bluuebunny/crossref_metadata_2025 huggingface dataset:
Enantioselective Inhibition of Human Papillomavirus L1 Pentamer Formation by Chiral‐Proline Modified Calix[4]arenes: Targeting the Protein Interface
Authors: Fu Ding‐Yi , Lu Tong , Liu Yu‐Xue , Li Fei , Ogden Mark I. , Wang Ye , Wu Yuqing , Mocerino Mauro
Published: December 2016

Although current human papillomavirus (HPV) vaccines can protect well against infection, they are effective only for a limited number of subtypes. Coupled with the dilemma that no efficient prescription is currently clinically available for therapy, there is an urgent need to develop new anti‐HPV agents. In the present study l‐ and d‐Proline modified calix[4]arenes (Pro‐C4 A) were investigated to determine any differences in their effect on the assembly of HPV 16 L1 pentamer (L1‐p). The mechanism of action using model peptides was investigated by Matrix‐Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI‐TOF‐MS) and Nuclear Magnetic Resonance (NMR) and revealed that the binding was targeting the basic residues at L1 interface. This was also well supported by the trypsin digestion experiments and molecular simulations performed on the full‐length L1. The large energy and morphology differences revealed by molecular simulations explain the binding disparity of l‐ and d‐Pro‐C4 A to L1, and consequently the selective inhibition of them on L1‐p formation. The present study opens a way to develop enantioselective and cost‐effective inhibitors for L1‐p formation, which might be used as a new kind of anti‐HPV agent and could be extended to other viruses based on similar mechanisms.
Copper‐Promoted Direct C‐H Aminationof Benzothiazoles Using Formamides as Nitrogen Sources: An Efficient Approach for Synthesis of 2‐Aminothiazoles
Authors: Yu Mengxuan , Wang Biying , Zhou Peng , Jia Xiaodong , Yuan Yu
Published: December 2016

An efficient, practical and convenient process based on copper‐promoted decarboxylative coupling between benzothiazoles with formamides was that providing a series of 2‐aminobenzothiazoles in high yields.
Transparent Nanofibrous Mesh Self‐Assembled from Molecular LEGOs for High Efficiency Air Filtration with New Functionalities
Authors: Singh Varun Kumar , Ravi Sai Kishore , Sun Wanxin , Tan Swee Ching
Published: December 2016

Alarming levels of particulate matter pollution in air pose a serious health threat in several countries, therefore intriguing a strong need for an economic and a viable technology of air filtration. Current air purification technology is rather expensive with certain types even having the risk of emitting hazardous by‐products. The authors have developed a multifunctional air filter inspired from the nasal hairs possessing an ability to specifically trap/exhale the foreign particles and allergens while still letting the air flow. This design is achieved by introducing different functionalities at different dimensional scale employing a bottom‐up approach starting with an organic molecule which is further self‐organized to form nanoparticles and ultimately to a nanofibrous mesh. While the molecular building block inherently possesses the property of shielding Ultraviolet (UV) rays, the nanofibrous mesh built up from it aids in trapping the particulate matter while maintaining good air flow. By controlling the concentration of the organic molecule, the formation of fibers has been enabled in the nanoscale regime to obtain high particle‐capture possibilities. The self‐assembled nanofibrous filter thus designed has achieved a high filtration efficiency of ≈90% for the PM 2.5 particle in congruence with the ability to block the harmful UV radiations.
Enhancement of Upconverted Fluorescence by Interference Layers
Authors: Wirth Janina , Green Kory K. , O'Connor Megan , Lim Shuang F.
Published: December 2016

Upconverting nanoparticles show potential applications in the field of photovoltaics and array‐based detection devices. While fluorescence enhancement using interference of incident radiation is well known in Stokes‐shift type systems such as fluorescent dyes; the effect of such interference geometry in nonlinear Anti‐Stokes type emission, such as in upconversion rare earth photophysics is demonstrated for the first time. This work describes in detail the influence of the interference modulation on both the excitation (interion energy transfer) and radiative decay with nonradiative decay processes active between emissive levels. These effects are illustrated in the thickness dependence of the decay rate and rise time. Single particle upconverted spectra and time‐resolved measurements show concurrent optimization of the infrared absorption and emission at 540 and 650 nm, with an average enhanced emission of 20 times at λ = 540 and 45 times at λ = 650 nm, dependent on the interference layer thickness and on the excitation intensity. The experimental results are correlated with finite element modeling. Both experiments and calculations show emission enhancement at an interference layer thickness of about 740 ± 20 nm, where such tolerance and the planar design, leads to ease in implementation in applications.
Modified mRNA as a therapeutic tool to induce cardiac regeneration in ischemic heart disease
Authors: Hadas Yoav , Katz Michael G. , Bridges Charles R. , Zangi Lior
Published: December 2016

Ischemic heart disease (IHD) is a leading cause of morbidity and mortality in developed countries. Current pharmacological and interventional therapies provide significant improvement in the life quality of patient; however, they are mostly symptom‐oriented and not curative. A high disease and economic burden of IHD requires the search for new therapeutic strategies to significantly improve patients’ prognosis and quality of life. One of the main challenges during IHD is the massive loss of cardiomyocytes that possess minimal regenerative capacity. Recent understanding of the pathophysiological mechanisms underlying IHD, as well as new therapeutic approaches provide new hope for patients suffering from IHD. Synthetic modified mRNA (modRNA) is a new gene delivery vector that is increasingly used in in vivo applications. modRNA is a relatively stable, non‐immunogenic, highly‐expressed molecule that has been shown to mediate high and transient expression of proteins in different type of cells and tissues including cardiomyocytes. modRNA properties, together with its expression kinetics in the heart make it an attractive option for the treatment of IHD, especially after myocardial infarction. In this review we discuss the role of gene therapy in cardiac regeneration as an approach to treat IHD; traditional and innovative gene delivery methods; and focus specifically on modRNA structure, mode of delivery, and its use for the induction of endogenous regenerative capacity, mainly in the context of IHD. WIREs Syst Biol Med 2017, 9:e1367. doi: 10.1002/wsbm.1367

This article is categorized under:

Developmental Biology > Stem Cell Biology and Regeneration

Translational, Genomic, and Systems Medicine > Therapeutic Methods

Translational, Genomic, and Systems Medicine > Translational Medicine
[Si4]4– and [Si9]4– Clusters Crystallized from Liquid Ammonia Solution – Synthesis and Characterization of K8[Si4][Si9]·(NH3)14.6
Authors: Benda Christian B. , Henneberger Thomas , Klein Wilhelm , Fässler Thomas F.
Published: December 2016

The extraction of the silicide K12Si17 with liquid ammonia in the presence of a sequestering agent and AuPPh3Cl or Zn(Cp*)2 led to crystals of the solvate compound K8[Si4][Si9]·(NH3)14.6, which was characterized by single‐crystal X‐ray diffraction. It is the first compound with an isolated and ligand‐free [Si4]4– cluster obtained from solution. It also contains one [Si9]4– cluster per formula unit, whereas the precursor K12Si17 is built from [Si4]4– and [Si9]4– clusters with a 2:1 ratio.
Method of Evaluating Delayed Fracture Susceptibility of Tempered Martensitic Steel Showing Quasi-Cleavage Fracture
Authors: Matsumoto Yu , Takai Kenichi
Published: December 2016

The difference in the hydrogen charging methods, immersion in a NH4SCN aqueous solution, and cathodic electrolysis in a NaOH aqueous solution, did not affect the hydrogen state present in the steel, but it did affect the surface state of the specimens through corrosion, causing fracture strength to fluctuate in tensile testes. As for stress application method, the fracture strength at lower crosshead speeds in tensile tests was consistent with that found for hydrogen precharging prior to stress application in CLTs as long as hydrogen charging was conducted by cathodic electrolysis. However, the fracture strength obtained with concurrent hydrogen charging without precharging prior to stress application in CLTs was higher than that with hydrogen precharging prior to stress application in CLTs regardless of the same hydrogen content. In other words, delayed fracture susceptibility was affected by the order of hydrogen charging and stress application for quasi-cleavage fracture associated with local plastic deformation, i.e., dislocation motion. Therefore, by taking into account the cathodic electrolysis in the NaOH solution, the low crosshead speed and the order of hydrogen charging and stress application, the fracture strength in CLTs, and tensile tests coincided with respect to quasi-cleavage fracture even though the stress application methods were different.
Identification of Oxidized Phosphatidylinositols Present in OxLDL and Human Atherosclerotic Plaque
Authors: Hasanally Devin , Edel Andrea , Chaudhary Rakesh , Ravandi Amir
Published: December 2016

Oxidized low‐density lipoprotein (OxLDL) plays an important role in initiation and progression of atherosclerosis. Proatherogenic effects of OxLDL have been attributed to bioactive phospholipids generated during LDL oxidation. It is unknown what effect oxidation has on the phosphatidylinositol (PtdIns) molecules in LDL, even though PtdIns is 6% of the total LDL phospholipid pool. We sought to identify and quantitate oxidized phosphatidylinositol (OxPtdIns) species in OxLDL and human atherosclerotic plaque. Bovine liver PtdIns was subjected to non‐enzymatic and lipoxygenase‐catalyzed oxidation. Reversed‐phase liquid chromatography with negative ESI–MS identified and confirmed compounds by fragmentation pattern analysis from which an OxPtdIns library was generated. Twenty‐three OxPtdIns molecules were identified in copper‐oxidized human LDL at 0, 6, 12, 24, 30, and 48 h, and in human atherosclerotic plaque. In OxLDL, OxPtdIns species containing aldehydes and carboxylates comprised 17.3 ± 0.1 and 0.9 ± 0.2%, respectively, of total OxPtdIns in OxLDL at 48 h. Hydroperoxides and isoprostanes at 24 h (68.5 ± 0.2 and 22.8 ± 0.2%) were significantly greater than 12 h (P < 0.01) without additional changes thereafter. Hydroxides decreased with increased oxidation achieving a minimum at 24 h (5.2 ± 0.3%). Human atherosclerotic plaques contained OxPtdIns species including aldehydes, carboxylates, hydroxides, hydroperoxides and isoprostanes, comprising 18.6 ± 4.7, 1.5 ± 0.7, 16.5 ± 7.4, 33.3 ± 1.1 and 30.2 ± 3.3% of total OxPtdIns compounds. This is the first identification of OxPtdIns molecules in human OxLDL and atherosclerotic plaque. With these novel molecules identified we can now investigate their potential role in atherosclerosis.
The role of guided growth as it relates to limb lengthening
Authors: Stevens Peter M.
Published: December 2016

For decades, the classic indication for limb lengthening has been reserved for anisomelia that was expected to reach or exceed 5 cm at maturity. Epiphysiodesis was reserved for discrepancies in the 2–5 cm range. With the increasing sophistication of fixators, including rail, hexapod, and hybrid, complex deformities may be corrected simultaneously while moderate to extreme lengthening is achieved. More recently, iterations of telescoping intramedullary rods have further strengthened our armamentarium. Meanwhile, permanent epiphysiodesis techniques, both open and percutaneous, have yielded to more versatile and reversible tethering of one (angle) or both (length) sides of a physis. While the techniques of guided growth and callotasis seem to be diametrically opposed, they may be used in a tandem or complementary fashion, for the benefit of the patient. If treatment is undertaken during skeletal growth, one must be aware that issues remain regarding the accurate assessment of skeletal maturity and prediction of the ultimate outcome. Therefore, there is potential for over- or undercorrection. Reversible and serial guided growth now enable the surgeon to commence intervention at a comparatively young age, for the purpose of optimizing limb alignment and reducing the ultimate discrepancy. Frame application may be delayed or, in some cases, avoided altogether. With the limb properly aligned at the outset of lengthening, elective use of a telescoping intramedullary nail may now be favored over a frame accordingly.
The application of retinal fundus camera imaging in dementia: A systematic review
Authors: McGrory Sarah , Cameron James R. , Pellegrini Enrico , Warren Claire , Doubal Fergus N. , Deary Ian J. , Dhillon Baljean , Wardlaw Joanna M. , Trucco Emanuele , MacGillivray Thomas J.
Published: December 2016

Introduction

The ease of imaging the retinal vasculature, and the evolving evidence suggesting this microvascular bed might reflect the cerebral microvasculature, presents an opportunity to investigate cerebrovascular disease and the contribution of microvascular disease to dementia with fundus camera imaging.

Methods

A systematic review and meta‐analysis was carried out to assess the measurement of retinal properties in dementia using fundus imaging.

Results

Ten studies assessing retinal properties in dementia were included. Quantitative measurement revealed significant yet inconsistent pathologic changes in vessel caliber, tortuosity, and fractal dimension. Retinopathy was more prevalent in dementia. No association of age‐related macular degeneration with dementia was reported.

Discussion

Inconsistent findings across studies provide tentative support for the application of fundus camera imaging as a means of identifying changes associated with dementia. The potential of fundus image analysis in differentiating between dementia subtypes should be investigated using larger well‐characterized samples. Future work should focus on refining and standardizing methods and measurements.
Higher severity of cocaine addiction is associated with tactile and somatic hallucinations
Authors: Roncero C. , Grau-López L. , Palma-Álvarez R.F. , Rodriguez-Cintas L. , Ros-Cucurull E. , Esojo A. , Daigre C.
Published: December 2016

Background

The aim of this study is to describe the features of cocaine-dependent patients who have had cocaine-induced tactile/somatic hallucinations (CITSH), and to analyze the association with addiction-related variables and psychiatric comorbidity, comparing patients with CITSH, patients with cocaine psychotic symptoms (CIP) and no CITSH, and patients without any psychotic symptom.

Method

A cross-sectional study was conducted in 767 cocaine-dependent patients in an outpatient treatment center for addictions. The following data were obtained: sociodemographic characteristics, CIP information, addiction-related variables and psychiatric comorbidity. A bivariate and multivariate analysis was performed.

Results

Of the whole sample, 6.6% reported CITSH at some point of their lives, 48.4% had suffered some CIP other than CITSH, and 45% had not experienced any psychotic symptom. According to multivariate analysis, risk of overdose increases by 12.1 (OR) times the probability of having had CITSH compared patients with CIP-no-CITSH. Other variables associated to patients with CITSH were: age of drug use onset, presence of episodes of overdose, prevalence of psychotic disorder induced by cocaine. In general, in all variables studied, patients with CITSH presented worse clinical features (addiction variables and psychiatric comorbidity) than patients with CIP without CITSH and non-CIP group.

Conclusion

CITSH are usually associated with other psychotic symptoms induced by cocaine. The patients who experienced CITSH are more severe cases compared both with patients with CIP without CITSH and patients without CIP. Increased risk of overdose is an important issue in this type of patients.
The “Begram Ivories”: A Successful Case of Restitution of Some Antiquities Stolen from the National Museum of Afghanistan in Kabul
Authors: Simpson John
Published: December 2016

This article details a successful case of restitution of important antiquities stolen from the National Museum of Afghanistan in Kabul during the Afghan Civil War (1992–94). These items had been excavated by the Délégation Archéologique Française en Afghanistan at the site of Begram during 1937 and 1939 and were allocated to the museum in Kabul when the excavated finds were divided between the National Museum of Afghanistan and the Musée Guimet (Paris). In Kabul, the most important objects were put on permanent display, but they were placed in storage in 1989 when the museum was officially closed and the capital threatened by war after the withdrawal of Soviet forces. Many objects were hidden, and some are now touring in an international exhibition hosted by the British Museum in 2011.1However, most of the Begram ivories were stolen and entered different collections. The following article discusses how a group of 20 of these exquisite carvings were acquired, conserved, exhibited, and returned to Kabul as a direct result of the negotiations for the British Museum exhibition.2This allowed the first scientific analyses of Indian ivories of this period, and the results provided important new evidence for the extent of polychromy as well as the scale of the different unrecorded conservation treatments previously applied to these highly fragile objects.3The objects were returned safely to Kabul in 2012. This article also sets out some of the lessons learned from this chain of events and how it can provide an example for future restitutions.
Putting into Place Solutions for Nazi Era Dispossessions of Cultural Objects: The UK Experience
Authors: Woodhead Charlotte
Published: December 2016

Since 2000, the United Kingdom’s Spoliation Advisory Panel has provided an alternative dispute resolution mechanism for resolving disputes surrounding Nazi era dispossessions of cultural objects. This article analyzes the way in which the panel has reached its recommendations and how they have been implemented. While the panel’s recommendations provide a means of resolving disputes in circumstances where litigation might fail a claimant, claimants may encounter difficulties should an institution fail to implement the recommended remedy because of the extra-judicial nature of the recommendations. This article therefore analyzes the effectiveness of the panel’s work in overcoming some of the shortcomings of litigation and the way in which the parties have put into effect the panel’s recommendations. Furthermore, suggestions are made for ways in which to ensure compliance with the recommendations even in the absence of judicial enforcement.
False Closure? Known Unknowns in Repatriated Antiquities Cases
Authors: Tsirogiannis Christos
Published: December 2016

Based on research into the confiscated photographic and document archives in the hands of the top antiquities dealers (Robin Symes-Christos Michaelides, Robert Hecht, Giacomo Medici, and Gianfranco Becchina), so far more than 250 looted and smuggled masterpieces have been repatriated from the most reputable North American museums, private collections, and galleries, mainly to the Italian and the Greek states. Most of these repatriations were advertised in the press as voluntary action by the institutions and the individuals who possessed them. However, this is far from true; the repatriations were the results of lengthy negotiations, where the presentation of evidence alternated with diplomatic tactics and legal threats in order for the two parties (in some cases, three) to reach an agreement. Among the much-celebrated repatriated antiquities are at least two cases that require further research regarding their legal owner. This article aims to analyze these two cases and to set out new questions. In the end, there is doubt that the state who finally received these antiquities is necessarily the one from which they have been looted and smuggled. Based on this analysis, the article aims to highlight alternative paths to the discovery of the truth, paths that might have been more effective, if they had been followed.
Bronchoskopie in therapeutischer Mission – interventionelle Bronchologie
Authors: Franzen Daniel , Schneiter Didier , Freitag Lutz
Published: December 2016

Zusammenfassung. Die interventionelle Bronchologie ist eine verhältnismässig junge Subspezialisierung der Pneumologie und Thoraxchirurgie. Die Bronchoskopie hat sich in der Vergangenheit vor allem auf die Diagnostik von pulmonalen Infektionen und Malignomen beschränkt. Durch ein ständig wachsendes Armamentarium an therapeutischen Möglichkeiten wachsen jedoch die Indikationen für endobronchiale Eingriffe zusehends. Das heutige Arsenal an therapeutischen Möglichkeiten der interventionellen Bronchologie wird in diesem Artikel vorgestellt.
Increased Depth, Impact, and Sustainability: Eos Magazine Goes Monthly
Authors: McEntee Chris
Published: December 2016

This shift means that the magazine will be more substantial, with an increase in each issue’s page count to offer more features and in-depth reporting.
Molecular imaging with engineered physiology
Authors: Desai Mitul , Slusarczyk Adrian L. , Chapin Ashley , Barch Mariya , Jasanoff Alan
Published: December 2016

In vivo imaging techniques are powerful tools for evaluating biological systems. Relating image signals to precise molecular phenomena can be challenging, however, due to limitations of the existing optical, magnetic and radioactive imaging probe mechanisms. Here we demonstrate a concept for molecular imaging which bypasses the need for conventional imaging agents by perturbing the endogenous multimodal contrast provided by the vasculature. Variants of the calcitonin gene-related peptide artificially activate vasodilation pathways in rat brain and induce contrast changes that are readily measured by optical and magnetic resonance imaging. CGRP-based agents induce effects at nanomolar concentrations in deep tissue and can be engineered into switchable analyte-dependent forms and genetically encoded reporters suitable for molecular imaging or cell tracking. Such artificially engineered physiological changes, therefore, provide a highly versatile means for sensitive analysis of molecular events in living organisms.
Kaleidoscopic imaging patterns of complex structures fabricated by laser-induced deformation
Authors: Zhang Haoran , Yang Fengyou , Dong Jianjie , Du Lena , Wang Chuang , Zhang Jianming , Guo Chuan Fei , Liu Qian
Published: December 2016

Complex surface structures have stimulated a great deal of interests due to many potential applications in surface devices. However, in the fabrication of complex surface micro-/nanostructures, there are always great challenges in precise design, or good controllability, or low cost, or high throughput. Here, we present a route for the accurate design and highly controllable fabrication of surface quasi-three-dimensional (quasi-3D) structures based on a thermal deformation of simple two-dimensional laser-induced patterns. A complex quasi-3D structure, coaxially nested convex–concave microlens array, as an example, demonstrates our capability of design and fabrication of surface elements with this method. Moreover, by using only one relief mask with the convex–concave microlens structure, we have gotten hundreds of target patterns at different imaging planes, offering a cost-effective solution for mass production in lithography and imprinting, and portending a paradigm in quasi-3D manufacturing.
Autonomy in materials research: a case study in carbon nanotube growth
Authors: Nikolaev Pavel , Hooper Daylond , Webber Frederick , Rao Rahul , Decker Kevin , Krein Michael , Poleski Jason , Barto Rick , Maruyama Benji
Published: December 2016

Advances in materials are an important contributor to our technological progress, and yet the process of materials discovery and development itself is slow. Our current research process is human-centred, where human researchers design, conduct, analyse and interpret experiments, and then decide what to do next. We have built an Autonomous Research System (ARES)—an autonomous research robot capable of first-of-its-kind closed-loop iterative materials experimentation. ARES exploits advances in autonomous robotics, artificial intelligence, data sciences, and high-throughput and in situ techniques, and is able to design, execute and analyse its own experiments orders of magnitude faster than current research methods. We applied ARES to study the synthesis of single-walled carbon nanotubes, and show that it successfully learned to grow them at targeted growth rates. ARES has broad implications for the future roles of humans and autonomous research robots, and for human-machine partnering. We believe autonomous research robots like ARES constitute a disruptive advance in our ability to understand and develop complex materials at an unprecedented rate.
The competing mini-dumbbell mechanism: new insights into CCTG repeat expansion
Authors: Guo Pei , Lam Sik Lok
Published: December 2016

CCTG repeat expansions in intron 1 of the cellular nucleic acid-binding protein gene are associated with myotonic dystrophy type 2. Recently, we have reported a novel mini-dumbbell (MDB) structure formed by two CCTG or TTTA repeats, which potentially has a critical role in repeat expansions. Here we present a mechanism, called the competing MDB mechanism, to explain how the formation of MDB can lead to efficient mismatch repair (MMR) escape and thus CCTG repeat expansions during DNA replication. In a long tract of CCTG repeats, two competing MDBs can be formed in any segment of three repeats. Fast exchange between these MDBs will make the commonly occupied repeat behave like a mini-loop. Further participations of the 5′- or 3′-flanking repeat in forming competing MDBs will make the mini-loop shift in the 5′- or 3′-direction, thereby providing a pathway for the mini-loop to escape from MMR. To avoid the complications due to the formation of hairpin conformers in longer CCTG repeats, we made use of TTTA repeats as model sequences to demonstrate the formation of competing MDBs and shifting of mini-loop in a long tract of repeating sequence.
Multiparameter mechanical and morphometric screening of cells
Authors: Masaeli Mahdokht , Gupta Dewal , O’Byrne Sean , Tse Henry T. K. , Gossett Daniel R. , Tseng Peter , Utada Andrew S. , Jung Hea-Jin , Young Stephen , Clark Amander T. , Di Carlo Dino
Published: December 2016

We introduce a label-free method to rapidly phenotype and classify cells purely based on physical properties. We extract 15 biophysical parameters from cells as they deform in a microfluidic stretching flow field via high-speed microscopy and apply machine-learning approaches to discriminate different cell types and states. When employing the full 15 dimensional dataset, the technique robustly classifies individual cells based on their pluripotency, with accuracy above 95%. Rheological and morphological properties of cells while deforming were critical for this classification. We also show the application of this method in accurate classifying cells based on their viability, drug screening and detecting populations of malignant cells in mixed samples. We show that some of the extracted parameters are not linearly independent, and in fact we reach maximum classification accuracy by using only a subset of parameters. However, the informative subsets could vary depending on cell types in the sample. This work shows the utility of an assay purely based on intrinsic biophysical properties of cells to identify changes in cell state. In addition to a label-free alternative to flow cytometry in certain applications, this work, also can provide novel intracellular metrics that would not be feasible with labeled approaches (i.e. flow cytometry).
Conditional knockout of N-WASP in mouse fibroblast caused keratinocyte hyper proliferation and enhanced wound closure
Authors: Jain Neeraj , Kalailingam Pazhanichamy , Tan Kai Wei , Tan Hui Bing , Sng Ming Keat , Chan Jeremy Soon Kiat , Tan Nguan Soon , Thanabalu Thirumaran
Published: December 2016

Neural-Wiskott Aldrich Syndrome Protein (N-WASP) is expressed ubiquitously, regulates actin polymerization and is essential during mouse development. We have previously shown that N-WASP is critical for cell-ECM adhesion in fibroblasts. To characterize the role of N-WASP in fibroblast for skin development, we generated a conditional knockout mouse model in which fibroblast N-WASP was ablated using the Cre recombinase driven by Fibroblast Specific Protein promoter (Fsp-Cre). N-WASPFKO (N-WASPfl/fl; Fsp-cre) were born following Mendelian genetics, survived without any visible abnormalities for more than 1 year and were sexually reproductive, suggesting that expression of N-WASP in fibroblast is not critical for survival under laboratory conditions. Histological sections of N-WASPFKO mice skin (13 weeks old) showed thicker epidermis with higher percentage of cells staining for proliferation marker (PCNA), suggesting that N-WASP deficient fibroblasts promote keratinocyte proliferation. N-WASPFKO mice skin had elevated collagen content, elevated expression of FGF7 (keratinocyte growth factor) and TGFβ signaling proteins. Wound healing was faster in N-WASPFKO mice compared to control mice and N-WASP deficient fibroblasts were found to have enhanced collagen gel contraction properties. These results suggest that N-WASP deficiency in fibroblasts improves wound healing by growth factor-mediated enhancement of keratinocyte proliferation and increased wound contraction in mice.
UV Degradation and Recovery of Perovskite Solar Cells
Authors: Lee Sang-Won , Kim Seongtak , Bae Soohyun , Cho Kyungjin , Chung Taewon , Mundt Laura E. , Lee Seunghun , Park Sungeun , Park Hyomin , Schubert Martin C. , Glunz Stefan W. , Ko Yohan , Jun Yongseok , Kang Yoonmook , Lee Hae-Seok , Kim Donghwan
Published: December 2016

Although the power conversion efficiency of perovskite solar cells has increased from 3.81% to 22.1% in just 7 years, they still suffer from stability issues, as they degrade upon exposure to moisture, UV light, heat, and bias voltage. We herein examined the degradation of perovskite solar cells in the presence of UV light alone. The cells were exposed to 365 nm UV light for over 1,000 h under inert gas at <0.5 ppm humidity without encapsulation. 1-sun illumination after UV degradation resulted in recovery of the fill factor and power conversion efficiency. Furthermore, during exposure to consecutive UV light, the diminished short circuit current density (Jsc) and EQE continuously restored. 1-sun light soaking induced recovery is considered to be caused by resolving of stacked charges and defect state neutralization. The Jsc and EQE bounce-back phenomenon is attributed to the beneficial effects of PbI2 which is generated by the decomposition of perovskite material.
Energy metabolism regulated by HDAC inhibitor attenuates cardiac injury in hemorrhagic rat model
Authors: Kuai Qiyuan , Wang Chunyan , Wang Yanbing , Li Weijing , Zhang Gongqing , Qiao Zhixin , He Min , Wang Xuanlin , Wang Yu , Jiang Xingwei , Su Lihua , He Yuezhong , Ren Suping , Yu Qun
Published: December 2016

A disturbance of energy metabolism reduces cardiac function in acute severe hemorrhagic patients. Alternatively, adequate energy supply reduces heart failure and increases survival. However, the approach to regulating energy metabolism conductive to vital organs is limited, and the underlying molecular mechanism remains unknown. This study assesses the ability of histone deacetylase inhibitors (HDACIs) to preserve cardiac energy metabolism during lethal hemorrhagic injury. In the lethally hemorrhagic rat and hypoxic myocardial cells, energy metabolism and heart function were well maintained following HDACI treatment, as evident by continuous ATP production with normal cardiac contraction. Valproic acid (VPA) regulated the energy metabolism of hemorrhagic heart by reducing lactate synthesis and protecting the mitochondrial ultrastructure and respiration, which were attributable to the inhibition of lactate dehydrogenase A activity and the increased myeloid cell leukemia-1 (mcl-1) gene expression, ultimately facilitating ATP production and consumption. MCL-1, the key target of VPA, mediated this cardioprotective effect under acute severe hemorrhage conditions. Our results suggest that HDACIs promote cardioprotection by improving energy metabolism during hemorrhagic injury and could therefore be an effective strategy to counteract this process in the clinical setting.
The mechanism of transactivation regulation due to polymorphic short tandem repeats (STRs) using IGF1 promoter as a model
Authors: Chen Holly Y. , Ma Suk Ling , Huang Wei , Ji Lindan , Leung Vincent H. K. , Jiang Honglin , Yao Xiaoqiang , Tang Nelson L. S.
Published: December 2016

Functional short tandem repeats (STR) are polymorphic in the population, and the number of repeats regulates the expression of nearby genes (known as expression STR, eSTR). STR in IGF1 promoter has been extensively studied for its association with IGF1 concentration in blood and various clinical traits and represents an important eSTR. We previously used an in-vitro luciferase reporter model to examine the interaction between STRs and SNPs in IGF1 promoter. Here, we further explored the mechanism how the number of repeats of the STR regulates gene transcription. An inverse correlation between the number of repeats and the extent of transactivation was found in a haplotype consisting of three promoter SNPs (C-STR-T-T). We showed that these adjacent SNPs located outside the STR were required for the STR to function as eSTR. The C allele of rs35767 provides a binding site for CCAAT/enhancer-binding-protein δ (C/EBPD), which is essential for the gradational transactivation property of eSTR and FOXA3 may also be involved. Therefore, we propose a mechanism in which the gradational transactivation by the eSTR is caused by the interaction of one or more transcriptional complexes located outside the STR, rather than by direct binding to a repeat motif of the STR.
MicroRNAs modulate adaption to multiple abiotic stresses in Chlamydomonas reinhardtii
Authors: Gao Xiang , Zhang Fengge , Hu Jinlu , Cai Wenkai , Shan Ge , Dai Dongsheng , Huang Kaiyao , Wang Gaohong
Published: December 2016

MicroRNAs play an important role in abiotic stress responses in higher plants and animals, but their role in stress adaptation in algae remains unknown. In this study, the expression of identified and putative miRNAs in Chlamydomonas reinhardtii was assessed using quantitative polymerase chain reaction; some of the miRNAs (Cre-miR906-3p) were up-regulated, whereas others (Cre-miR910) were down-regulated when the species was subjected to multiple abiotic stresses. With degradome sequencing data, we also identified ATP4 (the d-subunit of ATP synthase) and NCR2 (NADPH: cytochrome P450 reductase) as one of the several targets of Cre-miR906-3p and Cre-miR910, respectively. Q-PCR data indicated that ATP4, which was expressed inversely in relation to Cre-miR906-3p under stress conditions. Overexpressing of Cre-miR906-3p enhanced resistance to multiple stresses; conversely, overexpressing of ATP4 produced the opposite effect. These data of Q-PCR, degradome sequencing and adaptation of overexpressing lines indicated that Cre-miR906-3p and its target ATP4 were a part of the same pathway for stress adaptation. We found that Cre-miR910 and its target NCR2 were also a part of this pathway. Overexpressing of Cre-miR910 decreased, whereas that of NCR2 increased the adaption to multiple stresses. Our findings suggest that the two classes of miRNAs synergistically mediate stress adaptation in algae.
Genome-wide characterisation and expression profile of the grapevine ATL ubiquitin ligase family reveal biotic and abiotic stress-responsive and development-related members
Authors: Ariani Pietro , Regaiolo Alice , Lovato Arianna , Giorgetti Alejandro , Porceddu Andrea , Camiolo Salvatore , Wong Darren , Castellarin Simone , Vandelle Elodie , Polverari Annalisa
Published: December 2016

The Arabidopsis Tóxicos en Levadura (ATL) protein family is a class of E3 ubiquitin ligases with a characteristic RING-H2 Zn-finger structure that mediates diverse physiological processes and stress responses in plants. We carried out a genome-wide survey of grapevine (Vitis vinifera L.) ATL genes and retrieved 96 sequences containing the canonical ATL RING-H2 domain. We analysed their genomic organisation, gene structure and evolution, protein domains and phylogenetic relationships. Clustering revealed several clades, as already reported in Arabidopsis thaliana and rice (Oryza sativa), with an expanded subgroup of grapevine-specific genes. Most of the grapevine ATL genes lacked introns and were scattered among the 19 chromosomes, with a high level of duplication retention. Expression profiling revealed that some ATL genes are expressed specifically during early or late development and may participate in the juvenile to mature plant transition, whereas others may play a role in pathogen and/or abiotic stress responses, making them key candidates for further functional analysis. Our data offer the first genome-wide overview and annotation of the grapevine ATL family, and provide a basis for investigating the roles of specific family members in grapevine physiology and stress responses, as well as potential biotechnological applications.
Melanosome transfer to keratinocyte in the chicken embryonic skin is mediated by vesicle release associated with Rho-regulated membrane blebbing
Authors: Tadokoro Ryosuke , Murai Hidetaka , Sakai Ken-ichiro , Okui Takahiro , Yokota Yasuhiro , Takahashi Yoshiko
Published: December 2016

During skin pigmentation in amniotes, melanin synthesized in the melanocyte is transferred to keratinocytes by a particle called the melanosome. Previous studies, mostly using dissociated cultured cells, have proposed several different models that explain how the melanosome transfer is achieved. Here, using a technique that labels the plasma membrane of melanocytes within a three-dimensional system that mimics natural tissues, we have visualized the plasma membrane of melanocytes with EGFP in chicken embryonic skin. Confocal time-lapse microscopy reveals that the melanosome transfer is mediated, at least in part, by vesicles produced by plasma membrane. Unexpectedly, the vesicle release is accompanied by the membrane blebbing of melanocytes. Blebs that have encapsulated a melanosome are pinched off to become vesicles, and these melanosome-containing vesicles are finally engulfed by neighboring keratinocytes. For both the membrane blebbing and vesicle release, Rho small GTPase is essential. We further show that the membrane vesicle-mediated melanosome transfer plays a significant role in the skin pigmentation. Given that the skin pigmentation in inter-feather spaces in chickens is similar to that in inter-hair spaces of humans, our findings should have important consequences in cosmetic medicine.
Calcium ions function as a booster of chromosome condensation
Authors: Phengchat Rinyaporn , Takata Hideaki , Morii Kenichi , Inada Noriko , Murakoshi Hideji , Uchiyama Susumu , Fukui Kiichi
Published: December 2016

Chromosome condensation is essential for the faithful transmission of genetic information to daughter cells during cell division. The depletion of chromosome scaffold proteins does not prevent chromosome condensation despite structural defects. This suggests that other factors contribute to condensation. Here we investigated the contribution of divalent cations, particularly Ca2+, to chromosome condensation in vitro and in vivo. Ca2+ depletion caused defects in proper mitotic progression, particularly in chromosome condensation after the breakdown of the nuclear envelope. Fluorescence lifetime imaging microscopy-Förster resonance energy transfer and electron microscopy demonstrated that chromosome condensation is influenced by Ca2+. Chromosomes had compact globular structures when exposed to Ca2+ and expanded fibrous structures without Ca2+. Therefore, we have clearly demonstrated a role for Ca2+ in the compaction of chromatin fibres.
Arabidopsis thaliana as a suitable model host for research on interactions between plant and foliar nematodes, parasites of plant shoot
Authors: Wang Dong-Wei , Peng Xiao-Fang , Xie Hui , Xu Chun-Ling , Cheng De-Qiang , Li Jun-Yi , Wu Wen-Jia , Wang Ke
Published: December 2016

The rice white tip nematode (RWTN), Aphelenchoides besseyi and the chrysanthemum foliar nematode (CFN), Aphelenchoides ritzemabosi are migratory plant parasitic nematodes that infect the aboveground parts of plants. In this research, Arabidopsis thaliana was infected by RWTN and CFN under indoor aseptic cultivation, and the nematodes caused recognizable symptoms in the leaves. Furthermore, RWTN and CFN completed their life cycles and proliferated. Therefore, A. thaliana was identified as a new host of RWTN and CFN. The optimum inoculum concentration for RWTN and CFN was 100 nematodes/plantlet, and the optimum inoculum times were 21 and 24 days, respectively. For different RWTN populations, the pathogenicity and reproduction rates were different in the A. thaliana Col-0 ecotype and were positively correlated. The optimum A. thaliana ecotypes were Col-0 and WS, which were the most susceptible to RWTN and CFN, respectively. Additionally, RWTN was ectoparasitic and CFN was ecto- and endoparasitic in A. thaliana. The RWTN and CFN migrated from inoculated leaves to the entire plantlet, and the number of nematodes in different parts of A. thaliana was not correlated with distance from the inoculum point. This is a detailed study of the behavior and infection process of foliar nematodes on A. thaliana.
The Disinfection Characteristics of Ebola Virus Outbreak Variants
Authors: Cook Bradley W. M. , Cutts Todd A. , Nikiforuk Aidan M. , Leung Anders , Kobasa Darwyn , Theriault Steven S.
Published: December 2016

The recent Ebola virus outbreak in West Africa has forced experts to re-evaluate their understanding of how to best disinfect areas contaminated with infectious bodily fluids. Recent research has found that Ebola virus remains viable in blood for 7–10 days making appropriate disinfection crucial to infection control. We sought to determine if the three most important outbreak variants ofZaire ebolavirus(Mayinga, Kikwit and Makona) exhibit separate phenotypes when challenged with a range of sodium hypochlorite (NaOCl) concentrations or 70% ethanol (EtOH) at average West African temperature. The time dependent killing of Ebola virus was evaluated by measuring infectious virus and viral RNA (vRNA), to determine if RNA detection is a viable method for decontamination measurement in areas without high containment laboratory access. Makona was less susceptible to weaker concentrations of NaOCl (0.05 and 0.1%) than Mayinga and Kikwit. At the recommended concentration of NaOCl (≥0.5%) all of the variants were inert after 5 minutes of contact time. Similarly, all variants were inactivated by 70% EtOH after 2.5 minutes, only Makona was detected at 1 minute. In multiple instances, high amounts of vRNA was detected in the absence of infectious virus, suggesting that it does not serve as an accurate measure of remaining infectivity after cleansing.
Improved in-cell structure determination of proteins at near-physiological concentration
Authors: Ikeya Teppei , Hanashima Tomomi , Hosoya Saori , Shimazaki Manato , Ikeda Shiro , Mishima Masaki , Güntert Peter , Ito Yutaka
Published: December 2016

Investigating three-dimensional (3D) structures of proteins in living cells by in-cell nuclear magnetic resonance (NMR) spectroscopy opens an avenue towards understanding the structural basis of their functions and physical properties under physiological conditions inside cells. In-cell NMR provides data at atomic resolution non-invasively, and has been used to detect protein-protein interactions, thermodynamics of protein stability, the behavior of intrinsically disordered proteins, etc. in cells. However, so far only a single de novo 3D protein structure could be determined based on data derived only from in-cell NMR. Here we introduce methods that enable in-cell NMR protein structure determination for a larger number of proteins at concentrations that approach physiological ones. The new methods comprise (1) advances in the processing of non-uniformly sampled NMR data, which reduces the measurement time for the intrinsically short-lived in-cell NMR samples, (2) automatic chemical shift assignment for obtaining an optimal resonance assignment, and (3) structure refinement with Bayesian inference, which makes it possible to calculate accurate 3D protein structures from sparse data sets of conformational restraints. As an example application we determined the structure of the B1 domain of protein G at about 250 μM concentration in living E. coli cells.
Genome analysis of Campylobacter concisus strains from patients with inflammatory bowel disease and gastroenteritis provides new insights into pathogenicity
Authors: Chung Heung Kit Leslie , Tay Alfred , Octavia Sophie , Chen Jieqiong , Liu Fang , Ma Rena , Lan Ruiting , Riordan Stephen M , Grimm Michael C. , Zhang Li
Published: December 2016

Campylobacter concisus is an oral bacterium that is associated with inflammatory bowel disease. C. concisus has two major genomospecies, which appear to have different enteric pathogenic potential. Currently, no studies have compared the genomes of C. concisus strains from different genomospecies. In this study, a comparative genome analysis of 36 C. concisus strains was conducted including 27 C. concisus strains sequenced in this study and nine publically available C. concisus genomes. The C. concisus core-genome was defined and genomospecies-specific genes were identified. The C. concisus core-genome, housekeeping genes and 23S rRNA gene consistently divided the 36 strains into two genomospecies. Two novel genomic islands, CON_PiiA and CON_PiiB, were identified. CON_PiiA and CON_PiiB islands contained proteins homologous to the type IV secretion system, LepB-like and CagA-like effector proteins. CON_PiiA islands were found in 37.5% of enteric C. concisus strains (3/8) isolated from patients with enteric diseases and none of the oral strains (0/27), which was statistically significant. This study reports the findings of C. concisus genomospecies-specific genes, novel genomic islands that contain type IV secretion system and putative effector proteins, and other new genomic features. These data provide novel insights into understanding of the pathogenicity of this emerging opportunistic pathogen.
Disentangling the roles of cholesterol and CD59 in intermedilysin pore formation
Authors: Boyd Courtney M. , Parsons Edward S. , Smith Richard A. G. , Seddon John M. , Ces Oscar , Bubeck Doryen
Published: December 2016

The plasma membrane provides an essential barrier, shielding a cell from the pressures of its external environment. Pore-forming proteins, deployed by both hosts and pathogens alike, breach this barrier to lyse target cells. Intermedilysin is a cholesterol-dependent cytolysin that requires the human immune receptor CD59, in addition to cholesterol, to form giant β-barrel pores in host membranes. Here we integrate biochemical assays with electron microscopy and atomic force microscopy to distinguish the roles of these two receptors in mediating structural transitions of pore formation. CD59 is required for the specific coordination of intermedilysin (ILY) monomers and for triggering collapse of an oligomeric prepore. Movement of Domain 2 with respect to Domain 3 of ILY is essential for forming a late prepore intermediate that releases CD59, while the role of cholesterol may be limited to insertion of the transmembrane segments. Together these data define a structural timeline for ILY pore formation and suggest a mechanism that is relevant to understanding other pore-forming toxins that also require CD59.