bluuebunny/crossref_metadata_2025 huggingface dataset:
The Cycala Flying Machine
Authors: Zimmerman Charles
Published: February 2017

In my last communication to the Society it Was stated that I had means by which I could vibrate my thirty-five-foot expanse of wing machine, that if it did not go, “ I would try again.” Well, it didn't go. Now, some one may say, “ that was to be expected; ” however, we can say, in rebuttal, that if hope did not burn brightly in the average inventor's breast, or his energy would fag in the effort to produce in material form his conception, or the unsympathetic attitude of his too conservative, yet esteemed contemporaries would cause him to desist, we would have no improvements, and progress would cease, except, perhaps, in the old beaten paths. It is far easier and much more pleasant to record and report success than failure. It is said that success is often the result of failure, but in the pursuit of the ignis fatuus of aëronautics, failure has been broadly written across all effort to wrest from the air that necessary grip and traction which will give us suspension and propulsion as does a marine vessel in water or an automobile on land.
Cloud Photography From Balloons
Authors: Bacon J. M.
Published: February 2017

The aeronaut can scarcely turn his camera to better account than in the pursuit of cloud photography. Snap–shots of objects on the earth taken from short range overhead are generally more curious than interesting, and extended views from greater heights, however impressive to the observer, seldom make satisfactory photographs, not only through lack of detail, but owing also to the haze that too often veils the landscape at the height— say of 1,000 ft. and upwards. Speaking generally, through the greater part of any balloon voyage worthy of the name, successful views of the country are out of the question. On the other hand, on days that are not altogether cloudless, there is often opportunity at nearly all heights for interesting and valuable work in photographing all features of the cloudscape, from the mere withering cloudlet that wanders by to the piles and masses of dense cloud that make up the scenery of a full sky.
Wings versus Aëroplanes
Authors: Moore R. F.
Published: February 2017

There are two mechanical arrangements, heavier than air, which have been proposed for obtaining flight, namely, wings and aeroplanes. The latter is the one chiefly in favour with the public as there have been more or less successful experiments brought to its notice. There are, however, many advantages for a machine made with wings in imitation of a bird or flying fox as in Nature.

Wings with their large spread and slow motion give more effective action on the air than the small blades of a screw propeller. It is known from experiment that a large surface working slowly is more efficient than a small one working rapidly in a rarefied medium such as air, for the same power expended.
Shop Organisation: A Simple Scheme
Authors: John W. E.
Published: February 2017

During my visit to Great Britain I have been surprised to find how many factories have sprung up during the war, which whilst producing munitions of a highly complicated character lack a staff, the members of which as a whole possess that long and careful experience in technical production always considered necessary in the qualifications of men for executive or responsible positions.

Yet the fact remains that these concerns are producing, and the product in many cases is of a high quality. We are, however, living in exceptional times, when competition—in the true sense of the word—is absent; but if the best is to be obtained now and in the future, when these factories will have to strain every effort for their existence, it will be necessary that production on a strictly economical basis be considered.

My experience shows that in a number of cases there exists a misconception of what a proper system of control means, and the advantage accruing there from is unknown.
Skin Friction
Authors: Ellis Williams W.
Published: February 2017

Among the various experimental data which are required in the discussion of the theory and design of the aeroplane, there are none of greater importance than those relating to surface friction, while at the same time there are none about which greater uncertainty prevails.

Owing to the difficulty of separating skin friction from head resistance, very little can be learnt from observations on actual machines in flight, while on the other hand, if we turn to laboratory experiments on the resistance of planes, we are met with the most bewildering variations in the values obtained for it. Many of the most careful experimenters make out that it is quite inappreciable while others maintain that it is from 1—4 per cent. of the normal pressure, and therefore forms an important part of the drift at small angles of attack.
Fighting in the Air
Authors: Patrick Cochrane
Published: February 2017

The entire science of aerial fighting has developed, as everyone knows, since the beginning of this war, in other words in the short space of four years.

To–night I am going to attempt to give you an outline of the various stages through which aerial fighting has progressed to its present state of efficiency, though it would be foolish to claim that we have even begun to realise the methods and tactics which will be employed in the future.

All through the history of aerial fighting we find two main governing factors, and I would ask you to notice how these affect each step. These two factors are:—

(1)

Field of fire.

(2)

Field of view.

In talking of the latter, I shall be constantly mentioning blind spots. By a blind spot is meant anywhere in the sky which is hidden by the planes, tail or fuselage, from the pilot as he sits in his cockpit.
The Coming Airship
Authors: Waterlow C. M.
Published: February 2017

The subject of my paper is the airship of to-morrow, and if I look at it rather from the point of view of military requirements, you must bear in mind that it is these requirements which have made it what it is. Commercial needs and even Naval needs have played a very small part hitherto in its development, though they may be expected to exert considerable influence on its progress in future.

Looking back over the past few years, we find an extraordinary prejudice against airships in this country, fostered in the most amazing manner by the Press, both lay and technical. This did not begin to dissipate until the autumn of 1912, just over a year ago.

As late as October, 1912, the “Times” wrote a leading article on the folly of spending money on airships, taking as its text the accident to “Gamma” after the manœuvres of that year.
The Science of Fast Flying
Authors: Weymann C. T.
Published: February 2017

In this lecture, which the Council of the Aeronautical Society, through Mr. Griffith Brewer, have done me the great honour to ask me to deliver before you, I propose to consider the rôle of speed or fast flying in aeroplanes.

As soon as aeroplanes were able to fly, the next preoccupation of designers was to make them fly as fast as possible. In order to stimulate constructors, Mr. James Gordon-Bennett created his International Aviation Cup, destined to consecrate every year the fastest flying machine. This contest, held yearly since 1909, will give us a valuable basis to examine the lessons which aviation has been able to draw from pure speed.
The Theory of the Gravity-Controlled Air Speed Indicator as Applied to Dynamic Lift Flying Machines
Authors: Booth Harris
Published: February 2017

As far as the writer is aware, Mr. Horace Darwin was the first to call attention to the fact that there is an essential difference in action between a spring-controlled and a gravity-controlled air speed indicator on an aeroplane.

This fact was put forward in the Wilbur Wright lecture of last year and the conclusion then reached was definitely in favour of the use of the gravity type, as being more useful to a pilot on a steeply banked turn.

Since that date, however, the discovery has been made that this type fails to give warning of “ stalling ” in straight flight (the very purpose for which the instrument is installed) and equally fails under the conditions of a banked turn.

The writer believes that he has the priority in this discovery, and therefore takes the present opportunity of publishing the following formal proof of the scientific theorem involved.
Supplementary Notes on Drzewiecki's Theory of Airscrews
Authors: Low Archibald R.
Published: February 2017

In the previous contribution and in the reply to the discussion justice was not done to several points.

It was made clear that a circulation of air was established round the airscrew at standstill, creating a certain velocity before the airscrew disc in such a way as to modify fundamentally the thrust on the blades. But it was not explicitly stated that at full speed (of the aeroplane) this component of velocity was ignored altogether and each blade was assumed to be attacking “ still ” air.

This does not mean that the air was still until the blade actually drew level with it, for, if the analogy with lifting surfaces holds, we know that at a distance of twice the chord width in front of the blade the air is appreciably disturbed, and this disturbance may be by no means negligible even at four or five times the chord's width in front of the instantaneous position of the blade.
The Use of Jigs in Aeroplane Manufacture
Authors: Borlase Matthews R.
Published: February 2017

A new industry calls for new methods—autrea jours, autres mceurs—and the aeroplane industry is therefore not exceptional in demanding many departures from recognised woodworking practice. In the first place the number of machines required to–day is so large that their construction should be described as a manufacturing rather than a building operation. That is to say, they should preferably be almost entirely put together by the aid of accurate machinery instead of being dependent to such an extent upon the skill of the individual workman, in trying and fitting one part to another until the whole is built up. In this connection it may be remarked that the design of the metal fittings for aeroplanes is not such as to call for any radical departure from previous high class small metal working practice. It is the woodworking side of the business which presents the new scope for initiative. It is this latter aspect, therefore, which will be considered here.
The Wind Channel: Its Design and Use
Authors: Pannell J. R.
Published: February 2017

It has long been realised that experiments in the laboratory on small models afford in certain cases a means of obtaining, cheaply and rapidly, information on the behaviour of the actual structure under the conditions in which it is to be used. This plan has been adopted in many branches of science, and in none to a larger extent than in naval and aeronautical architecture. The problems to be investigated are usually those connected with the motion of bodies through a fluid, but if we accept the principle of relative motion we have an alternative method open to us for our model experiments. We may, if we wish, reverse the conditions and set the fluid in motion, the model remaining stationary. Generally speaking, one plan has been adopted in naval architecture and the other in aeronautics. In the former case models are towed through water in a ship tank, while in the latter they are placed in a tube through which air is passed.
Flapping Flight
Authors: Fitzgerald Maurice F.
Published: February 2017

A paper on “Flapping Flight of Aeroplanes ” by the present writer was communicated by the late Professor G. F. FitzGerald to the “ Proceedings ” of the Royal Society (Vol. 64, pp. 420-430) in 1899. At that date much that is now almost common knowledge concerning the mechanics of flight was little thought of, much less understood, practical aviation did not exist, and a limited supply of experimental results presented confusing specimens of discordant and unreliable data to the inquirer. The development, during the last eight years, of the practice and science of aviation, seems to justify a review of the paper1 of 1899 in the light of better information, and of a better understanding of the influence of head resistance and other things, ignored fifteen years ago.
Einfluss von achtsamkeitsbasierten Interventionen auf Exekutive Funktionen im Kindesalter
Authors: Jansen Petra , Schulz Anja , Nottberg Carla
Published: February 2017

Zusammenfassung. Exekutive Funktionen (EF) haben eine große Bedeutung in der kindlichen Entwicklung. Ziel der vorliegenden Übersichtsarbeit war es, bisherige Untersuchungen zum Einfluss von achtsamkeitsbasierten Methoden auf die Exekutiven Funktionen von Kindern systematisch zusammenzufassen. In einer entsprechenden Literaturrecherche wurden insgesamt 331 Studien zum Thema identifiziert. Nach Anwendung der Einschlusskriterien (Exekutive Funktionen als abhängige Variable, achtsamkeitsbasiertes Training als unabhängige Variable, Vorhandensein einer Kontrollgruppe, Alter der Kinder ≤ 13 Jahre) verblieben 10 Arbeiten. Die untersuchten Achtsamkeitstrainings waren sehr heterogen und häufig von den Forschern selbst entwickelt. Die meisten Studien verglichen Achtsamkeitstrainings mit nicht aktiven Kontrollgruppen (9/10) und führten kein Follow-up durch (9/10). Die Ergebnisse weisen darauf hin, dass sich Kinder durch ein Achtsamkeitstraining im Vergleich zu einer Kontrollgruppe in ihrer Aufmerksamkeitsleistung, Inhibitionsleistung, kognitiven Flexibilität und ihrem Arbeitsgedächtnis verbesserten. Es konnte vereinzelt ein Zusammenhang zwischen niedrigen Ausgangswerten in den EF und stärkeren Effekten der Trainingsprogramme nachgewiesen werden.
Multiple approaches to immunotherapy ‐ the new pillar of cancer treatment
Authors: Smyth Mark J
Published: February 2017

The April 2017 issue of Immunology & Cell Biology contains a Special Feature on Cancer Immunotherapy. This series of reviews highlights some of the recent advances in mobilizing effective host immunity to cancer. Cancer immunotherapy is at a critical and exciting stage of development. Progress in our understanding of cancer immunotherapy has been dramatic over recent years and we have selected six articles to highlight in this Special Feature. The Special Feature begins with an overview of the approaches to targeting inflammation in the cancer microenvironment and follows with a focus of extracellular adenosine as a major immunosuppressive metabolite in tumours. Two subsequent articles detail advances in antibody engineering for engaging the ideal effector responses in tumours and the Special Feature finishes with two articles that explore new approaches in adoptive cellular therapy targeted at tumor and virus specific antigens in tumors. Immunology & C ell Biology thanks the coordinator of this Special Feature ‐ Mark Smyth ‐ for his planning and input.
RIP1 autophosphorylation is promoted by mitochondrial ROS and is essential for RIP3 recruitment into necrosome
Authors: Zhang Yingying , Su Sheng Sean , Zhao Shubo , Yang Zhentao , Zhong Chuan-Qi , Chen Xin , Cai Qixu , Yang Zhang-Hua , Huang Deli , Wu Rui , Han Jiahuai
Published: February 2017

Necroptosis is a type of programmed cell death with great significance in many pathological processes. Tumour necrosis factor-α(TNF), a proinflammatory cytokine, is a prototypic trigger of necroptosis. It is known that mitochondrial reactive oxygen species (ROS) promote necroptosis, and that kinase activity of receptor interacting protein 1 (RIP1) is required for TNF-induced necroptosis. However, how ROS function and what RIP1 phosphorylates to promote necroptosis are largely unknown. Here we show that three crucial cysteines in RIP1 are required for sensing ROS, and ROS subsequently activates RIP1 autophosphorylation on serine residue 161 (S161). The major function of RIP1 kinase activity in TNF-induced necroptosis is to autophosphorylate S161. This specific phosphorylation then enables RIP1 to recruit RIP3 and form a functional necrosome, a central controller of necroptosis. Since ROS induction is known to require necrosomal RIP3, ROS therefore function in a positive feedback circuit that ensures effective induction of necroptosis.
Humans have already increased the risk of major disruptions to Pacific rainfall
Authors: Power Scott B. , Delage François P. D. , Chung Christine T. Y. , Ye Hua , Murphy Bradley F.
Published: February 2017

Intermittent disruptions to rainfall patterns and intensity over the Pacific Ocean lasting up to ∼ 1 year have major impacts on severe weather, agricultural production, ecosystems, and disease within the Pacific, and in many countries beyond. The frequency with which major disruptions to Pacific rainfall occur has been projected to increase over the 21st century, in response to global warming caused by large 21st century greenhouse gas emissions. Here we use the latest generation of climate models to show that humans may have contributed to the major disruption that occurred in the real world during the late 20th century. We demonstrate that although marked and sustained reductions in 21st century anthropogenic greenhouse gas emissions can greatly moderate the likelihood of major disruption, elevated risk of occurrence appears locked in now, and for at least the remainder of the 21st century.
p190-B RhoGAP and intracellular cytokine signals balance hematopoietic stem and progenitor cell self-renewal and differentiation
Authors: Hinge Ashwini , Xu Juying , Javier Jose , Mose Eucabeth , Kumar Sachin , Kapur Reuben , Srour Edward F. , Malik Punam , Aronow Bruce J. , Filippi Marie-Dominique
Published: February 2017

The mechanisms regulating hematopoietic stem and progenitor cell (HSPC) fate choices remain ill-defined. Here, we show that a signalling network of p190-B RhoGAP-ROS-TGF-β-p38MAPK balances HSPC self-renewal and differentiation. Upon transplantation, HSPCs express high amounts of bioactive TGF-β1 protein, which is associated with high levels of p38MAPK activity and loss of HSC self-renewal in vivo. Elevated levels of bioactive TGF-β1 are associated with asymmetric fate choice in vitro in single HSPCs via p38MAPK activity and this is correlated with the asymmetric distribution of activated p38MAPK. In contrast, loss of p190-B, a RhoGTPase inhibitor, normalizes TGF-β levels and p38MAPK activity in HSPCs and is correlated with increased HSC self-renewal in vivo. Loss of p190-B also promotes symmetric retention of multi-lineage capacity in single HSPC myeloid cell cultures, further suggesting a link between p190-B-RhoGAP and non-canonical TGF-β signalling in HSPC differentiation. Thus, intracellular cytokine signalling may serve as ‘fate determinants’ used by HSPCs to modulate their activity.
Electron–acoustic phonon coupling in single crystal CH3NH3PbI3 perovskites revealed by coherent acoustic phonons
Authors: Mante Pierre-Adrien , Stoumpos Constantinos C. , Kanatzidis Mercouri G. , Yartsev Arkady
Published: February 2017

Despite the great amount of attention CH3NH3PbI3 has received for its solar cell application, intrinsic properties of this material are still largely unknown. Mobility of charges is a quintessential property in this aspect; however, there is still no clear understanding of electron transport, as reported values span over three orders of magnitude. Here we develop a method to measure the electron and hole deformation potentials using coherent acoustic phonons generated by femtosecond laser pulses. We apply this method to characterize a CH3NH3PbI3 single crystal. We measure the acoustic phonon properties and characterize electron-acoustic phonon scattering. Then, using the deformation potential theory, we calculate the carrier intrinsic mobility and compare it to the reported experimental and theoretical values. Our results reveal high electron and hole mobilities of 2,800 and 9,400 cm2 V−1 s−1, respectively. Comparison with literature values of mobility demonstrates the potential role played by polarons in charge transport in CH3NH3PbI3.
LncRNA AK023948 is a positive regulator of AKT
Authors: Koirala Pratirodh , Huang Jianguo , Ho Tsui-Ting , Wu Fangting , Ding Xianfeng , Mo Yin-Yuan
Published: February 2017

Despite the overwhelming number of human long non-coding RNAs (lncRNAs) reported so far, little is known about their physiological functions for the majority of them. The present study uses a CRISPR/Cas9-based synergistic activation mediator (SAM) system to identify potential lncRNAs capable of regulating AKT activity. Among lncRNAs identified from this screen, we demonstrate that AK023948 is a positive regulator for AKT. Knockout of AK023948 suppresses, whereas rescue with AK023948 restores the AKT activity. Mechanistically, AK023948 functionally interacts with DHX9 and p85. Importantly, AK023948 is required for the interaction between DHX9 and p85 to hence the p85 stability and promote AKT activity. Finally, AK023948 is upregulated in breast cancer; interrogation of TCGA data set indicates that upregulation of DHX9 in breast cancer is associated with poor survival. Together, this study demonstrates two previously uncharacterized factors AK023948 and DHX9 as important players in the AKT pathway, and that their upregulation may contribute to breast tumour progression.
Volumetric Spatial Correlations of Neurovascular Coupling Studied using Single Pulse Opto-fMRI
Authors: Christie Isabel N. , Wells Jack A. , Kasparov Sergey , Gourine Alexander V. , Lythgoe Mark F.
Published: February 2017

Neurovascular coupling describes the link between neuronal activity and cerebral blood flow. This relationship has been the subject of intense scrutiny, with most previous work seeking to understand temporal correlations that describe neurovascular coupling. However, to date, the study of spatial correlations has been limited to two-dimensional mapping of neuronal or vascular derived signals emanating from the brain’s surface, using optical imaging techniques. Here, we investigate spatial correlations of neurovascular coupling in three dimensions, by applying a single 10 ms pulse of light to trigger optogenetic activation of cortical neurons transduced to express channelrhodopsin2, with concurrent fMRI. We estimated the spatial extent of increased neuronal activity using a model that takes into the account the scattering and absorption of blue light in brain tissue together with the relative density of channelrhodopsin2 expression across cortical layers. This method allows precise modulation of the volume of activated tissue in the cerebral cortex with concurrent three-dimensional mapping of functional hyperemia. Single pulse opto-fMRI minimizes adaptation, avoids heating artefacts and enables confined recruitment of the neuronal activity. Using this novel method, we present evidence for direct proportionality of volumetric spatial neurovascular coupling in the cerebral cortex.
Comparative Study of the Collective Dynamics of Proteins and Inorganic Nanoparticles
Authors: Haddadian Esmael J. , Zhang Hao , Freed Karl F. , Douglas Jack F.
Published: February 2017

Molecular dynamics simulations of ubiquitin in water/glycerol solutions are used to test the suggestion by Karplus and coworkers that proteins in their biologically active state should exhibit a dynamics similar to ‘surface-melted’ inorganic nanoparticles (NPs). Motivated by recent studies indicating that surface-melted inorganic NPs are in a ‘glassy’ state that is an intermediate dynamical state between a solid and liquid, we probe the validity and significance of this proposed analogy. In particular, atomistic simulations of ubiquitin in solution based on CHARMM36 force field and pre-melted Ni NPs (Voter-Chen Embedded Atom Method potential) indicate a common dynamic heterogeneity, along with other features of glass-forming (GF) liquids such as collective atomic motion in the form of string-like atomic displacements, potential energy fluctuations and particle displacements with long range correlations (‘colored’ or ‘pink’ noise), and particle displacement events having a power law scaling in magnitude, as found in earthquakes. On the other hand, we find the dynamics of ubiquitin to be even more like a polycrystalline material in which the α-helix and β-sheet regions of the protein are similar to crystal grains so that the string-like collective atomic motion is concentrated in regions between the α-helix and β-sheet domains.
Transcriptional firing helps to drive NETosis
Authors: Khan Meraj A. , Palaniyar Nades
Published: February 2017

Neutrophils are short-lived innate immune cells. These cells respond quickly to stimuli, and die within minutes to hours; the relevance of DNA transcription in dying neutrophils remains an enigma for several decades. Here we show that the transcriptional activity reflects the degree of DNA decondensation occurring in both NADPH oxidase 2 (Nox)-dependent and Nox-independent neutrophil extracellular trap (NET) formation or NETosis. Transcriptomics analyses show that transcription starts at multiple loci in all chromosomes earlier in the rapid Nox-independent NETosis (induced by calcium ionophore A23187) than Nox-dependent NETosis (induced by PMA). NETosis-specific kinase cascades differentially activate transcription of different sets of genes. Inhibitors of transcription, but not translation, suppress both types of NETosis. In particular, promoter melting step is important to drive NETosis (induced by PMA, E. coli LPS, A23187, Streptomyces conglobatus ionomycin). Extensive citrullination of histones in multiple loci occurs only during calcium-mediated NETosis, suggesting that citrullination of histone contributes to the rapid DNA decondensation seen in Nox-independent NETosis. Furthermore, blocking transcription suppresses both types of NETosis, without affecting the reactive oxygen species production that is necessary for antimicrobial functions. Therefore, we assign a new function for transcription in neutrophils: Transcriptional firing, regulated by NETosis-specific kinases, helps to drive NETosis.
Quantification of Detergents Complexed with Membrane Proteins
Authors: Chaptal Vincent , Delolme Frédéric , Kilburg Arnaud , Magnard Sandrine , Montigny Cédric , Picard Martin , Prier Charlène , Monticelli Luca , Bornert Olivier , Agez Morgane , Ravaud Stéphanie , Orelle Cédric , Wagner Renaud , Jawhari Anass , Broutin Isabelle , Pebay-Peyroula Eva , Jault Jean-Michel , Kaback H. Ronald , le Maire Marc , Falson Pierre
Published: February 2017

Most membrane proteins studies require the use of detergents, but because of the lack of a general, accurate and rapid method to quantify them, many uncertainties remain that hamper proper functional and structural data analyses. To solve this problem, we propose a method based on matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) that allows quantification of pure or mixed detergents in complex with membrane proteins. We validated the method with a wide variety of detergents and membrane proteins. We automated the process, thereby allowing routine quantification for a broad spectrum of usage. As a first illustration, we show how to obtain information of the amount of detergent in complex with a membrane protein, essential for liposome or nanodiscs reconstitutions. Thanks to the method, we also show how to reliably and easily estimate the detergent corona diameter and select the smallest size, critical for favoring protein-protein contacts and triggering/promoting membrane protein crystallization, and to visualize the detergent belt for Cryo-EM studies.
Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota
Authors: Harach T. , Marungruang N. , Duthilleul N. , Cheatham V. , Mc Coy K. D. , Frisoni G. , Neher J. J. , Fåk F. , Jucker M. , Lasser T. , Bolmont T.
Published: February 2017

Alzheimer’s disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer’s disease is not known. To this end we sequenced bacterial 16S rRNA from fecal samples of Aβ precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice. Subsequently we generated germ-free APP transgenic mice and found a drastic reduction of cerebral Aβ amyloid pathology when compared to control mice with intestinal microbiota. Importantly, colonization of germ-free APP transgenic mice with microbiota from conventionally-raised APP transgenic mice increased cerebral Aβ pathology, while colonization with microbiota from wild-type mice was less effective in increasing cerebral Aβ levels. Our results indicate a microbial involvement in the development of Abeta amyloid pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases.
Intestinal cancer stem cells marked by Bmi1 or Lgr5 expression contribute to tumor propagation via clonal expansion
Authors: Yanai Hirotsugu , Atsumi Naho , Tanaka Toshihiro , Nakamura Naohiro , Komai Yoshihiro , Omachi Taichi , Tanaka Kiyomichi , Ishigaki Kazuhiko , Saiga Kazuho , Ohsugi Haruyuki , Tokuyama Yoko , Imahashi Yuki , Ohe Shuichi , Hisha Hiroko , Yoshida Naoko , Kumano Keiki , Kon Masanori , Ueno Hiroo
Published: February 2017

Although the existence of cancer stem cells in intestine tumors has been suggested, direct evidence has not been yet provided. Here, we showed, using the multicolor lineage-tracing method and mouse models of intestinal adenocarcinoma and adenoma that Bmi1- or Lgr5- positive tumorigenic cells clonally expanded in proliferating tumors. At tumor initiation and during tumor propagation in the colon, the descendants of Lgr5-positive cells clonally proliferated to form clusters. Clonal analysis using ubiquitous multicolor lineage tracing revealed that colon tumors derived from Lgr5-positive cells were monoclonal in origin but eventually merged with neighboring tumors, producing polyclonal tumors at the later stage. In contrast, the origin of small intestine tumors was likely polyclonal, and during cancer progression some clones were eliminated, resulting in the formation of monoclonal tumors, which could merge similar to colon tumors. These results suggest that in proliferating intestinal neoplasms, Bmi1- or Lgr5-positive cells represent a population of cancer stem cells, whereas Lgr5-positive cells also function as cells-of-origin for intestinal tumors.
Association of Body Mass Index with the Tuberculosis Infection: a Population-based Study among 17796 Adults in Rural China
Authors: Zhang Haoran , Li Xiangwei , Xin Henan , Li Hengjing , Li Mufei , Lu Wei , Bai Liqiong , Wang Xinhua , Liu Jianmin , Jin Qi , Gao Lei
Published: February 2017

Body mass index (BMI) has been shown to be associated with host susceptibility to several infections. However, the link between BMI and the risk of tuberculosis (TB) infection has been sparsely studied in China and in worldwide. Based on the baseline survey of a population-based, prospective study in rural China, the association between BMI and TB infection among adults was estimated by means of cross-sectional analysis. TB infection status was tested using QuantiFERON-TB Gold In-Tube (QFT), a commercial of interferon-γ release assay (IGRA). Totally, 17796 eligible participants aged ≥18 years from 4 study sites, were included in the analysis. 21.76% (3873/17796) were observed to be QFT positive. Age and gender standardized prevalence ranged from 16.49% to 23.81% across the study sites. 42.19% study participants were obese/overweight with BMI ≥ 24.0 kg/m2. BMI ≥ 28.0 kg/m2 was observed to be independently associated with QFT positivity (adjusted odds ratio: 1.17, 95% confidence interval: 1.04–1.33). The strength of the association was found to be geographically diversity, which might be explained, at least partly, by the varied local TB epidemic status. Our results suggest that individuals with obesity might be one important target population for TB infection control in rural China.
Microscopic description for the emergence of collective dissipation in extended quantum systems
Authors: Galve Fernando , Mandarino Antonio , Paris Matteo G. A. , Benedetti Claudia , Zambrini Roberta
Published: February 2017

Practical implementations of quantum technology are limited by unavoidable effects of decoherence and dissipation. With achieved experimental control for individual atoms and photons, more complex platforms composed by several units can be assembled enabling distinctive forms of dissipation and decoherence, in independent heat baths or collectively into a common bath, with dramatic consequences for the preservation of quantum coherence. The cross-over between these two regimes has been widely attributed in the literature to the system units being farther apart than the bath’s correlation length. Starting from a microscopic model of a structured environment (a crystal) sensed by two bosonic probes, here we show the failure of such conceptual relation, and identify the exact physical mechanism underlying this cross-over, displaying a sharp contrast between dephasing and dissipative baths. Depending on the frequency of the system and, crucially, on its orientation with respect to the crystal axes, collective dissipation becomes possible for very large distances between probes, opening new avenues to deal with decoherence in phononic baths.
Ocular Reflex Phase during Off-Vertical Axis Rotation in Humans is Modified by Head-Turn-On-Trunk Position
Authors: Douglas Samantha B. , Clément Gilles , Denise Pierre , Wood Scott J.
Published: February 2017

Constant velocity Off-Vertical Axis Rotation (OVAR) imposes a continuously varying orientation of the head and body relative to gravity, which generates a modulation of horizontal (conjugate and vergence), vertical, and torsional eye movements. We introduced the head-turn-on-trunk paradigm during OVAR to examine the extent to whether the modulation of these ocular reflexes is mediated by graviceptors in the head, i.e., otoliths, versus other body graviceptors. Ten human subjects were rotated in darkness about their longitudinal axis 20° off-vertical at a constant velocity of 45 and 180°/s, corresponding to 0.125 and 0.5 Hz. Binocular responses were obtained with the head and trunk aligned, and then with the head turned relative to the trunk 40° to the right or left of center. The modulation of vertical and torsional eye position was greater at 0.125 Hz while the modulation of horizontal and vergence slow phase velocity was greater at 0.5 Hz. The amplitude modulation was not significantly altered by head-on-trunk position, but the phases shifted towards alignment with the head. These results are consistent with the modulation of ocular reflexes during OVAR being primarily mediated by the otoliths in response to the sinusoidally varying linear acceleration along the interaural and naso-occipital head axis.
Mycobacterium tuberculosis exploits the PPM1A signaling pathway to block host macrophage apoptosis
Authors: Schaaf Kaitlyn , Smith Samuel R. , Duverger Alexandra , Wagner Frederic , Wolschendorf Frank , Westfall Andrew O. , Kutsch Olaf , Sun Jim
Published: February 2017

The ability to suppress host macrophage apoptosis is essential for M. tuberculosis (Mtb) to replicate intracellularly while protecting it from antibiotic treatment. We recently described that Mtb infection upregulated expression of the host phosphatase PPM1A, which impairs the antibacterial response of macrophages. Here we establish PPM1A as a checkpoint target used by Mtb to suppress macrophage apoptosis. Overproduction of PPM1A suppressed apoptosis of Mtb-infected macrophages by a mechanism that involves inactivation of the c-Jun N-terminal kinase (JNK). Targeted depletion of PPM1A by shRNA or inhibition of PPM1A activity by sanguinarine restored JNK activation, resulting in increased apoptosis of Mtb-infected macrophages. We also demonstrate that activation of JNK by subtoxic concentrations of anisomycin induced selective apoptotic killing of Mtb-infected human macrophages, which was completely blocked in the presence of a specific JNK inhibitor. Finally, selective killing of Mtb-infected macrophages and subsequent bacterial release enabled rifampicin to effectively kill Mtb at concentrations that were insufficient to act against intracellular Mtb, providing proof of principle for the efficacy of a “release and kill” strategy. Taken together, these findings suggest that drug-induced selective apoptosis of Mtb-infected macrophages is achievable.
Quantifying tumor associated macrophages in breast cancer: a comparison of iron and fluorine-based MRI cell tracking
Authors: Makela Ashley V. , Gaudet Jeffrey M. , Foster Paula J.
Published: February 2017

Tumor associated macrophages (TAMs) are associated with tumor growth and metastasis. MRI can detect TAMs labeled with iron oxide (USPIO) or perfluorocarbon (PFC) agents. This study compared these two cell tracking approaches for imaging TAMs in vivo. 4T1 tumors were imaged with MRI at 4 days or 3 weeks post cell implantation after intravenous (i.v.) administration of either USPIO or PFC. Signal loss was detected within tumors at both time points post USPIO. Images acquired at 4 days demonstrated signal loss encompassing the entire tumor and around the periphery at 3 weeks. Number of black voxels suggested higher numbers of TAMs in the tumor at the later time point. After PFC administration, Fluorine-19 (19F) signal was detected in a similar spatial distribution as signal loss post USPIO. 19F signal quantification revealed that the number of 19F spins was not significantly different at the two time points, suggesting a similar number of TAMs were present in tumors but accumulated in different regions. 19F signal was higher centrally in tumors at 4 days and heterogenous around the periphery at 3 weeks. This study revealed that 19F-based cell tracking methods better represent TAM density and provides additional information not achievable with iron-based methods.
Effect of domestication on the genetic diversity and structure of Saccharina japonica populations in China
Authors: Zhang Jie , Wang Xiuliang , Yao Jianting , Li Qiuying , Liu Fuli , Yotsukura Norishige , Krupnova Tatiana N. , Duan Delin
Published: February 2017

Saccharina japonica is a commercially and ecologically important seaweed and is an excellent system for understanding the effects of domestication on marine crops. In this study, we used 19 selected simple sequence repeat (SSR) markers to investigate the influence of domestication on the genetic diversity and structure of S. japonica populations. Wild kelp populations exhibited higher genetic diversity than cultivated populations based on total NA, HE, HO, NP and AR. Discriminant analysis of principal components (DAPC), a neighbour-joining (NJ) tree and STRUCTURE analyses indicated that S. japonica populations could be divided into two groups (a cultivated/introduced group and a wild indigenous group) with significant genetic differentiation (P < 0.0001). Divergent selection, continuous inbreeding and inter-specific hybridization have caused the divergence of these two genetically separate gene pools. The significant genetic differentiation between northern and southern cultivated populations appears to be due to inter-specific hybridization and wild germplasm introduction during the domestication process. In addition, the cultivation of S. japonica has not resulted in any serious genetic disturbance of wild introduced S. japonica populations. An understanding of the genetic diversity and genetic structure of domesticated S. japonica will be necessary for further genetic improvement and effective use of germplasm.
Transmissible endoplasmic reticulum stress from myocardiocytes to macrophages is pivotal for the pathogenesis of CVB3-induced viral myocarditis
Authors: Zhang Hui , Yue Yan , Sun Tianle , Wu Xuejie , Xiong Sidong
Published: February 2017

Infiltrating macrophages have been proven as a pivotal pathological inflammatory cell subset in coxsackievirus B3 (CVB3) induced viral myocarditis. However, the mechanisms underlying the initiation and promotion of macrophage pro-inflammatory responses are still blur. We previously reported that cardiac ER stress contributed to CVB3-induced myocarditis by augmenting inflammation. In this study, we focused on the influence of ER stress on the macrophage inflammatory responses in the viral myocarditis. We found that ER stress was robustly induced in the cardiac infiltrating macrophages from CVB3-infected mice, and robustly facilitated the production of pro-inflammatory cytokines (IL-6, IL-12, MCP-1 and IP-10). Consistently, adoptive transfer of ER stressed macrophages significantly worsened the viral myocarditis; while transfer of ER stress-inhibited macrophages obviously alleviated the myocarditis. To our surprise, this significantly activated ER stress was not directly caused by the virus stimulation, but was transferred from the CVB3-infected, ER stressed myocardiocytes via soluble molecules in a TLR2, 4-independent way. In the present study, we reported that the transmissible ER stress from the infected myocardiocytes to macrophages could augment the pro-inflammatory responses and promoted the pathogenesis of viral myocarditis. Blocking ER stress transmission, instead of inhibiting its initiation, may represent novel therapeutic strategies against viral myocarditis.
Marine Streptomyces sp. derived antimycin analogues suppress HeLa cells via depletion HPV E6/E7 mediated by ROS-dependent ubiquitin–proteasome system
Authors: Zhang Weiyi , Che Qian , Tan Hongsheng , Qi Xin , Li Jing , Li Dehai , Gu Qianqun , Zhu Tianjiao , Liu Ming
Published: February 2017

Four new antimycin alkaloids (1–4) and six related known analogs (5–10) were isolated from the culture of a marine derivedStreptomycessp. THS-55, and their structures were elucidated by extensive spectroscopic analysis. All of the compounds exhibited potent cytotoxicityin vitroagainst HPV-transformed HeLa cell line. Among them, compounds6–7were derived as natural products for the first time, and compound5(NADA) showed the highest potency. NADA inhibited the proliferation, arrested cell cycle distribution, and triggered apoptosis in HeLa cancer cells. Our molecular mechanic studies revealed NADA degraded the levels of E6/E7 oncoproteins through ROS-mediated ubiquitin-dependent proteasome system activation. This is the first report that demonstrates antimycin alkaloids analogue induces the degradation of high-risk HPV E6/E7 oncoproteins and finally induces apoptosis in cervical cancer cells. The present work suggested that these analogues could serve as lead compounds for the development of HPV-infected cervical cancer therapeutic agents, as well as research tools for the study of E6/E7 functions.
ePro-ClearSee: a simple immunohistochemical method that does not require sectioning of plant samples
Authors: Nagaki Kiyotaka , Yamaji Naoki , Murata Minoru
Published: February 2017

Investigations into the epigenetic status of individual cells within tissues can produce both epigenetic data for different cell types and positional information of the cells. Thus, these investigations are important for understanding the intra- and inter-cellular control systems of developmental and environmental responses in plants. However, a simple method to detect epigenetic modifications of individual cells in plant tissues is not yet available because detection of the modifications requires immunohistochemistry using specific antibodies. In this study, we developed a simple immunohistochemical method that does not require sectioning to investigate epigenetic modifications. This method uses a clearing system to detect methylated histones, acetylated histones, methylated DNA and/or centromeric histone H3 variants. Analyses of four dicots and five monocots indicated that this method provides a universal technique to investigate epigenetic modifications in diverse plant species.
Engineering a pH responsive pore forming protein
Authors: Kisovec Matic , Rezelj Saša , Knap Primož , Cajnko Miša Mojca , Caserman Simon , Flašker Ajda , Žnidaršič Nada , Repič Matej , Mavri Janez , Ruan Yi , Scheuring Simon , Podobnik Marjetka , Anderluh Gregor
Published: February 2017

Listeriolysin O (LLO) is a cytolysin capable of forming pores in cholesterol-rich lipid membranes of host cells. It is conveniently suited for engineering a pH-governed responsiveness, due to a pH sensor identified in its structure that was shown before to affect its stability. Here we introduced a new level of control of its hemolytic activity by making a variant with hemolytic activity that was pH-dependent. Based on detailed structural analysis coupled with molecular dynamics and mutational analysis, we found that the bulky side chain of Tyr406 allosterically affects the pH sensor. Molecular dynamics simulation further suggested which other amino acid residues may also allosterically influence the pH-sensor. LLO was engineered to the point where it can, in a pH-regulated manner, perforate artificial and cellular membranes. The single mutant Tyr406Ala bound to membranes and oligomerized similarly to the wild-type LLO, however, the final membrane insertion step was pH-affected by the introduced mutation. We show that the mutant toxin can be activated at the surface of artificial membranes or living cells by a single wash with slightly acidic pH buffer. Y406A mutant has a high potential in development of novel nanobiotechnological applications such as controlled release of substances or as a sensor of environmental pH.
Cofactor recycling for co-production of 1,3-propanediol and glutamate by metabolically engineered Corynebacterium glutamicum
Authors: Huang Jinhai , Wu Yao , Wu Wenjun , Zhang Ye , Liu Dehua , Chen Zhen
Published: February 2017

Production of 1,3-propanediol (1,3-PDO) from glycerol is a promising route toward glycerol biorefinery. However, the yield of 1,3-PDO is limited due to the requirement of NADH regeneration via glycerol oxidation process, which generates large amounts of undesired byproducts. Glutamate fermentation by Corynebacterium glutamicum is an important oxidation process generating excess NADH. In this study, we proposed a novel strategy to couple the process of 1,3-PDO synthesis with glutamate production for cofactor regeneration. With the optimization of 1,3-PDO synthesis route, C. glutamicum can efficiently convert glycerol into 1,3-PDO with the yield of ~ 1.0 mol/mol glycerol. Co-production of 1,3-PDO and glutamate was also achieved which increased the yield of glutamate by 18% as compared to the control. Since 1,3-PDO and glutamate can be easily separated in downstream process, this study provides a potential green route for coupled production of 1,3-PDO and glutamate to enhance the economic viability of biorefinery process.
The earliest molecular response to stretch of insect flight muscle as revealed by fast X-ray diffraction recording
Authors: Iwamoto Hiroyuki
Published: February 2017

Small insects drive their flight muscle at frequencies up to 1,000 Hz. This remarkable ability owes to the mechanism of stretch activation. However, it remains unknown as to what sarcomeric component senses the stretch and triggers the following force generation. Here we show that the earliest structural change after a step stretch is reflected in the blinking of the 111 and 201 reflections, as observed in the fast X-ray diffraction recording from isolated bumblebee flight muscle fibers. The same signal has also been observed in live bumblebee. We demonstrate that (1) the signal responds almost concomitantly to a quick step stretch, (2) the signal grows with increasing calcium levels as the stretch-activated force does, and (3) a full 3-dimensional model demonstrates that the signal is maximized when objects having a 38.7-nm actin periodicity travel by ~20 nm along the filament axis. This is the expected displacement if myosin heads are loosely associated with actin target zones (where actin monomers are favorably oriented), and are dragged by a 1.3% stretch, which effectively causes stretch-induced activation. These results support and strengthen our proposal that the myosin head itself acts as the stretch sensor, after calcium-induced association with actin in a low-force form.