bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Plasmodium PI(4)K inhibitor KDU691 selectively inhibits dihydroartemisinin-pretreated Plasmodium falciparum ring-stage parasites
Authors: Dembele L. , Ang X. , Chavchich M. , Bonamy G. M. C. , Selva J. J. , Lim M. Yi-Xiu , Bodenreider C. , Yeung B. K. S. , Nosten F. , Russell B. M. , Edstein M. D. , Straimer J. , Fidock D. A. , Diagana T. T. , Bifani P. 
Published: May 2017

AbstractMalaria control and elimination are threatened by the emergence and spread of resistance to artemisinin-based combination therapies (ACTs). Experimental evidence suggests that when an artemisinin (ART)-sensitive (K13 wild-type) Plasmodium falciparum strain is exposed to ART derivatives such as dihydroartemisinin (DHA), a small population of the early ring-stage parasites can survive drug treatment by entering cell cycle arrest or dormancy. After drug removal, these parasites can resume growth. Dormancy has been hypothesized to be an adaptive physiological mechanism that has been linked to recrudescence of parasites after monotherapy with ART and, possibly contributes to ART resistance. Here, we evaluate the in vitro drug sensitivity profile of normally-developing P. falciparum ring stages and DHA-pretreated dormant rings (DP-rings) using a panel of antimalarial drugs, including the Plasmodium phosphatidylinositol-4-OH kinase (PI4K)-specific inhibitor KDU691. We report that while KDU691 shows no activity against rings, it is highly inhibitory against DP-rings; a drug effect opposite to that of ART. Moreover, we provide evidence that KDU691 also kills DP-rings of P. falciparum ART-resistant strains expressing mutant K13.
Analytical consideration of liquid droplet impingement on solid surfaces
Authors: Yonemoto Yukihiro , Kunugi Tomoaki 
Published: May 2017

AbstractIn industrial applications involving spray-cooling, combustion, and so on, prediction of the maximum spreading diameter of a droplet impinging on a solid surface permits a quantitative estimation of heat removal and energy consumption. However, although there are many experimental studies regarding droplet impingement behaviour, theoretical models have an applicability limit for predicting the maximum spreading diameter. In the present study, we have developed an analytical model for droplet impingement based on energy conservation that considers adhesion energy in both horizontal and vertical directions at the contact line. The theory is validated by our experiment and existing experimental data possessing a wide range of Weber numbers. We demonstrate that our model can predict βm (i.e., the maximum spreading diameter normalised in terms of initial droplet diameter) for various Newtonian liquids ranging from micro- to millimetre-sized droplets on different solid surfaces and can determine the transition between capillary and viscous regimes. Furthermore, theoretical relations for scaling laws observed by many researchers are derived.
A novel gravity-driven nanofibrous membrane for point-of-use water disinfection: polydopamine-induced in situ silver incorporation
Authors: Wang Jianqiang , Wu Yichao , Yang Zhe , Guo Hao , Cao Bin , Tang Chuyang Y. 
Published: May 2017

AbstractWe report a facile method for preparing silver-loaded membranes for point-of-use disinfection and disaster relief applications. A bio-inspired material, polydopamine, was coated onto a highly porous nanofibrous polyacrylonitrile substrate. We then take advantage of the redox properties of polydopamine to form silver nanoparticles in situ. These nanoparticles were uniformly distributed on the surface of nanofibers with no apparent agglomeration at a silver loading up to 4.36 wt.% (cPAN-Ag1.5). The silver-incorporated membrane cPAN-Ag1.5 achieved a high pure water flux of 130 Lm−2 h−1 at 10-cm water head, demonstrating the feasibility of energy-efficient gravity-driven filtration and eliminating the need for electrical power. The strong anti-bacterial activity and high physical rejection of the membrane led to an excellent disinfection power, with no viable bacterial cells detected in its permeate water. The membrane exhibited >7 log reduction for E. coli and >6 log reduction for B. subtilis. The strategy reported here provides an efficient and green route to synthesize point-of-use membranes. Combining their excellent permeability and disinfection effectiveness, these membranes offer an ideal solution to water supply in disaster-affected areas.
Nano-assembly of amyloid β peptide: role of the hairpin fold
Authors: Maity Sibaprasad , Hashemi Mohtadin , Lyubchenko Yuri L. 
Published: May 2017

AbstractStructural investigations have revealed that β hairpin structures are common features in amyloid fibrils, suggesting that these motifs play an important role in amyloid assembly. To test this hypothesis, we characterized the effect of the hairpin fold on the aggregation process using a model β hairpin structure, consisting of two Aβ(14–23) monomers connected by a turn forming YNGK peptide. AFM studies of the assembled aggregates revealed that the hairpin forms spherical structures whereas linear Aβ(14–23) monomers form fibrils. Additionally, an equimolar mixture of the monomer and the hairpin assembles into non-fibrillar aggregates, demonstrating that the hairpin fold dramatically changes the morphology of assembled amyloid aggregates. To understand the molecular mechanism underlying the role of the hairpin fold on amyloid assembly, we performed single-molecule probing experiments to measure interactions between hairpin and monomer and two hairpin complexes. The studies reveal that the stability of hairpin-monomer complexes is much higher than hairpin-hairpin complexes. Molecular dynamics simulations revealed a novel intercalated complex for the hairpin and monomer and Monte Carlo modeling further demonstrated that such nano-assemblies have elevated stability compared with stability of the dimer formed by Aβ(14–23) hairpin. The role of such folding on the amyloid assembly is also discussed.
Using bicistronic constructs to evaluate the chaperone activities of heat shock proteins in cells
Authors: San Gil Rebecca , Berg Tracey , Ecroyd Heath 
Published: May 2017

AbstractHeat shock proteins (Hsps) are molecular chaperones that prevent the aggregation of client proteins by facilitating their refolding, or trafficking them for degradation. The chaperone activities of Hsps are dependent on dynamic protein-protein interactions, including their oligomerisation into large multi-subunit complexes. Thus, tagging Hsps with fluorescent proteins can interfere with their chaperone activity. To overcome this limitation, we have exploited bicistronic constructs for the concurrent expression of a non-tagged Hsp and fluorescent reporter from a single mRNA in cells. We used the Hsp-encoding bicistronic constructs in a cell-based model of protein aggregation, using a destabilised (mutant) form of firefly luciferase (mFluc) that forms inclusion bodies in cells. Expression of Hsp40, Hsp70, or Hsp40 and Hsp70 in cells expressing mFluc decreased the formation of inclusion bodies by 25–46% compared to controls. Moreover, there was a concentration-dependent decrease in the proportion of cells with inclusions when Hsp70, or Hsp40 and Hsp70 were co-expressed with mFluc in cells. The Hsp-encoding bicistronic constructs enable transfection efficiencies and concentration-dependent effects of Hsp expression to be determined using fluorescence based techniques, without the need to tag the Hsp with a fluorescent protein.
Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice
Authors: Liao Lifan , Zhang Shanxing , Gu Jianhong , Takarada Takeshi , Yoneda Yukio , Huang Jian , Zhao Lan , Oh Chun-do , Li Jun , Wang Baoli , Wang Meiqing , Chen Di 
Published: May 2017

AbstractRunx2 may play an important role in development of osteoarthritis (OA). However, the specific role of Runx2 in articular chondrocyte function and in OA development in adult mice has not been fully defined. In this study, we performed the destabilization of the medial meniscus (DMM) surgery at 12-week-old mice to induce OA in adult Runx2
Agc1CreER
mice, in which Runx2 was specifically deleted in Aggrecan-expressing chondrocytes by administering tamoxifen at 8-weeks of age. Knee joint samples were collected 8- and 12-weeks post-surgery and analyzed through histology, histomorphometry and micro-computed tomography (μCT). Our results showed that severe OA-like defects were observed after DMM surgery in Cre-negative control mice, including articular cartilage degradation and subchondral sclerosis, while the defects were significantly ameliorated in Runx2
Agc1CreER
KO mice. Immunohistochemical (IHC) results showed significantly reduced expression of MMP13 in Runx2
Agc1CreER
KO mice compared to that in Cre-negative control mice. Results of quantitative reverse-transcription PCR (qRT-PCR) demonstrated that expression of the genes encoding for matrix degradation enzymes was significantly decreased in Runx2
Agc1CreER
KO mice. Thus, our findings suggest that inhibition of Runx2 in chondrocytes could at least partially rescue DMM-induced OA-like defects in adult mice.
The “inherent vice” in the anti-angiogenic theory may cause the highly metastatic cancer to spread more aggressively
Authors: Wang Denian , Tan Chun , Xiao Fei , Zou Lan , Wang Lijun , Wei Yong’gang , Yang Hanshuo , Zhang Wei 
Published: May 2017

AbstractAlthough anti-angiogenic (AA) therapy is widely used in clinical practice, it is often challenged by insufficient efficacy and intrinsic resistance. Some studies have reported that AA therapy can even increase tumor metastasis. However, whether this is due to a specific AA drug causing a specific tumor to metastasize or because the anti-angiogenic theory has some “inherent vice” that may inevitably lead to tumor dissemination remains a mystery. Herein, we designed a model that completely blocks tumor blood supply using a physical barrier to examine tumor behavior in such circumstances. Surprisingly, we found that cutting off the blood supply could neither eliminate the primary tumor cells nor prevent local invasion or formation of distant metastases. By using a mathematical method to simulate tumor behavior, we found that blocking tumor blood supply may lead to an inevitable consequence: the cells that can tolerate blood deficiency are “naturally selected” and survive, whereas a portion of cells are promoted to escape from the “starvation” area by the consistent environmental stress until they are spread throughout the body. This may be an intrinsic disadvantage of the AA strategy, which will inevitably cause the tumor, particularly highly metastatic tumors, to spread more aggressively.
Component analysis of somatosensory evoked potentials for identifying spinal cord injury location
Authors: Wang Yazhou , Li Guangsheng , Luk Keith D. K. , Hu Yong 
Published: May 2017

AbstractThis study aims to determine whether the time-frequency components (TFCs) of somatosensory evoked potentials (SEPs) can be used to identify the specific location of a compressive spinal cord injury using a classification technique. Waveforms of SEPs after compressive injuries at various locations (C4, C5 and C6) in rat spinal cords were decomposed into a series of TFCs using a high-resolution time-frequency analysis method. A classification method based on support vector machine (SVM) was applied to the distributions of these TFCs among different pathological locations. The difference among injury locations manifests itself in different categories of SEP TFCs. High-energy TFCs of normal-state SEPs have significantly higher power and frequency than those of injury-state SEPs. The location of C5 is characterized by a unique distribution pattern of middle-energy TFCs. The difference between C4 and C6 is evidenced by the distribution pattern of low-energy TFCs. The proposed classification method based on SEP TFCs offers a discrimination accuracy of 80.2%. In this study, meaningful information contained in various SEP components was investigated and used to propose a new application of SEPs for identification of the location of pathological changes in the cervical spinal cord.
ANO1 inhibits cardiac fibrosis after myocardial infraction via TGF-β/smad3 pathway
Authors: Gao Yao , Zhang Yan Mei , Qian Li Jun , Chu Ming , Hong Jian , Xu Di 
Published: May 2017

AbstractAs a newly identified factor in calcium-activated chloride channel, ANO1 participates in various physiological processes like proliferation and differentiation, and expresses in human cardiac fibroblasts. In this experiment, we investigated the function of ANO1 in cardiac fibrosis after myocardial infraction (MI) with methods of Western blotting, Quantitative real-time PCR (qRT-PCR), metabolic reduction of 3-(4,5-dimethylthiozol-2-yl)-2, 5-diphenyltetrazo-lium bromide (MTT), immunofluorescence and confocal imaging, and Masson’s trichrome staining. The results showed that the expression of ANO1 significantly increased in neonatal rats’ cardiac fibroblasts after hypoxia and in cardiac tissues after MI. After ANO1 over-expression, cardiac fibrosis was reduced in vitro and in vivo. Moreover, the expression of TGF-β and p-smad3 declined after ANO1over-expression in cardiac fiborblasts. In conclusion, ANO1 inhibits cardiac fibrosis after MI via TGF-β/smad3 pathway in rats.
The PB2 mutation with lysine at 627 enhances the pathogenicity of avian influenza (H7N9) virus which belongs to a non-zoonotic lineage
Authors: Li Weixuan , Lee Horace Hok Yeung , Li Run Feng , Zhu Huachen Maria , Yi Guan , Peiris Joseph Sriyal Malik , Yang Zi Feng , Mok Chris Ka Pun 
Published: May 2017

AbstractA novel avian-origin influenza A (H7N9) virus emerged in China in 2013 and has caused zoonotic disease in over 1123 persons with an overall mortality around 30%. Amino acid changes at the residues 591, 627 and 701 of polymerase basic protein 2 (PB2) have been found frequently in the human H7N9 isolates but not in viruses isolated from avian species. We have recently identified a cluster of H7N9 viruses in ducks which circulated in China prior to the first recognition of zoonotic disease in 2013. These duck viruses have genetic background distinct from the zoonotic H7N9 lineage. We found that the introduction of PB2 mutation with K at 627 but not K at 591 or N at 701 to the duck H7N9 virus led to increased pathogenicity in mice. We also found that the induction of pro-inflammatory cytokines including TNF-α, IP-10, MCP-1 and MIP-1α were associated with increased severity of infection. We conclude that introduction of the mammalian adaptation mutations into the PB2 gene of duck H7N9 viruses, which are genetically unrelated to the zoonotic H7N9 lineage, can also enhance pathogenicity in mice.
Characterization of porcine simple sequence repeat variation on a population scale with genome resequencing data
Authors: Liu Congcong , Liu Yan , Zhang Xinyi , Xu Xuewen , Zhao Shuhong 
Published: May 2017

AbstractSimple sequence repeats (SSRs) are used as polymorphic molecular markers in many species. They contribute very important functional variations in a range of complex traits; however, little is known about the variation of most SSRs in pig populations. Here, using genome resequencing data, we identified ~0.63 million polymorphic SSR loci from more than 100 individuals. Through intensive analysis of this dataset, we found that the SSR motif composition, motif length, total length of alleles and distribution of alleles all contribute to SSR variability. Furthermore, we found that CG-containing SSRs displayed significantly lower polymorphism and higher cross-species conservation. With a rigorous filter procedure, we provided a catalogue of 16,527 high-quality polymorphic SSRs, which displayed reliable results for the analysis of phylogenetic relationships and provided valuable summary statistics for 30 individuals equally selected from eight local Chinese pig breeds, six commercial lean pig breeds and Chinese wild boars. In addition, from the high-quality polymorphic SSR catalogue, we identified four loci with potential loss-of-function alleles. Overall, these analyses provide a valuable catalogue of polymorphic SSRs to the existing pig genetic variation database, and we believe this catalogue could be used for future genome-wide genetic analysis.
Physiological concentrations of soluble uric acid are chondroprotective and anti-inflammatory
Authors: Lai Jenn-Haung , Luo Shue-Fen , Hung Li-Feng , Huang Chuan-Yueh , Lien Shiu-Bii , Lin Leou-Chyr , Liu Feng-Cheng , Yen B. Linju , Ho Ling-Jun 
Published: May 2017

AbstractHigh uric acid levels are a risk factor for cardiovascular disorders and gout; however, the role of physiological concentrations of soluble uric acid (sUA) is poorly understood. This study aimed to clarify the effects of sUA in joint inflammation. Both cell cultures of primary porcine chondrocytes and mice with collagen-induced arthritis (CIA) were examined. We showed that sUA inhibited TNF-α- and interleukin (IL)-1β–induced inducible nitric oxide synthase, cyclooxygenase-2 and matrix metalloproteinase (MMP)-13 expression. Examination of the mRNA expression of several MMPs and aggrecanases confirmed that sUA exerts chondroprotective effects by inhibiting the activity of many chondro-destructive enzymes. These effects attenuated collagen II loss in chondrocytes and reduced proteoglycan degradation in cartilage explants. These results were reproduced in chondrocytes cultured in three-dimensional (3-D) alginate beads. Molecular studies revealed that sUA inhibited the ERK/AP-1 signalling pathway, but not the IκBα-NF-κB signalling pathway. Increases in plasma uric acid levels facilitated by the provision of oxonic acid, a uricase inhibitor, to CIA mice exerted both anti-inflammatory and arthroprotective effects in these animals, as demonstrated by their arthritis severity scores and immunohistochemical analysis results. Our study demonstrated that physiological concentrations of sUA displayed anti-inflammatory and chondroprotective effects bothin vitroandin vivo.
Wing reduction influences male mating success but not female fitness in cockroaches
Authors: Kotyk Michael , Varadínová Zuzana 
Published: May 2017

AbstractAlthough cockroaches (Blattodea s. str.) exhibit high proportion of species with reduced wings, the underlying evolutionary forces remain unclear. Wing reduction in insects is generally considered advantageous for females and a trade-off between investment into the flying apparatus and reproduction is predicted to explain its evolution. However, what if the wing maintenance is an important issue for males’ fitness? Males raise wings during the ritualized courtship which is viewed as an unavoidable movement unveiling the tergal glands for female access. We, however, propose a novel male mating success hypothesis suggesting that male wings are essential for their successful mating. We tested these two competing, but not mutually exclusive hypotheses in the cockroach Eublaberus distanti. We found no effect of female wing loss on any of the measured fecundity characteristics despite that alatectomized females histolyzed flight muscles. On the contrary, alatectomized males did not histolyze wing muscles, but experienced a markedly decreased mating success. Our findings, therefore, provide the first evidence on the crucial mechanical role of wings on male mating success. Consequently, selection for the retention of wings in males rather than for their reduction in females can explain the evolution of sexual wing dimorphism in cockroaches and other insects.
Intravascular Ultrasound Guidance Improves the Long-term Prognosis in Patients with Unprotected Left Main Coronary Artery Disease Undergoing Percutaneous Coronary Intervention
Authors: Tian Jian , Guan Changdong , Wang Wenyao , Zhang Kuo , Chen Jue , Wu Yongjian , Yan Hongbing , Zhao Yanyan , Qiao Shubin , Yang Yuejin , Mintz Gary S. , Xu Bo , Tang Yida 
Published: May 2017

AbstractThis study compared the long term outcomes in patients with unprotected left main coronary artery (LMCA) disease who underwent stenting under the guidance of intravascular ultrasound (IVUS) or conventional angiography at a large single center. The primary outcome was the composite of all-cause death and myocardial infarction (MI) at 3 years. Target vessel revascularization (TVR) at 3 years was one of the secondary outcomes. Between January 2004 and December 2011, a total of 1,899 patients who underwent IVUS-guided (n = 713, 37.5%) or conventional angiography-guided (n = 1186, 62.5%) stenting were included. At 3 years, the unadjusted primary outcome trended lower in the IVUS-guided group versus the angiography-guided (6.9% vs. 8.4%, p = 0.22) although the TVR was similar between two groups (6.0% vs. 6.0%, p = 0.97). However, after adjustment for differences in baseline risk factors, IVUS-guidance was associated with significantly lower incidence of the composite of all-cause death and MI (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.50 to 0.84; p = 0.001), although there was still no significant difference in TVR between the two groups (HR: 1.09; 95% CI: 0.84 to 1.42; p = 0.53). IVUS guidance has benefits in improving the long-term prognosis for unprotected LMCA stenting.
More Than the Verbal Stimulus Matters: Visual Attention in Language Assessment for People With Aphasia Using Multiple-Choice Image Displays
Authors: Heuer Sabine , Ivanova Maria V. , Hallowell Brooke 
Published: May 2017

Purpose
Language comprehension in people with aphasia (PWA) is frequently evaluated using multiple-choice displays: PWA are asked to choose the image that best corresponds to the verbal stimulus in a display. When a nontarget image is selected, comprehension failure is assumed. However, stimulus-driven factors unrelated to linguistic comprehension may influence performance. In this study we explore the influence of physical image characteristics of multiple-choice image displays on visual attention allocation by PWA.

Method
Eye fixations of 41 PWA were recorded while they viewed 40 multiple-choice image sets presented with and without verbal stimuli. Within each display, 3 images (majority images) were the same and 1 (singleton image) differed in terms of 1 image characteristic. The mean proportion of fixation duration (PFD) allocated across majority images was compared against the PFD allocated to singleton images.

Results
PWA allocated significantly greater PFD to the singleton than to the majority images in both nonverbal and verbal conditions. Those with greater severity of comprehension deficits allocated greater PFD to nontarget singleton images in the verbal condition.

Conclusion
When using tasks that rely on multiple-choice displays and verbal stimuli, one cannot assume that verbal stimuli will override the effect of visual-stimulus characteristics.
3T‐2R non‐volatile TCAM with voltage limiter and self‐controlled bias circuit
Authors: Kim C. , Kwon K.‐W. 
Published: May 2017

A 3T‐2R non‐volatile ternary content‐addressable‐memory (nvTCAM) is proposed. Using a voltage limiter and self‐controlled bias circuit, both faster match line development and more sensing margin were possible when compared to the conventional nvTCAM. The voltage limiter provides a clear distinction between mismatch cell and ‘don't care’ cell. In case of nvTCAM made of non‐volatile memory (NVM) with a large resistance ratio, the sensing delay is reduced by 43.7% thanks to the combination of the self‐controlled bias circuit and voltage limiter. The proposed circuit works properly with NVM with resistance ratio as low as 3. The proposed nvTCAM cell was evaluated using a 65 nm CMOS process.