onset of rifting between West Africa and Brazil. Late Cretaceous – Cenozoic cooling can be related with exhumation of the Ivory Coast – Ghana margin and NNW-SSE shortening through western Africa. Furthermore, our data record differential exhumation of the crust with respect to the Bole-Nangodi shear zone, preserving older (CAMP) cooling ages to the south and younger (rifting) cooling ages to the north of the shear zone, respectively. This suggests that the Palaeoproterozoic BN shear zone was reactivated during the Cretaceous as a result of deformation in the Equatorial Atlantic region of Africa.
Amyloid precursor protein-fragments-containing inclusions in cardiomyocytes with basophilic degeneration and its association with cerebral amyloid angiopathy and myocardial fibrosis
Authors: Krämer Lara Maria , Brettschneider Johannes , Lennerz Jochen K. , Walcher Daniel , Fang Lubin , Rosenbohm Angela , Balakrishnan Karthikeyan , Benckendorff Julian , Möller Peter , Just Steffen , Willem Michael , Ludolph Albert C. , Thal Dietmar Rudolf 
Published: November 2018

AbstractCardiomyopathies with intracellular inclusions are a distinct subset of cardiomyopathies whereas basophilic degeneration (BD) of the heart describes inclusions in cardiomyocytes of the aging heart, which have not yet been related to a specific disease condition or to a distinct type of protein inclusion. To address the question whether BD represents a specific pathological feature and whether it is linked to a distinct disease condition we studied 62 autopsy cases. BD inclusions exhibited an immunohistochemical staining pattern related to glycosylated, δ- or η-secretase-derived N-terminal cleavage products of the amyloid precursor protein (sAPPδ/η) or shorter fragments of sAPPη. BD aggregates were found in the myocardium of both ventricles and atria with highest amounts in the atria and lowest in the interventricular septum. The frequency of BD-lesions correlated with age, degree of myocardial fibrosis in individuals with arterial hypertension, and the severity of cerebral amyloid angiopathy (CAA). The intracytoplasmic deposition of N-terminal sAPPδ/η fragments in BD indicates a specific inclusion body pathology related to APP metabolism. The correlation with the severity of CAA, which is related to the APP-derived amyloid β-protein, supports this point of view and suggests a possible link between myocardial and cerebrovascular APP-related lesions.
Functional analysis of potential cleavage sites in the MERS-coronavirus spike protein
Authors: Kleine-Weber Hannah , Elzayat Mahmoud Tarek , Hoffmann Markus , Pöhlmann Stefan 
Published: November 2018

AbstractThe Middle East respiratory syndrome-related coronavirus (MERS-CoV) can cause severe disease and has pandemic potential. Therefore, development of antiviral strategies is an important task. The activation of the viral spike protein (S) by host cell proteases is essential for viral infectivity and the responsible enzymes are potential therapeutic targets. The cellular proteases furin, cathepsin L and TMPRSS2 can activate MERS-S and may cleave the S protein at two distinct sites, termed S1/S2 and S2′. Moreover, a potential cathepsin L cleavage site in MERS-S has been reported. However, the relative importance of these sites for MERS-S activation is incompletely understood. Here, we used mutagenic analysis and MERS-S-bearing vectors to study the contribution of specific cleavage sites to S protein-driven entry. We found that an intact S1/S2 site was only required for efficient entry into cells expressing endogenous TMPRSS2. In keeping with a previous study, pre-cleavage at the S1/S2 motif (RSVR) was important although not essential for subsequent MERS-S activation by TMPRSS2, and indirect evidence was obtained that this motif is processed by a protease depending on an intact RXXR motif, most likely furin. In contrast, the S2′ site (RSAR) was required for robust viral entry into all cell lines tested and the integrity of one of the two arginines was sufficient for efficient entry. These findings suggest that cleavage at S2′ is carried out by proteases recognizing a single arginine, most likely TMPRSS2 and cathepsin L. Finally, mutation of the proposed cathepsin L site did not impact viral entry and double mutation of S1/S2 and S2′ site was compatible with cathepsin L- but not TMPRSS2-dependent host cell entry, indicating that cathepsin L can process the S protein at auxiliary sites. Collectively, our results indicate a rigid sequence requirement for S protein activation by TMPRSS2 but not cathepsin L.
Structure analysis and antiviral activity of CW-33 analogues against Japanese encephalitis virus
Authors: Lien Jin-Cherng , Wang Ching-Ying , Lai Hsueh–Chou , Lu Chien-Yi , Lin Yu-Fong , Gao Ging-Yan , Chen Kuan-Chung , Huang An-Cheng , Huang Su-Hua , Lin Cheng-Wen 
Published: November 2018

AbstractJapanese encephalitis virus (JEV) is a member of neurotropic flaviviruses transmitted by mosquito bites, causing severe central nervous system disorders. Current JEV genotype III vaccines have a low protection against genotype I isolates in the risk zone. The lead compound CW-33, ethyl 2-(3′,5′-dimethylanilino)-4-oxo-4,5-dihydrofuran-3-carboxylate, demonstrates the antiviral activity against JEV with an IC50 values of 38.5 μM for virus yield reduction (Int J Mol Sci 2016,17: E1386). This study synthesized fourteen CW-33 analogues containing a fluoro atom or one methoxy group at the C-2, C-3, or C-4 of anilino ring, and then evaluated for their antiviral activity and mechanism. Among 6 amalogues, CW-33A (ethyl 2-(2-fluoroanilino)-4-oxo- 4,5-dihydrofuran-3-carboxylate), and CW-33D (ethyl 2-(3-methoxyanilino)-4-oxo- 4,5-dihydrofuran-3-carboxylate exhibited antiviral potentials in viral cytopathic effect (CPE) inhibition. CW-33A significantly suppressed the viral protein expression, genome synthesis and intracellular JEV particle production, showing a higher inhibitory effect on JEV yield than CW-33 and CW-33D. The study demonstrated that a mono-fluoro substitution on at the C-2 anilino ring of CW-33 improved the antiviral activity JEV, revealing the structure-activity relationship for developing novel agents against JEV infection.
The two phases of the Cambrian Explosion
Authors: Zhuravlev Andrey Yu. , Wood Rachel A. 
Published: November 2018

AbstractThe dynamics of how metazoan phyla appeared and evolved – known as the Cambrian Explosion – remains elusive. We present a quantitative analysis of the temporal distribution (based on occurrence data of fossil species sampled in each time interval) of lophotrochozoan skeletal species (n = 430) from the terminal Ediacaran to Cambrian Stage 5 (~545 – ~505 Million years ago (Ma)) of the Siberian Platform, Russia. We use morphological traits to distinguish between stem and crown groups. Possible skeletal stem group lophophorates, brachiopods, and molluscs (n = 354) appear in the terminal Ediacaran (~542 Ma) and diversify during the early Cambrian Terreneuvian and again in Stage 2, but were devastated during the early Cambrian Stage 4 Sinsk extinction event (~513 Ma) never to recover previous diversity. Inferred crown group brachiopod and mollusc species (n = 76) do not appear until the Fortunian, ~537 Ma, radiate in the early Cambrian Stage 3 (~522 Ma), and with minimal loss of diversity at the Sinsk Event, continued to diversify into the Ordovician. The Sinsk Event also removed other probable stem groups, such as archaeocyath sponges. Notably, this diversification starts before, and extends across the Ediacaran/Cambrian boundary and the Basal Cambrian Carbon Isotope Excursion (BACE) interval (~541 to ~540 Ma), ascribed to a possible global perturbation of the carbon cycle. We therefore propose two phases of the Cambrian Explosion separated by the Sinsk extinction event, the first dominated by stem groups of phyla from the late Ediacaran, ~542 Ma, to early Cambrian stage 4, ~513 Ma, and the second marked by radiating bilaterian crown group species of phyla from ~513 Ma and extending to the Ordovician Radiation.
Changes in canine serum N-glycosylation as a result of infection with the heartworm parasite Dirofilaria immitis
Authors: Behrens Anna-Janina , Duke Rebecca M. , Petralia Laudine M. C. , Lehoux Sylvain , Carlow Clotilde K. S. , Taron Christopher H. , Foster Jeremy M. 
Published: November 2018

AbstractFilariases are diseases caused by infection with filarial nematodes and transmitted by insect vectors. The filarial roundwormDirofilaria immitiscauses heartworm disease in dogs and other carnivores.D. immitisis closely related toOnchocerca volvulus,Wuchereria bancroftiandBrugia malayi, which cause onchocerciasis (river blindness) and lymphatic filariasis (elephantiasis) in humans and are neglected tropical diseases. Serum N-glycosylation is very sensitive to both pathological infections and changes in mammalian biology due to normal aging or lifestyle choices. Here, we report significant changes in the serum N-glycosylation profiles of dogs infected withD. immitis. Our data derive from analysis of serum from dogs with established patent infections and from a longitudinal infection study. Overall, galactosylation and core fucosylation increase, while sialylation decreases in infected dog sera. We also identify individual glycan structures that change significantly in their relative abundance during infection. Notably, the abundance of the most dominant N-glycan in canine serum (biantennary, disialylated A2G2S2) decreases by over 10 percentage points during the first 6 months of infection in each dog analyzed. This is the first longitudinal study linking changes in mammalian serum N-glycome to progression of a parasitic infection.
Geographical and temporal distribution of the residual clusters of human leptospirosis in China, 2005–2016
Authors: Dhewantara Pandji Wibawa , Mamun Abdullah Al , Zhang Wen-Yi , Yin Wen-Wu , Ding Fan , Guo Danhuai , Hu Wenbiao , Magalhães Ricardo J. Soares 
Published: November 2018

AbstractHuman leptospirosis outbreaks still persistently occur in part of China, indicating that leptospirosis remains an important zoonotic disease in the country. Spatiotemporal pattern of the high-risk leptospirosis cluster and the key characteristics of high-risk areas for leptospirosis across the country are still poorly understood. Using spatial analytical approaches, we analyzed 8,158 human leptospirosis cases notified during 2005–2016 across China to explore the geographical distribution of leptospirosis hotspots and to characterize demographical, ecological and socioeconomic conditions of high-risk counties for leptospirosis in China. During the period studied, leptospirosis incidence was geographically clustered with the highest rate observed in the south of the Province of Yunnan. The degree of spatial clustering decreased over time suggesting changes in local risk factors. However, we detected residual high-risk counties for leptospirosis including counties in the southwest, central, and southeast China. High-risk counties differed from low-risk counties in terms of its demographical, ecological and socioeconomic characteristics. In high-risk clusters, leptospirosis was predominantly observed on younger population, more males and farmers. Additionally, high-risk counties are characterized by larger rural and less developed areas, had less livestock density and crops production, and located at higher elevation with higher level of precipitation compare to low-risk counties. In conclusion, leptospirosis distribution in China appears to be highly clustered to a discrete number of counties highlighting opportunities for elimination; hence, public health interventions should be effectively targeted to high-risk counties identified in this study.
ROCK2, but not ROCK1 interacts with phosphorylated STAT3 and co-occupies TH17/TFH gene promoters in TH17-activated human T cells
Authors: Chen Wei , Nyuydzefe Melanie S. , Weiss Jonathan M. , Zhang Jingya , Waksal Samuel D. , Zanin-Zhorov Alexandra 
Published: November 2018

AbstractRho-associated coiled-coil kinase (ROCK)2 targeting down-regulates autoimmune responses in animal models and patients, however the underlying molecular mechanism is still an enigma. We report that ROCK2 binds phosphorylated-STAT3 and its kinase activity controls the formation of ROCK2/STAT3/JAK2 complex and optimal STAT3 phosphorylation in human CD4+ T cells during T helper 17 (TH17)-skewing. Moreover, chromatin-immunoprecipitation sequencing (ChIP-seq) analysis revealed that, genome-wide, about 70% of ROCK2 and STAT3 peaks overlapped and co-localized to several key genes controlling TH17 and T follicular helper (TFH) cell functions. Specifically, the co-occupancy of ROCK2 and STAT3 on the Irf4 and Bcl6 genes was validated by ChIP-qPCR analysis. Furthermore, the binding of ROCK2 to both the Irf4 and Bcl6 promoters was attenuated by STAT3 silencing as well as by selective ROCK2 inhibitor. Thus, the present study demonstrated previously unidentified evidence that ROCK2-mediated signaling in the cytosol provides a positive feed-forward signal for nuclear ROCK2 to be recruited to the chromatin by STAT3 and potentially regulates TH17/TFH gene transcription.
Ten-year experience of tricuspid valve replacement with the St. Jude medical valve
Authors: Zhu Xiliang , Luo Yi , Zhang Eryong , An Qi , Xiao Xijun , Dong Li , Guo Yingqiang , Dian Ke , Wu Zhong 
Published: November 2018

AbstractBioprosthetic valves for tricuspid valve replacement (TVR) have become increasingly popular in recent years, but mechanical valves remain valuable, particularly for the patients who want to avoid reoperation for bioprostheses malfunction. The aim of this study was to review our 10-year experience in adult patients who underwent TVR with the St. Jude Medical (SJM) valve. From 2005 to 2015, 265 TVRs with SJM valves were performed at our institution. The mean age at operation was 44.1 ± 9.7 years, and 207 cases (78.1%) were female. The mean follow-up was 4.9 ± 2.7 years. Preoperative atrial fibrillation was present in 199 cases (75.1%) and ascites in 26 (9.8%). Of all cases, 88.7% were characterized as New York Heart Association class III or IV. The hospital mortality was 6.4%. There were 9 deaths (3.8%) during late follow-up. The overall survival rates were 89.2% ± 2.2% at 5 years and 86.6% ± 2.9% at 10 years. The linearized rates of valve thrombosis and bleeding events were 0.8%/patient-year and 1.5%/patient-year, respectively. Three cases (1.3%) were reoperated due to prosthetic valve thrombosis. There was no reoperation for sperivalvular leakage and structural failure. The freedom from reoperation was 98.6% ± 0.8% at 5 years and 98.6% ± 0.8% at 10 years. The SJM valve in the tricuspid position is a reliable mechanical prosthesis with a low rate of valve thrombosis and reoperation. It is a reasonable choice for the patients who require mechanical valve replacement in the tricuspid position.
Breakdown of diffusivity–entropy scaling in colloidal glass-forming liquids
Authors: Li Bo , Xiao Xiuming , Lou Kai , Wang Shuxia , Wen Weijia , Wang Ziren 
Published: November 2018

AbstractGlass is a liquid that has lost its ability to flow. Why this particular substance undergoes such a dramatic kinetic slowdown yet remains barely distinguishable in structure from its fluid state upon cooling constitutes the central question of glass transition physics. Here, we investigate the pathway of kinetic slowdown in glass-forming liquids that consist of monolayers of ellipsoidal or binary spherical colloids. In contrast to rotational motion, the dynamics of the translational motion begin to violently slow down at considerably low area fractions (ϕT). At ϕT, anomalous translation–rotation coupling is enhanced and the topography of the free energy landscape become rugged. Based on the positive correlation between ϕT and fragility, the measurement of ϕT offers a novel method for predicting glassy dynamics, circumventing the prohibitive increase in equilibrium times required in high-density regions. Our results highlight the role that thermodynamical entropy plays in glass transitions.
Kommunikation ist das, was ankommt
Authors: Schäfer P. Klaus 
Published: November 2018

ZusammenfassungMedizinisches und pflegerisches Fachpersonal auf Intensivstationen übernimmt eine
wichtige Rolle in der Kommunikation mit den Angehörigen der meist
schwerstkranken Patienten. Das gilt vor allem dann, wenn über Koma, Tod oder
Hirntod gesprochen wird. Unser Autor schildert die gängigsten Missverständnisse
und wie man korrekt formuliert.
BRAF V600E and Retinoic Acid in Radioiodine-Refractory Papillary Thyroid Cancer
Authors: Groener Jan , Gelen Debora , Mogler Carolin , Herpel Esther , Toth Csaba , Kender Zoltan , Peichl Marco , Haufe Sabine , Haberkorn Uwe , Sulaj Alba , Zemva Johanna , Kopf Stefan , Nawroth Peter , Brune Maik , Rudofsky Gottfried 
Published: November 2018

AbstractRadioiodine refractoriness in differentiated thyroid cancer remains an unsolved therapeutic problem. Response to retinoids might depend on specific genetic markers. In this retrospective analysis, associations between BRAF V600E and clinical outcomes after redifferentiation with retinoic acid (RA) and radioiodine therapy (RIT) were investigated. Thirteen patients with radioiodine-refractory (RAI-R) papillary thyroid cancer (PTC) were treated with 13-cis-RA followed by iodine-131 treatment at the Department of Endocrinology, Heidelberg University Hospital, Heidelberg, Germany. DNA sequencing was performed in formalin-fixed paraffin-embedded tissue. Clinical outcome parameters were tumor size, thyroglobulin, and radioiodine uptake in correlation to mutational status. Differences of each parameter were compared before and after RA/RIT. Initial response showed no difference in patients with BRAF V600E compared to patients with wild type. However, after a median follow-up of 2 and a half years, 2 out of 3 patients with BRAF V600E showed response compared to 5 out of 9 with wild type under consideration of all 3 parameters. In this small cohort, more RAI-R PTC patients with BRAF V600E receiving redifferentiation therapy showed response. Verification in a larger study population analyzing mutational status in patients with RAI-R PTC might be helpful to identify patients where redifferentiation therapy might lead to an improved outcome.
Direct Trifluoromethylthiolation Reactions Involving Radical Processes
Authors: Dagousset Guillaume , Barthelemy Anne-Laure , Magnier Emmanuel 
Published: November 2018

An overview of the most significant radical-based synthetic methods currently available for the preparation of trifluoromethylthiolated compounds is presented.1	Introduction2	Early Work: Photochemical Reactions Under UV Irradiation2.1	Reactions Involving CF3SH2.2	Reactions Involving CF3SCl2.3	Reactions Involving CF3SSCF3
3	Reactions Involving a Nucleophilic SCF3 Reagent3.1	Reactions with CuSCF3
3.2	Reactions with AgSCF3
4	Reactions Involving an Electrophilic SCF3 Reagent4.1	Reactions Involving the Formation of an R• Radical4.2	Reactions involving the formation of •SCF3 Radical5	Conclusion