bluuebunny/crossref_metadata_2025 huggingface dataset:
Transforming growth factor β: a master regulator of the gut microbiota and immune cell interactions
Authors: Bauché David , Marie Julien C
Published: April 2017

The relationship between host organisms and their microbiota has co‐evolved towards an inter‐dependent network of mutualistic interactions. This interplay is particularly well studied in the gastrointestinal tract, where microbiota and host immune cells can modulate each other directly, as well as indirectly, through the production and release of chemical molecules and signals. In this review, we define the functional impact of transforming growth factor‐beta (TGF‐β) on this complex interplay, especially through its modulation of the activity of local regulatory T cells (Tregs), type 17 helper (Th17) cells, innate lymphoid cells (ILCs) and B cells.
Who lives in a fungus? The diversity, origins and functions of fungal endobacteria living in Mucoromycota
Authors: Bonfante Paola , Desirò Alessandro
Published: April 2017

Bacterial interactions with plants and animals have been examined for many years; differently, only with the new millennium the study of bacterial–fungal interactions blossomed, becoming a new field of microbiology with relevance to microbial ecology, human health and biotechnology. Bacteria and fungi interact at different levels and bacterial endosymbionts, which dwell inside fungal cells, provide the most intimate example. Bacterial endosymbionts mostly occur in fungi of the phylum Mucoromycota and include Betaproteobacteria (Burkhoderia-related) and Mollicutes (Mycoplasma-related). Based on phylogenomics and estimations of divergence time, we hypothesized two different scenarios for the origin of these interactions (early vs late bacterial invasion). Sequencing of the genomes of fungal endobacteria revealed a significant reduction in genome size, particularly in endosymbionts of Glomeromycotina, as expected by their uncultivability and host dependency. Similar to endobacteria of insects, the endobacteria of fungi show a range of behaviours from mutualism to antagonism. Emerging results suggest that some benefits given by the endobacteria to their plant-associated fungal host may propagate to the interacting plant, giving rise to a three-level inter-domain interaction.
Class 1 integrons are low-cost structures in Escherichia coli
Authors: Lacotte Yohann , Ploy Marie-Cécile , Raherison Sophie
Published: April 2017

Resistance integrons are bacterial genetic platforms that can capture and express antibiotic resistance genes embedded within gene cassettes. The capture and shuffling of gene cassettes are mediated by the integrase IntI, the expression of which is regulated by the SOS response in Escherichia coli. Gene cassettes are expressed from a common Pc promoter. Despite the clinical and environmental relevance of integrons, the selective forces responsible for their evolution and maintenance are poorly understood. Here, we conducted pairwise competition experiments in order to assess the fitness cost of class 1 integrons in E. coli. We found that integrons are low-cost structures and that their cost is further reduced by their tight regulation. We show that the SOS response prevents the expression of costly integrases whose cost is activity dependent. Thus, when an integron is repressed, its cost depends mostly on the expression of its gene cassettes array and increases with Pc strength and the number of cassettes in the array. Furthermore, different cassettes have different costs. Lastly, we showed that subinhibitory antibiotic concentrations promoted the selection of integron-carrying bacteria, especially those with a strong Pc promoter. These results provide new insights into the evolutionary dynamics of integron-carrying bacterial populations.
Defective Gpsm2/Gαi3 signalling disrupts stereocilia development and growth cone actin dynamics in Chudley-McCullough syndrome
Authors: Mauriac Stephanie A. , Hien Yeri E. , Bird Jonathan E. , Carvalho Steve Dos-Santos , Peyroutou Ronan , Lee Sze Chim , Moreau Maite M. , Blanc Jean-Michel , Gezer Aysegul , Medina Chantal , Thoumine Olivier , Beer-Hammer Sandra , Friedman Thomas B. , Rüttiger Lukas , Forge Andrew , Nürnberg Bernd , Sans Nathalie , Montcouquiol Mireille
Published: April 2017

Mutations inGPSM2cause Chudley-McCullough syndrome (CMCS), an autosomal recessive neurological disorder characterized by early-onset sensorineural deafness and brain anomalies. Here, we show that mutation of the mouse orthologue ofGPSM2affects actin-rich stereocilia elongation in auditory and vestibular hair cells, causing deafness and balance defects. The G-protein subunit Gαi3, a well-documented partner of Gpsm2, participates in the elongation process, and its absence also causes hearing deficits. We show that Gpsm2 defines an ∼200 nm nanodomain at the tips of stereocilia and this localization requires the presence of Gαi3, myosin 15 and whirlin. Using single-molecule tracking, we report that loss ofGpsm2leads to decreased outgrowth and a disruption of actin dynamics in neuronal growth cones. Our results elucidate the aetiology of CMCS and highlight a new molecular role for Gpsm2/Gαi3in the regulation of actin dynamics in epithelial and neuronal tissues.
Electrical spin injection and detection in molybdenum disulfide multilayer channel
Authors: Liang Shiheng , Yang Huaiwen , Renucci Pierre , Tao Bingshan , Laczkowski Piotr , Mc-Murtry Stefan , Wang Gang , Marie Xavier , George Jean-Marie , Petit-Watelot Sébastien , Djeffal Abdelhak , Mangin Stéphane , Jaffrès Henri , Lu Yuan
Published: April 2017

Molybdenum disulfide has recently emerged as a promising two-dimensional semiconducting material for nano-electronic, opto-electronic and spintronic applications. However, the demonstration of an electron spin transport through a semiconducting MoS2 channel remains challenging. Here we show the evidence of the electrical spin injection and detection in the conduction band of a multilayer MoS2 semiconducting channel using a two-terminal spin-valve configuration geometry. A magnetoresistance around 1% has been observed through a 450 nm long, 6 monolayer thick MoS2 channel with a Co/MgO tunnelling spin injector and detector. It is found that keeping a good balance between the interface resistance and channel resistance is mandatory for the observation of the two-terminal magnetoresistance. Moreover, the electron spin-relaxation is found to be greatly suppressed in the multilayer MoS2 channel with an in-plane spin polarization. The long spin diffusion length (approximately ∼235 nm) could open a new avenue for spintronic applications using multilayer transition metal dichalcogenides.
Easy access to nucleophilic boron through diborane to magnesium boryl metathesis
Authors: Pécharman Anne-Frédérique , Colebatch Annie L. , Hill Michael S. , McMullin Claire L. , Mahon Mary F. , Weetman Catherine
Published: April 2017

Organoboranes are some of the most synthetically valuable and widely used intermediates in organic and pharmaceutical chemistry. Their synthesis, however, is limited by the behaviour of common boron starting materials as archetypal Lewis acids such that common routes to organoboranes rely on the reactivity of boron as an electrophile. While the realization of convenient sources of nucleophilic boryl anions would open up a wealth of opportunity for the development of new routes to organoboranes, the synthesis of current candidates is generally limited by a need for highly reducing reaction conditions. Here, we report a simple synthesis of a magnesium boryl through the heterolytic activation of the B–B bond of bis(pinacolato)diboron, which is achieved by treatment of an easily generated magnesium diboranate complex with 4-dimethylaminopyridine. The magnesium boryl is shown to act as an unambiguous nucleophile through its reactions with iodomethane, benzophenone and N,N′-di-isopropyl carbodiimide and by density functional theory.
The epidemiology, radiology and biological characteristics of interval breast cancers in population mammography screening
Authors: Houssami Nehmat , Hunter Kylie
Published: April 2017

An interval breast cancer is a cancer that emerges following a negative mammographic screen. This overview describes the epidemiology, and the radiological and biological characteristics of interval breast cancers in population mammography screening. Notwithstanding possible differences in ascertainment of interval breast cancers, there was broad variability in reported interval breast cancer rates (range 7.0 to 49.3 per 10,000 screens) reflecting heterogeneity in underlying breast cancer rates, screening rounds (initial or repeat screens), and the length and phase of the inter-screening interval. The majority of studies (based on biennial screening) reported interval breast cancer rates in the range of 8.4 to 21.1 per 10,000 screens spanning the two-year interval with the larger proportion occurring in the second year. Despite methodological limitations inherent in radiological surveillance (retrospective mammographic review) of interval breast cancers, this form of surveillance consistently reveals that the majority of interval cancers represent either true interval or occult cancers that were not visible on the index mammographic screen; approximately 20–25% of interval breast cancers are classified as having been missed (false-negatives). The biological characteristics of interval breast cancers show that they have relatively worse tumour prognostic characteristics and biomarker profile, and also survival outcomes, than screen-detected breast cancers; however, they have similar characteristics and prognosis as breast cancers occurring in non-screened women. There was limited evidence on the effect on interval breast cancer frequency and outcomes following transition from film to digital mammography screening.
Reliably estimating prevalences of atopic children: an epidemiological study in an extensive and representative primary care database
Authors: Pols David H. J. , Nielen Mark. M. J. , Korevaar Joke C. , Bindels Patrick J. E. , Bohnen Arthur M.
Published: April 2017

Electronic health records stored in primary care databases might be a valuable source to study the epidemiology of atopic disorders and their impact on health-care systems and costs. However, the prevalence of atopic disorders in such databases varies considerably and needs to be addressed. For this study, all children aged 0–18 years listed in a representative primary care database in the period 2002–2014, with sufficient data quality, were selected. The effects of four different strategies on the prevalences of atopic disorders were examined: (1) the first strategy examined the diagnosis as recorded in the electronic health records, whereas the (2) second used additional requirements (i.e., the patient had at least two relevant consultations and at least two relevant prescriptions). Strategies (3) and (4) assumed the atopic disorders to be chronic based on strategy 1 and 2, respectively. When interested in cases with a higher probability of a clinically relevant disorder, strategy 2 yields a realistic estimation of the prevalence of atopic disorders derived from primary care data. Using this strategy, of the 478,076 included children, 28,946 (6.1%) had eczema, 29,182 (6.1%) had asthma, and 28,064 (5.9%) had allergic rhinitis; only 1251 (0.3%) children had all three atopic disorders. Prevalence rates are highly dependent on the clinical atopic definitions used. The strategy using cases with a higher probability of clinically relevant cases, yields realistic prevalences to establish the impact of atopic disorders on health-care systems. However, studies are needed to solve the problem of identifying atopic disorders that are missed or misclassified.
High resolution neutron Larmor diffraction using superconducting magnetic Wollaston prisms
Authors: Li Fankang , Feng Hao , Thaler Alexander N. , Parnell Steven R. , Hamilton William A. , Crow Lowell , Yang Wencao , Jones Amy B. , Bai Hongyu , Matsuda Masaaki , Baxter David V. , Keller Thomas , Fernandez-Baca Jaime A. , Pynn Roger
Published: April 2017

The neutron Larmor diffraction technique has been implemented using superconducting magnetic Wollaston prisms in both single-arm and double-arm configurations. Successful measurements of the coefficient of thermal expansion of a single-crystal copper sample demonstrates that the method works as expected. The experiment involves a new method of tuning by varying the magnetic field configurations in the device and the tuning results agree well with previous measurements. The difference between single-arm and double-arm configurations has been investigated experimentally. We conclude that this measurement benchmarks the applications of magnetic Wollaston prisms in Larmor diffraction and shows in principle that the setup can be used for inelastic phonon line-width measurements. The achievable resolution for Larmor diffraction is comparable to that using Neutron Resonance Spin Echo (NRSE) coils. The use of superconducting materials in the prisms allows high neutron polarization and transmission efficiency to be achieved.
Lack of association of C3 gene with uveitis: additional insights into the genetic profile of uveitis regarding complement pathway genes
Authors: Yang Ming Ming , Wang Jun , Dong Li , Kong De Ju , Teng Yan , Liu Ping , Fan Jiao Jie , Yu Xu Hui
Published: April 2017

Uveitis is a devastating ocular disease that causes blindness. Our previous studies have achieved great advancements in depicting the genetic profiles of uveitis regarding complement pathway genes. This study aimed to provide additional insights into this interest by testing the “central” factor of the complement system, C3 gene variants, in two uveitis entities. Eight haplotype-tagging SNPs of C3 gene were genotyped in 141 anterior uveitis (AU), 158 non-infectious intermediate and posterior uveitis (NIPU) and 293 controls. The results showed that none of the tagging SNPs had a significant association with uveitis (P > 0.05), either in the global uveitis or subtypes. Although rs428453 showed a nominal association with NIPU subtype in the recessive model (P = 0.042), the P value could not withstand the Bonferroni correction (Pcorr > 0.05). Stratification analyses according to HLA-B27 status and correlation analysis still did not find any significant interactions or genetic markers regarding AU. Logistic regression analysis also revealed no gender-related epistatic effects of C3 on uveitis. Two haplotype blocks were defined across the C3 locus but neither of them was significantly associated with uveitis or subtypes. This study shows no significant association of the C3 gene with uveitis, suggesting C3 confers either no or limited risk for uveitis susceptibility.
MIEF1/2 function as adaptors to recruit Drp1 to mitochondria and regulate the association of Drp1 with Mff
Authors: Yu Rong , Liu Tong , Jin Shao-Bo , Ning Chenfei , Lendahl Urban , Nistér Monica , Zhao Jian
Published: April 2017

Mitochondrial dynamics is a fundamental cellular process and recruitment of Drp1 to mitochondria is an essential step in mitochondrial fission. Mff and MIEF1/2 (MiD51/49) serve as key receptors for recruitment of Drp1 to mitochondria in mammals. However, if and how these receptors work together in mitochondrial fission is poorly understood. Here we show that MIEFs interact with both Drp1 and Mff on the mitochondrial surface and serve as adaptors linking Drp1 and Mff together in a trimeric Drp1-MIEF-Mff complex. Thus, MIEFs can regulate the interaction between Drp1 and Mff, and also Mff-induced Drp1 accumulation on mitochondria. It is shown that loss of endogenous MIEFs severely impairs these processes. Additionally, in cells depleted of endogenous MIEF1/2, high levels of exogenous MIEFs sequester Drp1 on the mitochondrial surface, resulting in mitochondrial elongation, whereas low-to-moderate levels of MIEFs promote mitochondrial fission, leading to mitochondrial fragmentation. In sum, the data suggest that MIEFs and Mff work coordinately in Drp1-mediated mitochondrial fission and that the level of MIEF1/2 relative to Mff sets the balance between mitochondrial fission and fusion.
Establishment of a novel human lymphoblastic cell strain with the long arm of chromosome 11 aberration without MLL rearrangement
Authors: Wang Qian , Zhuang Lin , Li Pei , Niu Qiang , Zhu Ping , He Miao-Xia , Jiang Hui , Liu Chang-Cheng , Wang Min-Jun , Chen Li , Cheng Hui , Ma Yan , Hu Xiao-Xia , Hu Yi-Ping , Xu Xiao-Ping
Published: April 2017

At present, all cell strains derived from acute lymphoblastic leukemia (ALL) patients with the long arm of chromosome 11 aberration are accompanied with mixed lineage leukemia (MLL) gene rearrangement. In this study, we established a permanent ALL cell strain CHH-1 with the long arm of chromosome 11 aberration and withoutMLLrearrangement, hoping that it could be used for the research of ALL with such genetic abnormality. CHH-1 cell strain was certified through morphology, immunophenotype, genetics and immunoglobulin (Ig) gene rearrangement analysis. Cell characteristics including tumorigenic ability, semisolid colony forming ability, telomerase activity, autocrine and invasion were further detected. Cells were with an add(11)(q23) structural abnormality withoutMLLrearrangement, and were consistent with the genetic abnormality of the patient. In addition, these cells had features of tumor-forming ability, high colony forming capacity, unique cytokine autocrine mode, high telomerase activity, and high invasion ability. CHH-1 may prove to be a useful cell model for the research of human leukemia with genetic aberration in chromosome 11, and help explore the role of such genetic abnormality in the pathogenesis, progression and prognosis of ALL, and in developing new target drugs.
Identification of exosomes and its signature miRNAs of male and female Cynoglossus semilaevis
Authors: Sun Zhanpeng , Hao Tong , Tian Jinze
Published: April 2017

Exosomes are small membrane particles which are widely found in various cell lines and physiological fluids in mammalian. MicroRNAs (miRNAs) enclosed in exosomes have been identified as proper signatures for many diseases and response to therapies. However, the composition of exosomes and enclosed miRNAs in fishes has not been investigated. Cynoglossus semilaevis is an important commercial flatfish with ambiguous distinction between males and females before sex maturation, which leads to screening difficulty in reproduction and cultivation. An effective detection method was required for sex differentiation of C. semilaevis. In this work, we successfully identified exosomes in C. semilaevis serum. The analysis of nucleotide composition showed that miRNA dominated in exosomes. Thereafter the miRNA profiles in exosomes from males and females were sequenced and compared to identify the signature miRNAs corresponding to sex differentiation. The functions of signature miRNAs were analyzed by target matching and annotation. Furthermore, 7 miRNAs with high expression in males were selected from signature miRNAs as the markers for sex identification with their expression profiles verified by real time quantitative PCR. Exosomes were first found in fish serum in this work. Investigation of marker miRNAs supplies an effective index for the filtration of male and female C. semilaevis in cultivation.
Fungal volatile compounds induce production of the secondary metabolite Sodorifen in Serratia plymuthica PRI-2C
Authors: Schmidt Ruth , Jager Victor de , Zühlke Daniela , Wolff Christian , Bernhardt Jörg , Cankar Katarina , Beekwilder Jules , Ijcken Wilfred van , Sleutels Frank , Boer Wietse de , Riedel Katharina , Garbeva Paolina
Published: April 2017

The ability of bacteria and fungi to communicate with each other is a remarkable aspect of the microbial world. It is recognized that volatile organic compounds (VOCs) act as communication signals, however the molecular responses by bacteria to fungal VOCs remain unknown. Here we perform transcriptomics and proteomics analyses of Serratia plymuthica PRI-2C exposed to VOCs emitted by the fungal pathogen Fusarium culmorum. We find that the bacterium responds to fungal VOCs with changes in gene and protein expression related to motility, signal transduction, energy metabolism, cell envelope biogenesis, and secondary metabolite production. Metabolomic analysis of the bacterium exposed to the fungal VOCs, gene cluster comparison, and heterologous co-expression of a terpene synthase and a methyltransferase revealed the production of the unusual terpene sodorifen in response to fungal VOCs. These results strongly suggest that VOCs are not only a metabolic waste but important compounds in the long-distance communication between fungi and bacteria.
Predicting neurological Adverse Drug Reactions based on biological, chemical and phenotypic properties of drugs using machine learning models
Authors: Jamal Salma , Goyal Sukriti , Shanker Asheesh , Grover Abhinav
Published: April 2017

Adverse drug reactions (ADRs) have become one of the primary reasons for the failure of drugs and a leading cause of deaths. Owing to the severe effects of ADRs, there is an urgent need for the generation of effective models which can accurately predict ADRs during early stages of drug development based on integration of various features of drugs. In the current study, we have focused on neurological ADRs and have used various properties of drugs that include biological properties (targets, transporters and enzymes), chemical properties (substructure fingerprints), phenotypic properties (side effects (SE) and therapeutic indications) and a combinations of the two and three levels of features. We employed relief-based feature selection technique to identify relevant properties and used machine learning approach to generated learned model systems which would predict neurological ADRs prior to preclinical testing. Additionally, in order to explain the efficiency and applicability of the models, we tested them to predict the ADRs for already existing anti-Alzheimer drugs and uncharacterized drugs, respectively in side effect resource (SIDER) database. The generated models were highly accurate and our results showed that the models based on chemical (accuracy 93.20%), phenotypic (accuracy 92.41%) and combination of three properties (accuracy 94.18%) were highly accurate while the models based on biological properties (accuracy 82.11%) were highly informative.
MMP9 integrates multiple immunoregulatory pathways that discriminate high suppressive activity of human mesenchymal stem cells
Authors: Lavini-Ramos Carolina , Silva Hernandez Moura , Soares-Schanoski Alessandra , Monteiro Sandra Maria , Ferreira Ludmila Rodrigues Pinto , Pacanaro Ana Paula , Gomes Samirah , Batista Janaína , Faé Kellen , Kalil Jorge , Coelho Verônica
Published: April 2017

The mechanisms underlying mesenchymal stem cells’ (MSC) suppressive potency are largely unknown. We here show that highly suppressive human adipose tissue-derived MSC (AdMSC) display and induce a differential immunologic profile, upon ongoing AdMSC suppressive activity, promoting: (i) early correlated inhibition of IFN-γ and TNF-α production, along IL-10 increase, (ii) CD73+Foxp3+Treg subset expansion, and (iii) specific correlations between gene expression increases, such as: MMP9 correlated with CCL22, TNF, FASL, RUNX3, and SEMAD4 in AdMSC and, in T cells, MMP9 upregulation correlated with CCR4, IL4 and TBX21, among others, whereas MMP2 correlated with BCL2 and LRRC31. MMP9 emerged as an integrating molecule for both AdMSC and T cells in molecular networks built with our gene expression data, and we confirmed upregulation of MMP9 and MMP2 at the protein level, in AdMSC and T cells, respectively. MMP2/9 inhibition significantly decreased AdMSC suppressive effect, confirming their important role in suppressive acitivity. We conclude that MMP9 and 2 are robust new players involved in human MSC immunoregulatory mechanisms, and the higher suppressive activity correlates to their capacity to trigger a coordinated action of multiple specific molecules, mobilizing various immunoregulatory mechanisms.
Fossil climbing perch and associated plant megafossils indicate a warm and wet central Tibet during the late Oligocene
Authors: Wu Feixiang , Miao Desui , Chang Mee-mann , Shi Gongle , Wang Ning
Published: April 2017

Understanding the Tibetan Plateau’s palaeogeography and palaeoenvironment is critical for reconstructing Asia’s climatic history; however, aspects of the plateau’s uplift history remain unclear. Here, we report a fossil biota that sheds new light on these issues. It comprises a fossil climbing perch (Anabantidae) and a diverse subtropical fossil flora from the Chattian (late Oligocene) of central Tibet. The fish, Eoanabas thibetana gen. et sp. nov., is inferred to be closely related to extant climbing perches from tropical lowlands in south Asia and sub-Saharan Africa. It has osteological correlates of a labyrinth organ, which in extant climbing perches gives them the ability to breathe air to survive warm, oxygen-poor stagnant waters or overland excursion under moist condition. This indicates that Eoanabas likewise lived in a warm and humid environment as suggested by the co-existing plant assemblage including palms and golden rain trees among others. As a palaeoaltimeter, this fossil biota suggests an elevation of ca. 1,000 m. These inferences conflict with conclusions of a high and dry Tibet claimed by some recent and influential palaeoaltimetry studies. Our discovery prompts critical re-evaluation of prevailing uplift models of the plateau and their temporal relationships with the Cenozoic climatic changes.
Interplay of buried histidine protonation and protein stability in prion misfolding
Authors: Malevanets Anatoly , Chong P. Andrew , Hansen D. Flemming , Rizk Paul , Sun Yulong , Lin Hong , Muhandiram Ranjith , Chakrabartty Avi , Kay Lewis E. , Forman-Kay Julie D. , Wodak Shoshana J.
Published: April 2017

Misofolding of mammalian prion proteins (PrP) is believed to be the cause of a group of rare and fatal neurodegenerative diseases. Despite intense scrutiny however, the mechanism of the misfolding reaction remains unclear. We perform nuclear Magnetic Resonance and thermodynamic stability measurements on the C-terminal domains (residues 90–231) of two PrP variants exhibiting different pH-induced susceptibilities to aggregation: the susceptible hamster prion (GHaPrP) and its less susceptible rabbit homolog (RaPrP). The pKa of histidines in these domains are determined from titration experiments, and proton-exchange rates are measured at pH 5 and pH 7. A single buried highly conserved histidine, H187/H186 in GHaPrP/RaPrP, exhibited a markedly down shifted pKa ~5 for both proteins. However, noticeably larger pH-induced shifts in exchange rates occur for GHaPrP versus RaPrP. Analysis of the data indicates that protonation of the buried histidine destabilizes both PrP variants, but produces a more drastic effect in the less stable GHaPrP. This interpretation is supported by urea denaturation experiments performed on both PrP variants at neutral and low pH, and correlates with the difference in disease susceptibility of the two species, as expected from the documented linkage between destabilization of the folded state and formation of misfolded and aggregated species.
Active Mediation of Plasmon Enhanced Localized Exciton Generation, Carrier Diffusion and Enhanced Photon Emission
Authors: Haq Sharmin , Addamane Sadhvikas , Kafle Bijesh , Huang Danhong , Balakrishnan Ganesh , Habteyes Terefe G.
Published: April 2017

Understanding the enhancement of charge carrier generation and their diffusion is imperative for improving the efficiency of optoelectronic devices particularly infrared photodetectors that are less developed than their visible counterpart. Here, using gold nanorods as model plasmonic systems, InAs quantum dots (QDs) embedded in an InGaAs quantum well as an emitter, and GaAs as an active mediator of surface plasmons for enhancing carrier generation and photon emission, the distance dependence of energy transfer and carrier diffusion have been investigated both experimentally and theoretically. Analysis of the QD emission enhancement as a function of distance reveals a Förster radius of 3.85 ± 0.15 nm, a near-field decay length of 4.8 ± 0.1 nm and an effective carrier diffusion length of 64.0 ± 3.0 nm. Theoretical study of the temporal-evolution of the electron-hole occupation number of the excited states of the QDs indicates that the emission enhancement trend is determined by the carrier diffusion and capture rates.
Super-tunable, broadband up-conversion of a high-power CW laser in an engineered nonlinear crystal
Authors: Bostani Ameneh , Tehranchi Amirhossein , Kashyap Raman
Published: April 2017

A specially-designed chirped periodically poled lithium niobate nonlinear crystal was fabricated with a phase-matching bandwidth as large as 50 nm for sum frequency generation to operate at room and higher temperatures. This device also benefits from insensitivity to laser frequency drift and fine alignment. The loosely-focused beam position of a high-power CW laser at around 1550 nm is optimized within the grating for maximum up-conversion efficiency, to realize a super-tunable source in the range of 770–778 nm by tuning a narrowband control signal over 30 nm in the communication band. This device is demonstrated to be fully phased-matched simultaneously for both second-order nonlinear up-conversion processes, namely second harmonic generation and sum frequency generation. The measurement of the generated sum-frequency power versus wavelength agrees well with the theory. The device allows for the creation of tunable broadband CW sources at shorter wavelengths with potentially high power.
Endothelial and Astrocytic Support by Human Bone Marrow Stem Cell Grafts into Symptomatic ALS Mice towards Blood-Spinal Cord Barrier Repair
Authors: Garbuzova-Davis Svitlana , Kurien Crupa , Thomson Avery , Falco Dimitri , Ahmad Sohaib , Staffetti Joseph , Steiner George , Abraham Sophia , James Greeshma , Mahendrasah Ajay , Sanberg Paul R. , Borlongan Cesario V.
Published: April 2017

Vascular pathology, including blood-CNS barrier (B-CNS-B) damage via endothelial cell (EC) degeneration, is a recently recognized hallmark of Amyotrophic Lateral Sclerosis (ALS) pathogenesis. B-CNS-B repair may be a new therapeutic approach for ALS. This study aimed to determine effects of transplanted unmodified human bone marrow CD34+ (hBM34+) cells into symptomatic G93A mice towards blood-spinal cord barrier (BSCB) repair. Thirteen weeks old G93A mice intravenously received one of three different doses of hBM34+ cells. Cell-treated, media-treated, and control mice were euthanized at 17 weeks of age. Immunohistochemical (anti-human vWF, CD45, GFAP, and Iba-1) and motor neuron histological analyses were performed in cervical and lumbar spinal cords. EB levels in spinal cord parenchyma determined capillary permeability. Transplanted hBM34+ cells improved behavioral disease outcomes and enhanced motor neuron survival, mainly in high-cell-dose mice. Transplanted cells differentiated into ECs and engrafted within numerous capillaries. Reduced astrogliosis, microgliosis, and enhanced perivascular end-feet astrocytes were also determined in spinal cords, mostly in high-cell-dose mice. These mice also showed significantly decreased parenchymal EB levels. EC differentiation, capillary engraftment, reduced capillary permeability, and re-established perivascular end-feet astrocytes in symptomatic ALS mice may represent BSCB repair processes, supporting hBM34+ cell transplantation as a future therapeutic strategy for ALS patients.
Defect-Induced Luminescence Quenching vs. Charge Carrier Generation of Phosphorus Incorporated in Silicon Nanocrystals as Function of Size
Authors: Hiller Daniel , López-Vidrier Julian , Gutsch Sebastian , Zacharias Margit , Nomoto Keita , König Dirk
Published: April 2017

Phosphorus doping of silicon nanostructures is a non-trivial task due to problems with confinement, self-purification and statistics of small numbers. Although P-atoms incorporated in Si nanostructures influence their optical and electrical properties, the existence of free majority carriers, as required to control electronic properties, is controversial. Here, we correlate structural, optical and electrical results of size-controlled, P-incorporating Si nanocrystals with simulation data to address the role of interstitial and substitutional P-atoms. Whereas atom probe tomography proves that P-incorporation scales with nanocrystal size, luminescence spectra indicate that even nanocrystals with several P-atoms still emit light. Current-voltage measurements demonstrate that majority carriers must be generated by field emission to overcome the P-ionization energies of 110–260 meV. In absence of electrical fields at room temperature, no significant free carrier densities are present, which disproves the concept of luminescence quenching via Auger recombination. Instead, we propose non-radiative recombination via interstitial-P induced states as quenching mechanism. Since only substitutional-P provides occupied states near the Si conduction band, we use the electrically measured carrier density to derive formation energies of ~400 meV for P-atoms on Si nanocrystal lattice sites. Based on these results we conclude that ultrasmall Si nanovolumes cannot be efficiently P-doped.
Hydrogen sulfide toxicity inhibits primary root growth through the ROS-NO pathway
Authors: Zhang Ping , Luo Qiong , Wang Ruling , Xu Jin
Published: April 2017

High concentrations of hydrogen sulfide (H2S) are toxic to plants and inhibit their growth. Previous research indicated that high concentrations of H2S modulate the root system architecture (RSA) by affecting auxin transport; however, the signaling pathway underlying this process remains unclear. Here, we investigated the effects of exogenous sodium hydrosulfide (NaHS), an H2S donor, on primary root (PR) growth in Arabidopsis using pharmacological, physiological, and genetic approaches. H2S toxicity repressed PR growth by triggering a signal transduction pathway involving reactive oxygen species (ROS) accumulation, MITOGEN-ACTIVATED PROTEIN KINASE 6 (MPK6) activation, and nitric oxide (NO) production. Respiratory burst oxidase homolog mutants and an NO synthase mutant were less sensitive to NaHS, suggesting that both ROS and NO mediate the inhibitory effects of H2S on PR growth. We found that exogenous H2S-activated ROS production was required for NO generation and that MPK6 mediated H2S-induced NO production. MPK6 was shown to function downstream of ROS and upstream of NO. Finally, we demonstrated that exogenous H2S repressed the distribution of auxin and reduced the meristematic cell division potential in root tips, and NO was involved in this process.
Augmentation of working memory training by transcranial direct current stimulation (tDCS)
Authors: Ruf Steffen Philipp , Fallgatter Andreas J. , Plewnia Christian
Published: April 2017

Transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex (dlPFC) can modulate working memory (WM) performance. However, evidence regarding the enhancement of WM training, its sustainability and transferability is ambiguous. Since WM functioning appears to be lateralized in respect to stimulus characteristics, this study examined the difference between task-congruent (spatial-right, verbal-left), task-incongruent (spatial-left, verbal-right) and sham tDCS in regards to the efficacy of WM training. In a randomized, sham-controlled experiment, 71 healthy adults trained on a spatial or verbal adaptive n-back task. After a baseline session, anodal or sham tDCS (1 mA) to the right or left dlPFC was applied during the next three training sessions. Sustainability of training gains and near-transfer (verbal or spatial 3-back task) were tested in a fourth training and a follow-up session. Compared to sham stimulation, we found a steeper learning curve when WM training was combined with task-congruent tDCS. This advantage was also present compared to task-incongruent tDCS. Moreover, these effects lasted for up to nine months and transferred to the respective untrained task. These long-lasting, transferable, task-specific effects demonstrate a behaviorally relevant and sustainable facilitation of neuroplastic processes by tDCS that could be harnessed for the treatment of disorders associated with deficient WM.
Reply to ‘Comments on “Evidence of the hydrogen release mechanism in bulk MgH2”’
Authors: Nogita Kazuhiro , Tran Xuan Q. , Yamamoto Tomokazu , Tanaka Eishi , McDonald Stuart D. , Gourlay Christopher M. , Yasuda Kazuhiro , Matsumura Syo
Published: April 2017

In a comment on our Article “Evidence of the hydrogen release mechanism in bulk MgH2”, Surrey et al. assert that the MgH2 sample we studied was not MgH2 at any time but rather MgO; and that the transformation we observed was the formation of Kirkendall voids due to the outward diffusion of Mg. We address these issues in this reply.
BMP6 Regulates Proliferation and Apoptosis of Human Sertoli Cells Via Smad2/3 and Cyclin D1 Pathway and DACH1 and TFAP2A Activation
Authors: Wang Hong , Yuan Qingqing , Sun Min , Niu Minghui , Wen Liping , Fu Hongyong , Zhou Fan , Chen Zheng , Yao Chencheng , Hou Jingmei , Shen Ruinan , Lin Qisheng , Liu Wenjie , Jia Ruobing , Li Zheng , He Zuping
Published: April 2017

Sertoli cells are essential for regulating normal spermatogenesis. However, the mechanisms underlying human Sertoli cell development remain largely elusive. Here we examined the function and signaling pathways of BMP6 in regulating human Sertoli cells. RT-PCR, immunocytochemistry and Western blots revealed that BMP6 and its multiple receptors were expressed in human Sertoli cells. CCK-8 and EDU assays showed that BMP6 promoted the proliferation of Sertoli cells. Conversely, BMP6 siRNAs inhibited the division of these cells. Annexin V/PI assay indicated that BMP6 reduced the apoptosis in human Sertoli cells, whereas BMP6 knockdown assumed reverse effects. BMP6 enhanced the expression levels of ZO1, SCF, GDNF and AR in human Sertoli cells, and ELISA assay showed an increase of SCF by BMP6 and a reduction by BMP6 siRNAs. Notably, Smad2/3 phosphorylation and cyclin D1 were enhanced by BMP6 and decreased by BMP6 siRNAs in human Sertoli cells. The levels of DACH1 and TFAP2A were increased by BMP6 and reduced by BMP6 siRNAs, and the growth of human Sertoli cells was inhibited by these siRNAs. Collectively, these results suggest that BMP6 regulates the proliferation and apoptosis of human Sertoli cells via activating the Smad2/3/cyclin D1 and DACH1 and TFAP2A pathway.
Calcium oxalate crystals and oxalate induce an epithelial-to-mesenchymal transition in the proximal tubular epithelial cells: Contribution to oxalate kidney injury
Authors: Convento Marcia Bastos , Pessoa Edson Andrade , Cruz Edgar , da Glória Maria Aparecida , Schor Nestor , Borges Fernanda Teixeira
Published: April 2017

TGF-β1 is the main mediator of epithelial-to-mesenchymal transition (EMT). Hyperoxaluria induces crystalluria, interstitial fibrosis, and progressive renal failure. This study analyzed whether hyperoxaluria is associated with TGF-β1 production and kidney fibrosis in mice and if oxalate or calcium oxalate (CaOx) could induce EMT in proximal tubule cells (HK2) and therefore contribute to the fibrotic process. Hyperoxaluria was induced by adding hydroxyproline and ethylene glycol to the mice’s drinking water for up to 60 days. Renal function and oxalate and urinary crystals were evaluated. Kidney collagen production and TGF-β1 expression were assessed. EMT was analyzed in vitro according to TGF-β1 production, phenotypic characterization, invasion, cell migration, gene and protein expression of epithelial and mesenchymal markers. Hyperoxaluric mice showed a decrease in renal function and an increase in CaOx crystals and Ox urinary excretion. The deposition of collagen in the renal interstitium was observed. HK2 cells stimulated with Ox and CaOx exhibited a decreased expression of epithelial as well as increased expression mesenchymal markers; these cells presented mesenchymal phenotypic changes, migration, invasiveness capability and TGF-β1 production, characterizing EMT. Treatment with BMP-7 or its overexpression in HK2 cells was effective at preventing it. This mechanism may contribute to the fibrosis observed in hyperoxaluria.
A staged screening of registered drugs highlights remyelinating drug candidates for clinical trials
Authors: Eleuteri C. , Olla S. , Veroni C. , Umeton R. , Mechelli R. , Romano S. , Buscarinu MC. , Ferrari F. , Calò G. , Ristori G. , Salvetti M. , Agresti C.
Published: April 2017

There is no treatment for the myelin loss in multiple sclerosis, ultimately resulting in the axonal degeneration that leads to the progressive phase of the disease. We established a multi-tiered platform for the sequential screening of drugs that could be repurposed as remyelinating agents. We screened a library of 2,000 compounds (mainly Food and Drug Administration (FDA)-approved compounds and natural products) for cellular metabolic activity on mouse oligodendrocyte precursors (OPC), identifying 42 molecules with significant stimulating effects. We then characterized the effects of these compounds on OPC proliferation and differentiation in mouse glial cultures, and on myelination and remyelination in organotypic cultures. Three molecules, edaravone, 5-methyl-7-methoxyisoflavone and lovastatin, gave positive results in all screening tiers. We validated the results by retesting independent stocks of the compounds, analyzing their purity, and performing dose-response curves. To identify the chemical features that may be modified to enhance the compounds’ activity, we tested chemical analogs and identified, for edaravone, the functional groups that may be essential for its activity. Among the selected remyelinating candidates, edaravone appears to be of strong interest, also considering that this drug has been approved as a neuroprotective agent for acute ischemic stroke and amyotrophic lateral sclerosis in Japan.
A 3q gene signature associated with triple negative breast cancer organ specific metastasis and response to neoadjuvant chemotherapy
Authors: Qian Jun , Chen Heidi , Ji Xiangming , Eisenberg Rosana , Chakravarthy A. Bapsi , Mayer Ingrid A. , Massion Pierre P.
Published: April 2017

Triple negative breast cancers (TNBC) are aggressive tumors, with high rates of metastatic spread and targeted therapies are critically needed. We aimed to assess the prognostic and predictive value of a 3q 19-gene signature identified previously from lung cancer in a collection of 4,801 breast tumor gene expression data. The 3q gene signature had a strong association with features of aggressiveness such as high grade, hormone receptor negativity, presence of a basal-like or TNBC phenotype and reduced distant metastasis free survival. The 3q gene signature was strongly associated with lung metastasis only in TNBC (P < 0.0001, Hazard ratio (HR) 1.44, 95% confidence interval (CI), 1.31–1.60), significantly associated with brain but not bone metastasis regardless of TNBC status. The association of one 3q driver gene FXR1 with distant metastasis in TNBC (P = 0.01) was further validated by immunohistochemistry. In addition, the 3q gene signature was associated with better response to neoadjuvant chemotherapy in TNBC (P < 0.0001) but not in non-TNBC patients. Our study suggests that the 3q gene signature is a novel prognostic marker for lung and/or brain metastasis and a predictive marker for the response to neoadjuvant chemotherapy in TNBC, implying a potential role for 3q genes in the mechanism of organ-specific metastasis.
Identification of dominating factors affecting vadose zone vulnerability by a simulation method
Authors: Li Juan , Xi Beidou , Cai Wutian , Yang Yang , Jia Yongfeng , Li Xiang , Lv Yonggao , Lv Ningqing , Huan Huan , Yang Jinjin
Published: April 2017

The characteristics of vadose zone vulnerability dominating factors (VDFs) are closely related to the migration and transformation mechanisms of contaminants in the vadose zone, which directly affect the state of the contaminants percolating to the groundwater. This study analyzes the hydrogeological profile of the pore water regions in the vadose zone, and conceptualizes the vadose zone as single lithologic, double lithologic, or multi lithologic. To accurately determine how the location of the pollution source influences the groundwater, we classify the permeabilities (thicknesses) of different media into clay-layer and non-clay-layer permeabilities (thicknesses), and introduce the maximum pollution thickness. Meanwhile, the physicochemical reactions of the contaminants in the vadose zone are represented by the soil adsorption and soil degradability. The VDFs are determined from the factors and parameters in groundwater vulnerability assessment. The VDFs are identified and sequenced in simulations and a sensitivity analysis. When applied to three polluted sites in China, the method improved the weighting of factors in groundwater vulnerability assessment, and increased the reliability of predicting groundwater vulnerability to contaminants.
Introducing the ESAT-6 free IGRA, a companion diagnostic for TB vaccines based on ESAT-6
Authors: Ruhwald Morten , de Thurah Lena , Kuchaka Davis , Zaher Mostafa Rafaat , Salman Ahmed M. , Abdel-Ghaffar Abdel-Rahman , Shoukry Faten Aly , Michelsen Sascha Wilk , Soborg Bolette , Blauenfeldt Thomas , Mpagama Stellah , Hoff Søren T. , Agger Else Marie , Rosenkrands Ida , Aagard Claus , Kibiki Gibson , El-Sheikh Nabila , Andersen Peter
Published: April 2017

There is a need for an improved vaccine for tuberculosis. ESAT-6 is a cardinal vaccine antigen with unique properties and is included in several vaccine candidates in development. ESAT-6 is also the core antigen in the IFN-γ release assays (IGRA) used to diagnose latent infection, rendering IGRA tests unspecific after vaccination. This challenge has prompted the development of a companion diagnostic for ESAT-6 based vaccines, an ESAT-6 free IGRA. We screened a panel of seven potential new diagnostic antigens not recognized in BCG vaccinated individuals. Three highly recognized antigens EspC, EspF and Rv2348c were identified and combined with CFP10 in an ESAT-6 free antigen cocktail. The cocktail was prepared in a field-friendly format, lyophilized with heparin in ready-to-use vacutainer tubes. The diagnostic performance of the ESAT-6 free IGRA was determined in a cross-validation study. Compared IGRA, the ESAT-6 free IGRA induced a comparable magnitude of IFN-γ release, and the diagnostic performance was on par with Quantiferon (sensitivity 84% vs 79%; specificity 99% vs 97%). The comparable performance of the ESAT-6 free IGRA to IGRA suggests potential as companion diagnostic for ESAT-6 containing vaccines and as adjunct test for latent infection.
Multi-color electron microscopy by element-guided identification of cells, organelles and molecules
Authors: Scotuzzi Marijke , Kuipers Jeroen , Wensveen Dasha I. , de Boer Pascal , Hagen Kees W. , Hoogenboom Jacob P. , Giepmans Ben N. G.
Published: April 2017

Cellular complexity is unraveled at nanometer resolution using electron microscopy (EM), but interpretation of macromolecular functionality is hampered by the difficulty in interpreting grey-scale images and the unidentified molecular content. We perform large-scale EM on mammalian tissue complemented with energy-dispersive X-ray analysis (EDX) to allow EM-data analysis based on elemental composition. Endogenous elements, labels (gold and cadmium-based nanoparticles) as well as stains are analyzed at ultrastructural resolution. This provides a wide palette of colors to paint the traditional grey-scale EM images for composition-based interpretation. Our proof-of-principle application of EM-EDX reveals that endocrine and exocrine vesicles exist in single cells in Islets of Langerhans. This highlights how elemental mapping reveals unbiased biomedical relevant information. Broad application of EM-EDX will further allow experimental analysis on large-scale tissue using endogenous elements, multiple stains, and multiple markers and thus brings nanometer-scale ‘color-EM’ as a promising tool to unravel molecular (de)regulation in biomedicine.