bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel FIKK kinase regulates the development of mosquito and liver stages of the malaria
Authors: Jaijyan Dabbu Kumar , Verma Praveen Kumar , Singh Agam Prasad 
Published: December 2016

AbstractProtein phosphorylation is the most important post-translational event in the regulation of various essential signaling pathways in a cell. Here, we show the functional characterization of a FIKK family protein kinase of the rodent malaria parasite (PbMLFK), which is expressed only in mosquito and liver stages and contains two functional C-terminal PEXEL motifs. We demonstrate that this protein plays a role in mosquito and liver stages of parasite growth. The oocysts of PbMLFK-deficient parasites produced 4-fold fewer sporozoites. In the liver of infected mice, PbMLFK-deficient parasites grew 100-fold less than did wild type parasites. We also show that the C-terminal domain of this protein has a functional serine-threonine kinase and that its activity was inhibited by a known PKA inhibitor. Transcriptome analysis of infected host cells suggests that in absence of this protein expression of the 288 host mRNAs are perturbed which are primarily associated with the immune system, cell cycle and metabolism.
High resolution 3D imaging of living cells with sub-optical wavelength phonons
Authors: Pérez-Cota Fernando , Smith Richard J. , Moradi Emilia , Marques Leonel , Webb Kevin F. , Clark Matt 
Published: December 2016

AbstractLabel-free imaging of living cells below the optical diffraction limit poses great challenges for optical microscopy. Biologically relevant structural information remains below the Rayleigh limit and beyond the reach of conventional microscopes. Super-resolution techniques are typically based on the non-linear and stochastic response of fluorescent labels which can be toxic and interfere with cell function. In this paper we present, for the first time, imaging of live cells using sub-optical wavelength phonons. The axial imaging resolution of our system is determined by the acoustic wavelength (λa = λprobe/2n) and not on the NA of the optics allowing sub-optical wavelength acoustic sectioning of samples using the time of flight. The transverse resolution is currently limited to the optical spot size. The contrast mechanism is significantly determined by the mechanical properties of the cells and requires no additional contrast agent, stain or label to image the cell structure. The ability to breach the optical diffraction limit to image living cells acoustically promises to bring a new suite of imaging technologies to bear in answering exigent questions in cell biology and biomedicine.
Anisotropic magnetic coupling with a two-dimensional characteristic in noncentrosymmetric Cr11Ge19
Authors: Han Hui , Zhang Lei , Zhu Xiangde , Du Haifeng , Ge Min , Ling Langsheng , Pi Li , Zhang Changjin , Zhang Yuheng 
Published: December 2016

AbstractIn this work, we successfully synthesize the single crystal Cr11Ge19. The magnetism of the noncentrosymmetric Cr11Ge19 with itinerant ferromagnetic ground state is thoroughly investigated on the single crystal. Based on the variation measurements including the angular rotation, temperature, and magnetic field dependence of magnetization, we find that this material exhibits strong magnetic anisotropy along the c-axis. To clearly reveal the magnetic interactions, the critical behavior is studied using the modified Arrott plot, the Kouvel-Fisher method, and the critical isotherm technique. Combining these different methods, three main critical exponents (β, γ, and δ) are obtained. The critical exponent β is close to the theoretical prediction of a three-dimensional XY model with spin-dimensionality n = 2, indicating two-dimensional magnetic coupling. Meanwhile, the critical exponent γ suggests that the magnetic interaction is of long-range type with magnetic exchange distance decaying as J(r) ≈ r−4.61. We propose that the ferromagnetic ground state of Cr11Ge19 is formed by the polarized magnetic moments along the c-axis, while the long-range magnetic coupling is established within the ab plane.
The XBP1 Arm of the Unfolded Protein Response Induces Fibrogenic Activity in Hepatic Stellate Cells Through Autophagy
Authors: Kim Rosa S. , Hasegawa Daisuke , Goossens Nicolas , Tsuchida Takuma , Athwal Varinder , Sun Xiaochen , Robinson Christopher L. , Bhattacharya Dipankar , Chou Hsin-I , Zhang David Y. , Fuchs Bryan C. , Lee Youngmin , Hoshida Yujin , Friedman Scott L. 
Published: December 2016

AbstractAutophagy and the unfolded protein response (UPR) both promote activation of hepatic stellate cells (HSC), however the link between the two stimuli remains unclear. Here we have explored the role of X-box binding protein 1 (XBP1), one of three UPR effector pathways and sought to establish the interdependence between autophagy and the UPR during HSC activation. XBP1 induction accompanied both culture-based HSC activation and ER stress induced by tunicamycin. Ectopic overexpression of XBP1 induced collagen 1-alpha expression in HSCs, which was inhibited by knockdown of ATG7, a critical autophagy mediator. Genome-wide transcriptomic profiling indicated an upregulation of collagen synthesis pathways, but not of the transforming growth factor (TGF)-b pathway, a canonical fibrogenic driver, suggesting that XBP1 activates a specific subset of fibrogenesis pathways independent of TGF-β1. XBP1 target gene signatures were significantly induced in rodent liver fibrosis models (n = 3–5) and in human samples of non-alcoholic fatty liver disease (NAFLD) (n = 72–135). Thus, XBP1-mediated UPR contributes to fibrogenic HSC activation and is functionally linked to cellular autophagy.
In vitro synthesis of a Major Facilitator Transporter for specific active transport across Droplet Interface Bilayers
Authors: Findlay Heather E. , Harris Nicola J. , Booth Paula J. 
Published: December 2016

AbstractNature encapsulates reactions within membrane-bound compartments, affording sequential and spatial control over biochemical reactions. Droplet Interface Bilayers are evolving into a valuable platform to mimic this key biological feature in artificial systems. A major issue is manipulating flow across synthetic bilayers. Droplet Interface Bilayers must be functionalised, with seminal work using membrane-inserting toxins, ion channels and pumps illustrating the potential. Specific transport of biomolecules, and notably transport against a concentration gradient, across these bilayers has yet to be demonstrated. Here, we successfully incorporate the archetypal Major Facilitator Superfamily transporter, lactose permease, into Droplet Interface Bilayers and demonstrate both passive and active, uphill transport. This paves the way for controllable transport of sugars, metabolites and other essential biomolecular substrates of this ubiquitous transporter superfamily in DIB networks. Furthermore, cell-free synthesis of lactose permease during DIB formation also results in active transport across the interface bilayer. This adds a specific disaccharide transporter to the small list of integral membrane proteins that can be synthesised via in vitro transcription/translation for applications of DIB-based artificial cell systems. The introduction of a means to promote specific transport of molecules across Droplet Interface Bilayers against a concentration gradient gives a new facet to droplet networks.
Mild intrauterine hypoperfusion reproduces neurodevelopmental disorders observed in prematurity
Authors: Ohshima Makiko , Coq Jacques-Olivier , Otani Kentaro , Hattori Yorito , Ogawa Yuko , Sato Yoshiaki , Harada-Shiba Mariko , Ihara Masafumi , Tsuji Masahiro 
Published: December 2016

AbstractSevere intrauterine ischemia is detrimental to the developing brain. The impact of mild intrauterine hypoperfusion on neurological development, however, is still unclear. We induced mild intrauterine hypoperfusion in rats on embryonic day 17 via arterial stenosis with metal microcoils wrapped around the uterine and ovarian arteries. All pups were born with significantly decreased birth weights. Decreased gray and white matter areas were observed without obvious tissue damage. Pups presented delayed newborn reflexes, muscle weakness, and altered spontaneous activity. The levels of proteins indicative of inflammation and stress in the vasculature, i.e., RANTES, vWF, VEGF, and adiponectin, were upregulated in the placenta. The levels of mRNA for proteins associated with axon and astrocyte development were downregulated in fetal brains. The present study demonstrates that even mild intrauterine hypoperfusion can alter neurological development, which mimics the clinical signs and symptoms of children with neurodevelopmental disorders born prematurely or with intrauterine growth restriction.
Localisation and origin of the bacteriochlorophyll-derived photosensitizer in the retina of the deep-sea dragon fish Malacosteus niger
Authors: Douglas Ronald H. , Genner Martin J. , Hudson Alan G. , Partridge Julian C. , Wagner Hans-Joachim 
Published: December 2016

AbstractMost deep-sea fish have a single visual pigment maximally sensitive at short wavelengths, approximately matching the spectrum of both downwelling sunlight and bioluminescence. However, Malcosteus niger produces far-red bioluminescence and its longwave retinal sensitivity is enhanced by red-shifted visual pigments, a longwave reflecting tapetum and, uniquely, a bacteriochlorophyll-derived photosensitizer. The origin of the photosensitizer, however, remains unclear. We investigated whether the bacteriochlorophyll was produced by endosymbiotic bacteria within unusual structures adjacent to the photoreceptors that had previously been described in this species. However, microscopy, elemental analysis and SYTOX green staining provided no evidence for such localised retinal bacteria, instead the photosensitizer was shown to be distributed throughout the retina. Furthermore, comparison of mRNA from the retina of Malacosteus to that of the closely related Pachystomias microdon (which does not contain a bacterichlorophyll-derived photosensitzer) revealed no genes of bacterial origin that were specifically up-regulated in Malacosteus. Instead up-regulated Malacosteus genes were associated with photosensitivity and may relate to its unique visual ecology and the chlorophyll-based visual system. We also suggest that the unusual longwave-reflecting, astaxanthin-based, tapetum of Malacosteus may protect the retina from the potential cytotoxicity of such a system.
The Angiogenic Secretome in VEGF overexpressing Breast Cancer Xenografts
Authors: Dore-Savard Louis , Lee Esak , Kakkad Samata , Popel Aleksander S. , Bhujwalla Zaver M. 
Published: December 2016

AbstractThe plasticity of cancer cells and the fluidity of the tumor microenvironment continue to present major challenges in the comprehensive understanding of cancer that is essential to design effective treatments. The tumor interstitial fluid (TIF) encompasses the secretome and holds the key to several of the phenotypic characteristics of cancer. Difficulties in sampling this fluid have resulted in limited characterization of its components. Here we have sampled TIF from triple negative and estrogen receptor (ER)-positive human breast tumor xenografts with or without VEGF overexpression. Angiogenesis-related factors were characterized in the TIF and plasma, to understand the relationship between the TIF and plasma secretomes. Clear differences were observed between the TIF and plasma angiogenic secretomes in triple negative MDA-MB-231 breast cancer xenografts compared to ER-positive MCF-7 xenografts with or without VEGF overexpression that provide new insights into TIF components and the role of VEGF in modifying the angiogenic secretome.
A Biomimetic Silk Fibroin/Sodium Alginate Composite Scaffold for Soft Tissue Engineering
Authors: Wang Yiyu , Wang Xinyu , Shi Jian , Zhu Rong , Zhang Junhua , Zhang Zongrui , Ma Daiwei , Hou Yuanjing , Lin Fei , Yang Jing , Mizuno Mamoru 
Published: December 2016

AbstractA cytocompatible porous scaffold mimicking the properties of extracellular matrices (ECMs) has great potential in promoting cellular attachment and proliferation for tissue regeneration. A biomimetic scaffold was prepared using silk fibroin (SF)/sodium alginate (SA) in which regular and uniform pore morphology can be formed through a facile freeze-dried method. The scanning electron microscopy (SEM) studies showed the presence of interconnected pores, mostly spread over the entire scaffold with pore diameter around 54~532 μm and porosity 66~94%. With significantly better water stability and high swelling ratios, the blend scaffolds crosslinked by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) provided sufficient time for the formation of neo-tissue and ECMs during tissue regeneration. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) results confirmed random coil structure and silk I conformation were maintained in the blend scaffolds. What’s more, FI-TR spectra demonstrated crosslinking reactions occurred actually among EDC, SF and SA macromolecules, which kept integrity of the scaffolds under physiological environment. The suitable pore structure and improved equilibrium swelling capacity of this scaffold could imitate biochemical cues of natural skin ECMs for guiding spatial organization and proliferation of cells in vitro, indicating its potential candidate material for soft tissue engineering.
Leptospira surface adhesin (Lsa21) induces Toll like receptor 2 and 4 mediated inflammatory responses in macrophages
Authors: Faisal Syed M. , Varma Vivek P. , Subathra M. , Azam Sarwar , Sunkara Anil K. , Akif Mohd , Baig Mirza. S. , Chang Yung-Fu 
Published: December 2016

AbstractLeptospirosis is zoonotic and emerging infectious disease of global importance. Little is understood about Leptospira pathogenesis and host immune response. In the present work we have investigated how Leptospira modulates the host innate immune response mediated by Toll-like receptors (TLRs) via surface exposed proteins. We screened Leptospira outer membrane/surface proteins for their ability to activate/inhibit TLR2/4 signaling in HEK293 cell lines. Of these the 21 kDa Leptospira surface adhesin, Lsa21 had strong TLR2 and TLR4 activity leading to production of proinflammatory cytokines and expression of costimulatory molecules in mouse macrophages. This activity of Lsa21 on innate response was dependent on activation of mitogen activated protein kinases (MAPKs) via stimulating the rapid phosphorylation of p38, JNK and activation of transcription factor NF-κB. Additionally, neutralizing antibodies against TLR2 and TLR4 significantly inhibited cytokine secretion and attenuated Lsa21 induced phosphorylation of p38 and JNK. Furthermore, Lsa21 induced cytokine levels were significantly lower in TLR2−/− and TLR4−/− than in wild type mouse macrophage cell lines. Confocal microscopy and molecular docking confirmed that Lsa21 interacted with both TLR2 and TLR4. These results indicate that Lsa21 is a potent TLR2 and TLR4 agonist that induces strong innate response and may play important role in Leptospira pathogenesis.
Metabolic engineering of Corynebacterium crenatium for enhancing production of higher alcohols
Authors: Su Haifeng , Lin Jiafu , Wang GuangWei 
Published: December 2016

AbstractBiosynthesis approaches for the production of higher alcohols as a source of alternative fossil fuels have garnered increasing interest recently. However, there is little information available in the literature about using undirected whole-cell mutagenesis (UWCM) in vivo to improve higher alcohols production. In this study, for the first time, we approached this question from two aspects: first preferentially improving the capacity of expression host, and subsequently optimizing metabolic pathways using multiple genetic mutations to shift metabolic flux toward the biosynthetic pathway of target products to convert intermediate 2-keto acid compounds into diversified C4~C5 higher alcohols using UWCM in vivo, with the aim of improving the production. The results demonstrated the production of higher alcohols including isobutanol, 2-methyl-1-butanol, 3-methyl-1-butanol from glucose and duckweed under simultaneous saccharification and fermentation (SSF) scheme were higher based on the two aspects compared with only the use of wild-type stain as expression host. These findings showed that the improvement via UWCM in vivo in the two aspects for expression host and metabolic flux can facilitate the increase of higher alcohols production before using gene editing technology. Our work demonstrates that a multi-faceted approach for the engineering of novel synthetic pathways in microorganisms for improving biofuel production is feasible.
Loss of miR-140 is a key risk factor for radiation-induced lung fibrosis through reprogramming fibroblasts and macrophages
Authors: Duru Nadire , Zhang Yongshu , Gernapudi Ramkishore , Wolfson Benjamin , Lo Pang-Kuo , Yao Yuan , Zhou Qun 
Published: December 2016

AbstractRadiation-induced lung fibrosis (RILF) is a common side effect for patients with thoracic cancer receiving radiation therapy. RILF is characterized by excessive collagen deposition mediated by TGF-β1 and its downstream factor SMAD3, but the exact molecular mechanism leading to fibrosis is yet to be determined. The present study investigated the impact of miR-140 on RILF development. Herein, we first found that loss of miR-140 is a marker of fibrotic lung tissuein vivoone-year post-radiation treatment. We showed that miR-140 knockout primary lung fibroblasts have a higher percentage of myofibroblasts compared to wild type primary lung fibroblasts, and that loss of miR-140 expression leads to increased activation of TGF-β1 signaling as well as increased myofibroblast differentiation. We also identified fibronectin as a novel miR-140 target gene in lung fibroblasts. Finally, we have shown that miR-140 deficiency promotes accumulation of M2 macrophages in irradiated lung tissues. These data suggest that miR-140 is a key protective molecule against RILF through inhibiting myofibroblast differentiation and inflammation.
Counteracting bone fragility with human amniotic mesenchymal stem cells
Authors: Ranzoni Anna M. , Corcelli Michelangelo , Hau Kwan-Leong , Kerns Jemma G. , Vanleene Maximilien , Shefelbine Sandra , Jones Gemma N. , Moschidou Dafni , Dala-Ali Benan , Goodship Allen E. , De Coppi Paolo , Arnett Timothy R. , Guillot Pascale V. 
Published: December 2016

AbstractThe impaired maturation of bone-forming osteoblasts results in reduced bone formation and subsequent bone weakening, which leads to a number of conditions such as osteogenesis imperfecta (OI). Transplantation of human fetal mesenchymal stem cells has been proposed as skeletal anabolic therapy to enhance bone formation, but the mechanisms underlying the contribution of the donor cells to bone health are poorly understood and require further elucidation. Here, we show that intraperitoneal injection of human amniotic mesenchymal stem cells (AFSCs) into a mouse model of OI (oim mice) reduced fracture susceptibility, increased bone strength, improved bone quality and micro-architecture, normalised bone remodelling and reduced TNFα and TGFβ sigalling. Donor cells engrafted into bones and differentiated into osteoblasts but importantly, also promoted endogenous osteogenesis and the maturation of resident osteoblasts. Together, these findings identify AFSC transplantation as a countermeasure to bone fragility. These data have wider implications for bone health and fracture reduction.
Use of tDCS in Aphasia Rehabilitation: A Systematic Review of the Behavioral Interventions Implemented With Noninvasive Brain Stimulation for Language Recovery
Authors: Galletta Elizabeth E. , Conner Peggy , Vogel-Eyny Amy , Marangolo Paola 
Published: December 2016

PurposeThe purpose of this article is to review the behavioral treatments used in aphasia rehabilitation research that have been combined with transcranial direct current stimulation (tDCS). Although tDCS in aphasia treatment has shown promise, the results have not been conclusive, and their interpretation is further compounded by the heterogeneity of study characteristics. Because implementing a behavioral task during brain stimulation has been shown to be pivotal to the adjuvant effects of tDCS, we analyze the behavioral treatments that have been paired with tDCS.MethodA computerized database search (PubMed) was completed to document and review aphasia treatment studies that combine behavioral treatment with noninvasive brain stimulation in the form of tDCS. Two authors reviewed each aphasia tDCS article published between 2008 and 2015 and evaluated (a) the behavioral interventions for aphasia that have been combined with tDCS, and (b) the methodological variables that may have influenced language outcomes in the tDCS aphasia literature.ConclusionsA review of the behavioral treatments implemented in tDCS aphasia rehabilitation studies highlights several methodological considerations for future investigations. Impairment-focused and pragmatic treatments have been implemented in tDCS aphasia research studies. No one behavioral approach stands out as the best treatment to combine with tDCS for the promotion of language recovery.
Self-Judgments of Word Production Accuracy in Acquired Apraxia of Speech
Authors: Wambaugh Julie , Shuster Linda , Bailey Dallin J. , Mauszycki Shannon , Kean Jacob , Nessler Christina , Wright Sandra , Brunsvold Jessica 
Published: December 2016

Purpose
The ability to recognize one's own speech errors has long been considered a clinical feature of acquired apraxia of speech (AOS) despite limited empirical data supporting this notion. This study was designed to (a) investigate the ability of speakers with AOS to self-judge the accuracy of their own word productions and (b) examine the test–retest stability of a measure to quantify the self-judgments of speakers with AOS.

Method
Twenty-four speakers with AOS and aphasia repeated mono- and multisyllabic words. After each word, they indicated whether their production was correct or incorrect. This procedure was repeated 1 week later to examine performance stability.

Results
Percentage of incorrect word productions was stable for the group across times. Accuracy of judgments ranged from 64% to 100% at Time 1 and from 56% to 100% at Time 2. Inaccurate judgments of error productions (false positives) occurred much more frequently than inaccurate judgments of correct productions (false negatives).

Conclusions
Error production was remarkably stable in our participants. As a group, the participants failed to detect almost one third of words produced erroneously. However, accuracy and stability of judgments over sampling times varied across participants. Findings suggest that error awareness might be a worthwhile target for treatment in some individuals with AOS.

Supplemental Material

https://doi.org/10.23641/asha.14963550