bluuebunny/crossref_metadata_2025 huggingface dataset:
Re‐Determination of the Crystal Structure of MIL‐91(Al)
Authors: Hermer Nele , Wharmby Michael T. , Stock Norbert
Published: December 2016

The structure of one of the first permanently porous metal phosphonates, MIL‐91(Al) was re‐determined using high resolution synchrotron powder X‐ray diffraction data. The new model is in a lower symmetry space group, with no disordered ligands in the structure, whilst remaining otherwise consistent with the reported compound. New milder synthetic conditions were also developed.
Hooper, Long, Nishimura, Sluijs, and Villarini  Receive 2016 James B. Macelwane Medals
Authors:   AGU
Published: December 2016

Andy Hooper, Maureen D. Long, Toshi Nishimura, Appy Sluijs, and Gabriele Villarini were awarded the 2016 James B. Macelwane Medal at the American Geophysical Union Fall Meeting Honors Ceremony, held on 14 December 2016 in San Francisco, Calif. The medal is for "significant contributions to the geophysical sciences by an outstanding ­­early-​­career scientist."
Using Isotope Fingerprints to Solve a Methane Mystery
Authors: Wheeling Kate
Published: December 2016

Atmospheric methane levels are rising, and isotopic ratios within the greenhouse gas suggest that the tropics may be to blame.
Microbiota network and mathematic microbe mutualism in colostrum and mature milk collected in two different geographic areas: Italy versus Burundi
Authors: Drago Lorenzo , Toscano Marco , De Grandi Roberta , Grossi Enzo , Padovani Ezio M , Peroni Diego G
Published: December 2016

Human milk is essential for the initial development of newborns, as it provides all nutrients and vitamins, such as vitamin D, and represents a great source of commensal bacteria. Here we explore the microbiota network of colostrum and mature milk of Italian and Burundian mothers using the auto contractive map (AutoCM), a new methodology based on artificial neural network (ANN) architecture. We were able to demonstrate the microbiota of human milk to be a dynamic, and complex, ecosystem with different bacterial networks among different populations containing diverse microbial hubs and central nodes, which change during the transition from colostrum to mature milk. Furthermore, a greater abundance of anaerobic intestinal bacteria in mature milk compared with colostrum samples has been observed. The association of complex mathematic systems such as ANN and AutoCM adopted to metagenomics analysis represents an innovative approach to investigate in detail specific bacterial interactions in biological samples.
Monocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation
Authors: Singh Tej Pratap , Zhang Howard H. , Borek Izabela , Wolf Peter , Hedrick Michael N. , Singh Satya P. , Kelsall Brian L. , Clausen Bjorn E. , Farber Joshua M.
Published: December 2016

Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. Here we show that DCs are required for psoriasis-like changes in mouse skin induced by the local injection of IL-23. However, Flt3L-dependent DCs and resident Langerhans cells are dispensable for the inflammation. In epidermis and dermis, the critical DCs are TNF-producing and IL-1β-producing monocyte-derived DCs, including a population of inflammatory Langerhans cells. Depleting Ly6Chi blood monocytes reduces DC accumulation and the skin changes induced either by injecting IL-23 or by application of the TLR7 agonist imiquimod. Moreover, we find that IL-23-induced inflammation requires expression of CCR6 by DCs or their precursors, and that CCR6 mediates monocyte trafficking into inflamed skin. Collectively, our results imply that monocyte-derived cells are critical contributors to psoriasis through production of inflammatory cytokines that augment the activation of skin T cells.
Imaging electric field dynamics with graphene optoelectronics
Authors: Horng Jason , Balch Halleh B. , McGuire Allister F. , Tsai Hsin-Zon , Forrester Patrick R. , Crommie Michael F. , Cui Bianxiao , Wang Feng
Published: December 2016

The use of electric fields for signalling and control in liquids is widespread, spanning bioelectric activity in cells to electrical manipulation of microstructures in lab-on-a-chip devices. However, an appropriate tool to resolve the spatio-temporal distribution of electric fields over a large dynamic range has yet to be developed. Here we present a label-free method to image local electric fields in real time and under ambient conditions. Our technique combines the unique gate-variable optical transitions of graphene with a critically coupled planar waveguide platform that enables highly sensitive detection of local electric fields with a voltage sensitivity of a few microvolts, a spatial resolution of tens of micrometres and a frequency response over tens of kilohertz. Our imaging platform enables parallel detection of electric fields over a large field of view and can be tailored to broad applications spanning lab-on-a-chip device engineering to analysis of bioelectric phenomena.
Tuning magnetic spirals beyond room temperature with chemical disorder
Authors: Morin Mickaël , Canévet Emmanuel , Raynaud Adrien , Bartkowiak Marek , Sheptyakov Denis , Ban Voraksmy , Kenzelmann Michel , Pomjakushina Ekaterina , Conder Kazimierz , Medarde Marisa
Published: December 2016

In the past years, magnetism-driven ferroelectricity and gigantic magnetoelectric effects have been reported for a number of frustrated magnets featuring ordered spiral magnetic phases. Such materials are of high-current interest due to their potential for spintronics and low-power magnetoelectric devices. However, their low-magnetic ordering temperatures (typically <100 K) greatly restrict their fields of application. Here we demonstrate that the onset temperature of the spiral phase in the perovskite YBaCuFeO5 can be increased by more than 150 K through a controlled manipulation of the Fe/Cu chemical disorder. Moreover, we show that this novel mechanism can stabilize the magnetic spiral state of YBaCuFeO5 above the symbolic value of 25 °C at zero magnetic field. Our findings demonstrate that the properties of magnetic spirals, including its wavelength and stability range, can be engineered through the control of chemical disorder, offering a great potential for the design of materials with magnetoelectric properties beyond room temperature.
Transport of lipophilic carboxylates is mediated by transmembrane helix 2 in multidrug transporter AcrB
Authors: Oswald Christine , Tam Heng-Keat , Pos Klaas M.
Published: December 2016

The deployment of multidrug efflux pumps is a powerful defence mechanism for Gram-negative bacterial cells when exposed to antimicrobial agents. The major multidrug efflux transport system in Escherichia coli, AcrAB–TolC, is a tripartite system using the proton-motive force as an energy source. The polyspecific substrate-binding module AcrB uses various pathways to sequester drugs from the periplasm and outer leaflet of the inner membrane. Here we report the asymmetric AcrB structure in complex with fusidic acid at a resolution of 2.5 Å and mutational analysis of the putative fusidic acid binding site at the transmembrane domain. A groove shaped by the interface between transmembrane helix 1 (TM1) and TM2 specifically binds fusidic acid and other lipophilic carboxylated drugs. We propose that these bound drugs are actively displaced by an upward movement of TM2 towards the AcrB periplasmic porter domain in response to protonation events in the transmembrane domain.
Interplay of Dirac electrons and magnetism in CaMnBi2 and SrMnBi2
Authors: Zhang Anmin , Liu Changle , Yi Changjiang , Zhao Guihua , Xia Tian-long , Ji Jianting , Shi Youguo , Yu Rong , Wang Xiaoqun , Chen Changfeng , Zhang Qingming
Published: December 2016

Dirac materials exhibit intriguing low-energy carrier dynamics that offer a fertile ground for novel physics discovery. Of particular interest is the interplay of Dirac carriers with other quantum phenomena such as magnetism. Here we report on a two-magnon Raman scattering study of AMnBi2 (A=Ca, Sr), a prototypical magnetic Dirac system comprising alternating Dirac carrier and magnetic layers. We present the first accurate determination of the exchange energies in these compounds and, by comparison with the reference compound BaMn2Bi2, we show that the Dirac carrier layers in AMnBi2 significantly enhance the exchange coupling between the magnetic layers, which in turn drives a charge-gap opening along the Dirac locus. Our findings break new grounds in unveiling the fundamental physics of magnetic Dirac materials, which offer a novel platform for probing a distinct type of spin–Fermion interaction. The results also hold great promise for applications in magnetic Dirac devices.
Engineering orthogonal dual transcription factors for multi-input synthetic promoters
Authors: Brödel Andreas K. , Jaramillo Alfonso , Isalan Mark
Published: December 2016

Synthetic biology has seen an explosive growth in the capability of engineering artificial gene circuits from transcription factors (TFs), particularly in bacteria. However, most artificial networks still employ the same core set of TFs (for example LacI, TetR and cI). The TFs mostly function via repression and it is difficult to integrate multiple inputs in promoter logic. Here we present to our knowledge the first set of dual activator-repressor switches for orthogonal logic gates, based on bacteriophage λ cI variants and multi-input promoter architectures. Our toolkit contains 12 TFs, flexibly operating as activators, repressors, dual activator–repressors or dual repressor–repressors, on up to 270 synthetic promoters. To engineer non cross-reacting cI variants, we design a new M13 phagemid-based system for the directed evolution of biomolecules. Because cI is used in so many synthetic biology projects, the new set of variants will easily slot into the existing projects of other groups, greatly expanding current engineering capacities.
Serotonergic dysfunctions and abnormal iron metabolism: Relevant to mental fatigue of Parkinson disease
Authors: Zuo Li-Jun , Yu Shu-Yang , Hu Yang , Wang Fang , Piao Ying-Shan , Lian Teng-Hong , Yu Qiu-Jin , Wang Rui-Dan , Li Li-Xia , Guo Peng , Du Yang , Zhu Rong-Yan , Jin Zhao , Wang Ya-Jie , Wang Xiao-Min , Chan Piu , Chen Sheng-Di , Wang Yong-Jun , Zhang Wei
Published: December 2016

Fatigue is a very common non-motor symptom in Parkinson disease (PD) patients. It included physical fatigue and mental fatigue. The potential mechanisms of mental fatigue involving serotonergic dysfunction and abnormal iron metabolism are still unknown. Therefore, we evaluated the fatigue symptoms, classified PD patients into fatigue group and non-fatigue group, and detected the levels of serotonin, iron and related proteins in CSF and serum. In CSF, 5-HT level is significantly decreased and the levels of iron and transferrin are dramatically increased in fatigue group. In fatigue group, mental fatigue score is negatively correlated with 5-HT level in CSF, and positively correlated with the scores of depression and excessive daytime sleepiness, and disease duration, also, mental fatigue is positively correlated with the levels of iron and transferrin in CSF. Transferrin level is negatively correlated with 5-HT level in CSF. In serum, the levels of 5-HT and transferrin are markedly decreased in fatigue group; mental fatigue score exhibits a negative correlation with 5-HT level. Thus serotonin dysfunction in both central and peripheral systems may be correlated with mental fatigue through abnormal iron metabolism. Depression, excessive daytime sleepiness and disease duration were the risk factors for mental fatigue of PD.
A self-consistent spin-diffusion model for micromagnetics
Authors: Abert Claas , Ruggeri Michele , Bruckner Florian , Vogler Christoph , Manchon Aurelien , Praetorius Dirk , Suess Dieter
Published: December 2016

We propose a three-dimensional micromagnetic model that dynamically solves the Landau-Lifshitz-Gilbert equation coupled to the full spin-diffusion equation. In contrast to previous methods, we solve for the magnetization dynamics and the electric potential in a self-consistent fashion. This treatment allows for an accurate description of magnetization dependent resistance changes. Moreover, the presented algorithm describes both spin accumulation due to smooth magnetization transitions and due to material interfaces as in multilayer structures. The model and its finite-element implementation are validated by current driven motion of a magnetic vortex structure. In a second experiment, the resistivity of a magnetic multilayer structure in dependence of the tilting angle of the magnetization in the different layers is investigated. Both examples show good agreement with reference simulations and experiments respectively.
The complete 12 Mb genome and transcriptome of Nonomuraea gerenzanensis with new insights into its duplicated “magic” RNA polymerase
Authors: D’Argenio Valeria , Petrillo Mauro , Pasanisi Daniela , Pagliarulo Caterina , Colicchio Roberta , Talà Adelfia , de Biase Maria Stella , Zanfardino Mario , Scolamiero Emanuela , Pagliuca Chiara , Gaballo Antonio , Cicatiello Annunziata Gaetana , Cantiello Piergiuseppe , Postiglione Irene , Naso Barbara , Boccia Angelo , Durante Miriana , Cozzuto Luca , Salvatore Paola , Paolella Giovanni , Salvatore Francesco , Alifano Pietro
Published: December 2016

In contrast to the widely accepted consensus of the existence of a single RNA polymerase in bacteria, several actinomycetes have been recently shown to possess two forms of RNA polymerases due the to co-existence of two rpoB paralogs in their genome. However, the biological significance of the rpoB duplication is obscure. In this study we have determined the genome sequence of the lipoglycopeptide antibiotic A40926 producer Nonomuraea gerenzanensis ATCC 39727, an actinomycete with a large genome and two rpoB genes, i.e. rpoB(S) (the wild-type gene) and rpoB(R) (the mutant-type gene). We next analyzed the transcriptional and metabolite profiles in the wild-type gene and in two derivative strains over-expressing either rpoB(R) or a mutated form of this gene to explore the physiological role and biotechnological potential of the “mutant-type” RNA polymerase. We show that rpoB(R) controls antibiotic production and a wide range of metabolic adaptive behaviors in response to environmental pH. This may give interesting perspectives also with regard to biotechnological applications.
Lyn prevents aberrant inflammatory responses to Pseudomonas infection in mammalian systems by repressing a SHIP-1-associated signaling cluster
Authors: Li Rongpeng , Fang Lizhu , Pu Qinqin , Lin Ping , Hoggarth Austin , Huang Huang , Li Xuefeng , Li Guoping , Wu Min
Published: December 2016

The pleiotropic Src kinase Lyn has critical roles in host defense in alveolar macrophages against bacterial infection, but the underlying mechanism for Lyn-mediated inflammatory response remains largely elusive. Using mouse Pseudomonas aeruginosa infection models, we observed that Lyn−/− mice manifest severe lung injury and enhanced inflammatory responses, compared with wild-type littermates. We demonstrate that Lyn exerts this immune function through interaction with IL-6 receptor and cytoskeletal protein Ezrin via its SH2 and SH3 domains. Depletion of Lyn results in excessive STAT3 activation, and enhanced the Src homology 2-containing inositol-5-phopsphatase 1 (SHIP-1) expression. Deletion of SHIP-1 in Lyn−/− mice (double knockout) promotes mouse survival and reduces inflammatory responses during P. aeruginosa infection, revealing the rescue of the deadly infectious phenotype in Lyn deficiency. Mechanistically, loss of SHIP-1 reduces NF-κB-dependent cytokine production and dampens MAP kinase activation through a TLR4-independent PI3K/Akt pathway. These findings reveal Lyn as a regulator for host immune response against P. aeruginosa infection through SHIP-1 and IL-6/STAT3 signaling pathway in alveolar macrophages.
A preclinical evaluation of an autologous living hyaline-like cartilaginous graft for articular cartilage repair: a pilot study
Authors: Peck Yvonne , He Pengfei , Chilla Geetha Soujanya V. N. , Poh Chueh Loo , Wang Dong-An
Published: December 2016

In this pilot study, an autologous synthetic scaffold-free construct with hyaline quality, termed living hyaline cartilaginous graft (LhCG), was applied for treating cartilage lesions. Implantation of autologous LhCG was done at load-bearing regions of the knees in skeletally mature mini-pigs for 6 months. Over the course of this study, significant radiographical improvement in LhCG treated sites was observed via magnetic resonance imaging. Furthermore, macroscopic repair was effected by LhCG at endpoint. Microscopic inspection revealed that LhCG engraftment restored cartilage thickness, promoted integration with surrounding native cartilage, produced abundant cartilage-specific matrix molecules and re-established an intact superficial tangential zone. Importantly, the repair efficacy of LhCG was quantitatively shown to be comparable to native, unaffected cartilage in terms of biochemical composition and biomechanical properties. There were no complications related to the donor site of cartilage biopsy. Collectively, these results imply that LhCG engraftment may be a viable approach for articular cartilage repair.
Proteomic analysis of scallop hepatopancreatic extract provides insights into marine polysaccharide digestion
Authors: Lyu Qianqian , Jiao Wenqian , Zhang Keke , Bao Zhenmin , Wang Shi , Liu Weizhi
Published: December 2016

Marine polysaccharides are used in a variety of applications, and the enzymes that degrade these polysaccharides are of increasing interest. The main food source of herbivorous marine mollusks is seaweed, and several polysaccharide-degrading enzymes have been extracted from mollusk digestive glands (hepatopancreases). Here, we used a comprehensive proteomic approach to examine the hepatopancreatic proteins of the Zhikong scallop (Chlamys farreri). We identified 435 proteins, the majority of which were lysosomal enzymes and carbohydrate and protein metabolism enzymes. However, several new enzymes related to polysaccharide metabolism were also identified. Phylogenetic and structural analyses of these enzymes suggest that these polysaccharide-degrading enzymes may have a variety of potential substrate specificities. Taken together, our study characterizes several novel polysaccharide-degrading enzymes in the scallop hepatopancreas and provides an enhanced view of these enzymes and a greater understanding of marine polysaccharide digestion.
A Jurassic wood providing insights into the earliest step in Ginkgo wood evolution
Authors: Jiang Zikun , Wang Yongdong , Philippe Marc , Zhang Wu , Tian Ning , Zheng Shaolin
Published: December 2016

The fossil record ofGinkgoleaf and reproductive organs has been well dated to the Mid-Jurassic (170 Myr). However, the fossil wood record that can safely be assigned to Ginkgoales has not yet been reported from strata predating the late Early Cretaceous (ca. 100 Myr). Here, we report a new fossil wood from the Mid-Late Jurassic transition deposit (153–165 Myr) of northeastern China. The new fossil wood specimen displays severalGinkgofeatures, including inflated axial parenchyma and intrusive tracheid tips. Because it is only slightly younger than the oldest recordedGinkgoreproductive organs (the Yima Formation, 170 Myr), this fossil wood very probably represents the oldest bona fide fossilGinkgowood and the missing ancestral form ofGinkgowood evolution.
Analysis of High-altitude Syndrome and the Underlying Gene Polymorphisms Associated with Acute Mountain Sickness after a Rapid Ascent to High-altitude
Authors: Yu Jie , Zeng Ying , Chen Guozhu , Bian Shizhu , Qiu Youzhu , Liu Xi , Xu Baida , Song Pan , Zhang Jihang , Qin Jun , Huang Lan
Published: December 2016

To investigated the objective indicators and potential genotypes for acute mountain sickness (AMS). 176 male subjects were evaluated for symptoms scores and physiological parameters at 3700 m. EPAS1 gene polymorphisms were explored and verified effects of potential genotypes on pulmonary function by inhaled budesonide. The incidence of AMS was 53.98% (95/176). The individuals who suffered from headache with anxiety and greater changes in heart rate (HR), the forced vital capacity (FVC), and mean flow velocity of basilar artery (Vm-BA), all of which were likely to develop AMS. The rs4953348 polymorphism of EPAS1 gene had a significant correlation with the SaO2 level and AMS, and a significant difference in the AG and GG genotype distribution between the AMS and non-AMS groups. The spirometric parameters were significantly lower, but HR (P = 0.036) and Vm-BA (P = 0.042) significantly higher in the AMS subjects
with the G allele than those with the A allele. In summary, changes in HR (≥82 beats/min), FVC (≤4.2 Lt) and Vm-BA (≥43 cm/s) levels may serve as predictors for diagnosing AMS accompanied by high-altitude syndrome. The A allele of rs4953348 is a protective factor for AMS through HR and Vm-BA compensation, while the G allele may contribute to hypoxic pulmonary hypertension in AMS.
Generation of kidney tubular organoids from human pluripotent stem cells
Authors: Yamaguchi Shintaro , Morizane Ryuji , Homma Koichiro , Monkawa Toshiaki , Suzuki Sayuri , Fujii Shizuka , Koda Muneaki , Hiratsuka Ken , Yamashita Maho , Yoshida Tadashi , Wakino Shu , Hayashi Koichi , Sasaki Junichi , Hori Shingo , Itoh Hiroshi
Published: December 2016

Recent advances in stem cell research have resulted in methods to generate kidney organoids from human pluripotent stem cells (hPSCs), which contain cells of multiple lineages including nephron epithelial cells. Methods to purify specific types of cells from differentiated hPSCs, however, have not been established well. For bioengineering, cell transplantation, and disease modeling, it would be useful to establish those methods to obtain pure populations of specific types of kidney cells. Here, we report a simple two-step differentiation protocol to generate kidney tubular organoids from hPSCs with direct purification of KSP (kidney specific protein)-positive cells using anti-KSP antibody. We first differentiated hPSCs into mesoderm cells using a glycogen synthase kinase-3β inhibitor for 3 days, then cultured cells in renal epithelial growth medium to induce KSP+ cells. We purified KSP+ cells using flow cytometry with anti-KSP antibody, which exhibited characteristics of all segments of kidney tubular cells and cultured KSP+ cells in 3D Matrigel, which formed tubular organoids in vitro. The formation of tubular organoids by KSP+ cells induced the acquisition of functional kidney tubules. KSP+ cells also allowed for the generation of chimeric kidney cultures in which human cells self-assembled into 3D tubular structures in combination with mouse embryonic kidney cells.
Immune Responses Induced by Recombinant Bacillus Subtilis Expressing the Hemagglutinin Protein of H5N1 in chickens
Authors: Mou Chunxiao , Zhu Liqi , Yang Jingjing , Xu Wenwen , Cheng Xiaoying , Yang Qian
Published: December 2016

To develop an effective, safe, and convenient vaccine for the prevention of highly pathogenic avian influenza (HPAI) H5N1, we have constructed a recombinant Bacillus subtilis strain (B.S.-HA) expressing the hemagglutinin (HA) protein. Then we evaluated the immune function in chicken bone marrow derived dendritic cells (BM-DCs), and the immune response after oral immunization. Our results show that the recombinant Bacillus subtilis B.S.-HA could be sampled by BM-DCs in vitro and increase the BM-DCs major histocompatibility complex (MHC) II phenotype. The weight, height of the small intestine villus, and lymphoid tissue area of the ileum increased significantly in B.S.-HA immunized chickens (P < 0.05 or P < 0.01). B.S.-HA induced the secretion of cytokines and the expression of Toll-like receptors in the trachea and small intestine (P < 0.05 or P < 0.01). In addition, B.S.-HA elevated the specific IgA titers in the trachea, IgG and HI antibody titers in serum (P < 0.05 or P < 0.01). Therefore, B.S.-HA provides a potential novel strategy and approach for developing an H5N1 vaccine.
Nrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis
Authors: Zhou Wencheng , Mo Xiaoting , Cui Wenhui , Zhang Zhihui , Li Delin , Li Liucheng , Xu Liang , Yao Hongwei , Gao Jian
Published: December 2016

Epithelial-mesenchymal transition (EMT) is a phenotype conversion that plays a critical role in the development of pulmonary fibrosis (PF). It is known that snail could regulate the progression of EMT. Nuclear factor erythroid 2 related factor 2 (Nrf2), a key regulator of antioxidant defense system, protects cells against oxidative stress. However, it is not known whether Nrf2 regulates snail thereby modulating the development of PF. Here, bleomycin (BLM) was intratracheally injected into both Nrf2-knockout (Nrf2−/−) and wild-type mice to compare the development of PF. Rat type II alveolar epithelial cells (RLE-6TN) were treated with a specific Nrf2 activator sulforaphane, or transfected with Nrf2 and snail siRNAs to determine their effects on transforming growth factor β1 (TGF-β1)-induced EMT. We found that BLM-induced EMT and lung fibrosis were more severe in Nrf2−/− mice compared to wild-type mice. In vitro, sulforaphane treatment attenuated TGF-β1-induced EMT, accompanied by the down-regulation of snail. Inversely, silencing Nrf2 by siRNA enhanced TGF-β1-induced EMT along with increased expression of snail. Interestingly, when snail was silenced by siRNA, sulforaphane treatment was unable to reduce the progression of EMT in RLE-6TN cells. These findings suggest that Nrf2 attenuates EMT and fibrosis process by regulating the expression of snail in PF.
Microstructure Imaging of Crossing (MIX) White Matter Fibers from diffusion MRI
Authors: Farooq Hamza , Xu Junqian , Nam Jung Who , Keefe Daniel F. , Yacoub Essa , Georgiou Tryphon , Lenglet Christophe
Published: December 2016

Diffusion MRI (dMRI) reveals microstructural features of the brain white matter by quantifying the anisotropic diffusion of water molecules within axonal bundles. Yet, identifying features such as axonal orientation dispersion, density, diameter, etc., in complex white matter fiber configurations (e.g. crossings) has proved challenging. Besides optimized data acquisition and advanced biophysical models, computational procedures to fit such models to the data are critical. However, these procedures have been largely overlooked by the dMRI microstructure community and new, more versatile, approaches are needed to solve complex biophysical model fitting problems. Existing methods are limited to models assuming single fiber orientation, relevant to limited brain areas like the corpus callosum, or multiple orientations but without the ability to extract detailed microstructural features. Here, we introduce a new and versatile optimization technique (MIX), which enables microstructure imaging of crossing white matter fibers. We provide a MATLAB implementation of MIX, and demonstrate its applicability to general microstructure models in fiber crossings using synthetic as well as ex-vivo and in-vivo brain data.
A CRISPR/Cas9 Functional Screen Identifies Rare Tumor Suppressors
Authors: Katigbak Alexandra , Cencic Regina , Robert Francis , Sénécha Patrick , Scuoppo Claudio , Pelletier Jerry
Published: December 2016

An enormous amount of tumor sequencing data has been generated through large scale sequencing efforts. The functional consequences of the majority of mutations identified by such projects remain an open, unexplored question. This problem is particularly complicated in the case of rare mutations where frequency of occurrence alone or prediction of functional consequences are insufficient to distinguish driver from passenger or bystander mutations. We combine genome editing technology with a powerful mouse cancer model to uncover previously unsuspected rare oncogenic mutations in Burkitt’s lymphoma. We identify two candidate tumor suppressors whose loss cooperate with MYC over-expression to accelerate lymphomagenesis. Our results highlight the utility of in vivo CRISPR/Cas9 screens combined with powerful mouse models to identify and validate rare oncogenic modifier events from tumor mutational data.
The influence of ionic strength on carbonate-based spectroscopic barometry for aqueous fluids: an in-situ Raman study on Na2CO3-NaCl solutions
Authors: Wu Jia , Wang Shixia , Zheng Haifei
Published: December 2016

The Raman wavenumber of the symmetric stretching vibration of carbonate ion (ν1-CO32−) was measured in three aqueous solutions containing 2.0 mol·L−1 Na2CO3 and 0.20, 0.42, or 0.92 mol·L−1 NaCl, respectively, from 122 to 1538 MPa at 22 °C using a moissanite anvil cell. The ν1 Raman signal linearly shifted to higher wavenumbers with increasing pressure. Most importantly, the slope of ν1-CO32− Raman frequency shift (∂ν1/∂P)I was independent of NaCl concentration. Moreover, elevated ionic strength was found to shift the apparent outline of the carbonate peak toward low wavenumbers, possibly by increasing the proportion of the contact ion pair NaCO3−. Further investigations revealed no cross-interaction between the pressure effect and the ionic strength effect on the Raman spectra, possibly because the distribution of different ion-pair species in the carbonate equilibrium was largely pressure-independent. These results suggested that the ionic strength should be incorporated as an additional constraint for measuring the internal pressure of various solution-based systems. Combining the ν1-CO32− Raman frequency slope with the pressure herein with the values for the temperature or the ionic strength dependencies determined from previous studies, we developed an empirical equation that can be used to estimate the pressure of carbonate-bearing aqueous solutions.
Galectin-3 Induces a Pro-degradative/inflammatory Gene Signature in Human Chondrocytes, Teaming Up with Galectin-1 in Osteoarthritis Pathogenesis
Authors: Weinmann Daniela , Schlangen Karin , André Sabine , Schmidt Sebastian , Walzer Sonja M. , Kubista Bernd , Windhager Reinhard , Toegel Stefan , Gabius Hans-Joachim
Published: December 2016

Inflammatory chemo- and cytokines and matrix-degrading proteases underlie the progression of osteoarthritis (OA). Aiming to define upstream regulators for these disease markers, we pursued initial evidence for an upregulation of members of the adhesion/growth-regulatory galectin family. Immunohistochemical localization of galectin-3 (Gal-3) in sections of human cartilage with increasing levels of degeneration revealed a linear correlation reaching a chondrocyte positivity of 60%. Presence in situ was cytoplasmic, the lectin was secreted from OA chondrocytes in culture and binding of Gal-3 yielded lactose-inhibitable surface staining. Exposure of cells to the lectin led to enhanced gene expression and secretion of functional disease markers. Genome-wide transcriptomic analysis broadened this result to reveal a pro-degradative/inflammatory gene signature under the control of NF-κB. Fittingly, targeting this route of activation by inhibitors impaired the unfavourable response to Gal-3 binding, as also seen by shortening the lectin’s collagen-like repeat region. Gal-3’s activation profile overlaps with that of homodimeric galectin-1 (Gal-1) and also has distinctive (supplementing) features. Tested at subsaturating concentrations in a mixture, we found cooperation between the two galectins, apparently able to team up to promote OA pathogenesis. In summary, our results suggest that a network of endogenous lectins is relevant for initiating this process cascade.
Vibrational density of states and thermodynamics at the nanoscale: the 3D-2D transition in gold nanostructures
Authors: Carles R. , Benzo P. , Pécassou B. , Bonafos C.
Published: December 2016

Surface enhanced Raman scattering (SERS) is generally and widely used to enhance the vibrational fingerprint of molecules located at the vicinity of noble metal nanoparticles. In this work, SERS is originally used to enhance the own vibrational density of states (VDOS) of nude and isolated gold nanoparticles. This offers the opportunity of analyzing finite size effects on the lattice dynamics which remains unattainable with conventional techniques based on neutron or x-ray inelastic scattering. By reducing the size down to few nanometers, the role of surface atoms versus volume atoms become dominant, and the “text-book” 3D-2D transition on the dynamical behavior is experimentally emphasized. “Anomalies” that have been predicted by a large panel of simulations at the atomic scale, are really observed, like the enhancement of the VDOS at low frequencies or the occurrence of localized modes at frequencies beyond the cut-off in bulk. Consequences on the thermodynamic properties at the nanoscale, like the reduction of the Debye temperature or the excess of the specific heat, have been evaluated. Finally the high sensitivity of reminiscent bulk-like phonons on the arrangements at the atomic scale is used to access the morphology and internal disorder of the nanoparticles.
Dual-seq transcriptomics reveals the battle for iron during Pseudomonas aeruginosa acute murine pneumonia
Authors: Damron F. Heath , Oglesby-Sherrouse Amanda G. , Wilks Angela , Barbier Mariette
Published: December 2016

Determining bacterial gene expression during infection is fundamental to understand pathogenesis. In this study, we used dual RNA-seq to simultaneously measure P. aeruginosa and the murine host’s gene expression and response to respiratory infection. Bacterial genes encoding products involved in metabolism and virulence were differentially expressed during infection and the type III and VI secretion systems were highly expressed in vivo. Strikingly, heme acquisition, ferric-enterobactin transport, and pyoverdine biosynthesis genes were found to be significantly up-regulated during infection. In the mouse, we profiled the acute immune response to P. aeruginosa and identified the pro-inflammatory cytokines involved in acute response to the bacterium in the lung. Additionally, we also identified numerous host iron sequestration systems upregulated during infection. Overall, this work sheds light on how P. aeruginosa triggers a pro-inflammatory response and competes for iron with the host during infection, as iron is one of the central elements for which both pathogen and host fight during acute pneumonia.
Efficient DNA–Polymer Coupling in Organic Solvents: A Survey of Amide Coupling, Thiol-Ene and Tetrazine–Norbornene Chemistries Applied to Conjugation of Poly(N-Isopropylacrylamide)
Authors: Wilks Thomas R. , O’Reilly Rachel K.
Published: December 2016

A range of chemistries were explored for the efficient covalent conjugation of DNA to poly(N-isopropylacrylamide) (poly(NIPAM)) in organic solvents. Amide coupling and thiol–ene Michael addition were found to be ineffective for the synthesis of the desired products. However, the inverse electron-demand Diels–Alder (DAinv) reaction between tetrazine (Tz) and norbornene (Nb) was found to give DNA–polymer conjugates in good yields (up to 40%) in organic solvents (N,N-dimethylformamide, N,N-dimethylacetamide and N-methyl-2-pyrrolidone), and without the need for a catalyst. Methods for the synthesis of Tz-and Nb- functionalised DNA were developed, along with a post-polymerisation functionalisation strategy for the production of Tz-functionalised polymers.
Brown adipogenic potential of brown adipocytes and peri-renal adipocytes from human embryo
Authors: Wu Nan-Nan , Zhang Chuan-Hai , Lee Hyuek-Jong , Ma Yan , Wang Xin , Ma Xiao-Juan , Ma Wei , Zhao Dong , Feng Ying-Mei
Published: December 2016

Both brown adipocytes (BAC) and beige cells hold therapeutic potential for the treatment of metabolic disorders. Unfortunately, the amount and activity of these cells are limited in adults. Although BAC marker expression has been shown in peri-renal adipose tissues in children and adults, functional assessment is lacking. Furthermore, it is entirely unknown whether adipose progenitors are present in human embryo and able to give rise to BAC in situ during evolution. Therefore, adipose tissues in the interscapular and peri-renal regions were dissected from human embryo and subcutaneous white adipose tissues (sWAT) were obtained from an adult. After subjected to differentiation in vitro, adipocyte progenitors were detected present in all these adipose tissues. When stimulated for adipogenesis, differentiated adipocytes in the intercapular and peri-renal regions showed similar features: (1) induced BAC and beige cell marker expression including UCP1 and PRDM16 and comparable mitochondrion copy number; (2) similar gene expression patterns by RNA-Seq analysis; and (3) similar maximal oxygen consumption rates examined by respirometry. Nevertheless, stimulation of adipocyte progenitors in sWAT induces neither BAC and beige cell marker expression nor any change of oxygen consumption. In conclusion, peri-renal adipocyte progenitors in human embryo hold browning potential for BAC production.
Production of fluorescent dissolved organic matter in Arctic Ocean sediments
Authors: Chen Meilian , Kim Ji-Hoon , Nam Seung-Il , Niessen Frank , Hong Wei-Li , Kang Moo-Hee , Hur Jin
Published: December 2016

Little is known about the production of fluorescent dissolved organic matter (FDOM) in the anoxic oceanic sediments. In this study, sediment pore waters were sampled from four different sites in the Chukchi-East Siberian Seas area to examine the bulk dissolved organic carbon (DOC) and their optical properties. The production of FDOM, coupled with the increase of nutrients, was observed above the sulfate-methane-transition-zone (SMTZ). The presence of FDOM was concurrent with sulfate reduction and increased alkalinity (R2 > 0.96, p < 0.0001), suggesting a link to organic matter degradation. This inference was supported by the positive correlation (R2 > 0.95, p < 0.0001) between the net production of FDOM and the modeled degradation rates of particulate organic carbon sulfate reduction. The production of FDOM was more pronounced in a shallow shelf site S1 with a total net production ranging from 17.9 to 62.3 RU for different FDOM components above the SMTZ depth of ca. 4.1 mbsf, which presumably underwent more accumulation of particulate organic matter than the other three deeper sites. The sediments were generally found to be the sources of CDOM and FDOM to the overlying water column, unearthing a channel of generally bio-refractory and pre-aged DOM to the oceans.
Thiol-Capped Gold Nanoparticles Swell-Encapsulated into Polyurethane as Powerful Antibacterial Surfaces Under Dark and Light Conditions
Authors: Macdonald Thomas J. , Wu Ke , Sehmi Sandeep K. , Noimark Sacha , Peveler William J. , du Toit Hendrik , Voelcker Nicolas H. , Allan Elaine , MacRobert Alexander J. , Gavriilidis Asterios , Parkin Ivan P.
Published: December 2016

A simple procedure to develop antibacterial surfaces using thiol-capped gold nanoparticles (AuNPs) is shown, which effectively kill bacteria under dark and light conditions. The effect of AuNP size and concentration on photo-activated antibacterial surfaces is reported and we show significant size effects, as well as bactericidal activity with crystal violet (CV) coated polyurethane. These materials have been proven to be powerful antibacterial surfaces against both Gram-positive and Gram-negative bacteria. AuNPs of 2, 3 or 5 nm diameter were swell-encapsulated into PU before a coating of CV was applied (known as PU-AuNPs-CV). The antibacterial activity of PU-AuNPs-CV samples was tested against Staphylococcus aureus and Escherichia coli as representative Gram-positive and Gram-negative bacteria under dark and light conditions. All light conditions in this study simulated a typical white-light hospital environment. This work demonstrates that the antibacterial activity of PU-AuNPs-CV samples and the synergistic enhancement of photoactivity of triarylmethane type dyes is highly dependent on nanoparticle size and concentration. The most powerful PU-AuNPs-CV antibacterial surfaces were achieved using 1.0 mg mL−1 swell encapsulation concentrations of 2 nm AuNPs. After two hours, Gram-positive and Gram-negative bacteria were reduced to below the detection limit (>4 log) under dark and light conditions.
Ionizing radiation from Chernobyl affects development of wild carrot plants
Authors: Boratyński Zbyszek , Arias Javi Miranda , Garcia Cristina , Mappes Tapio , Mousseau Timothy A. , Møller Anders P. , Pajares Antonio Jesús Muñoz , Piwczyński Marcin , Tukalenko Eugene
Published: December 2016

Radioactivity released from disasters like Chernobyl and Fukushima is a global hazard and a threat to exposed biota. To minimize the deleterious effects of stressors organisms adopt various strategies. Plants, for example, may delay germination or stay dormant during stressful periods. However, an intense stress may halt germination or heavily affect various developmental stages and select for life history changes. Here, we test for the consequence of exposure to ionizing radiation on plant development. We conducted a common garden experiment in an uncontaminated greenhouse using 660 seeds originating from 33 wild carrots (Daucus carota) collected near the Chernobyl nuclear power plant. These maternal plants had been exposed to radiation levels that varied by three orders of magnitude. We found strong negative effects of elevated radiation on the timing and rates of seed germination. In addition, later stages of development and the timing of emergence of consecutive leaves were delayed by exposure to radiation. We hypothesize that low quality of resources stored in seeds, damaged DNA, or both, delayed development and halted germination of seeds from plants exposed to elevated levels of ionizing radiation. We propose that high levels of spatial heterogeneity in background radiation may hamper adaptive life history responses.
Unraveling gene expression profiles in peripheral motor nerve from amyotrophic lateral sclerosis patients: insights into pathogenesis
Authors: Riva Nilo , Clarelli Ferdinando , Domi Teuta , Cerri Federica , Gallia Francesca , Trimarco Amelia , Brambilla Paola , Lunetta Christian , Lazzerini Alberto , Lauria Giuseppe , Taveggia Carla , Iannaccone Sandro , Nobile-Orazio Eduardo , Comi Giancarlo , D’Antonio Maurizio , Martinelli-Boneschi Filippo , Quattrini Angelo
Published: December 2016

The aim of the present study is to investigate the molecular pathways underlying amyotrophic lateral sclerosis (ALS) pathogenesis within the peripheral nervous system. We analyzed gene expression changes in human motor nerve diagnostic biopsies obtained from eight ALS patients and seven patients affected by motor neuropathy as controls. An integrated transcriptomics and system biology approach was employed. We identified alterations in the expression of 815 genes, with 529 up-regulated and 286 down-regulated in ALS patients. Up-regulated genes clustered around biological process involving RNA processing and protein metabolisms. We observed a significant enrichment of up-regulated small nucleolar RNA transcripts (p = 2.68*10-11) and genes related to endoplasmic reticulum unfolded protein response and chaperone activity. We found a significant down-regulation in ALS of genes related to the glutamate metabolism. Interestingly, a network analysis highlightedHDAC2,belonging to the histone deacetylase family, as the most interacting node. While so far gene expression studies in human ALS have been performed in postmortem tissues, here specimens were obtained from biopsy at an early phase of the disease, making these results new in the field of ALS research and therefore appealing for gene discovery studies.
A method for high-throughput functional imaging of single cells within heterogeneous cell preparations
Authors: Neal Adam S. , Rountree Austin M. , Radtke Jared R. , Yin Jianzhu , Schwartz Michael W. , Hampe Christiane S. , Posner Jonathan D. , Cirulli Vincenzo , Sweet Ian R.
Published: December 2016

Functional characterization of individual cells within heterogeneous tissue preparations is challenging. Here, we report the development of a versatile imaging method that assesses single cell responses of various endpoints in real time, while identifying the individual cell types. Endpoints that can be measured include (but are not limited to) ionic flux (calcium, sodium, potassium and hydrogen), metabolic responsiveness (NAD(P)H, mitochondrial membrane potential), and signal transduction (H2O2 and cAMP). Subsequent to fluorescent imaging, identification of cell types using immunohistochemistry allows for mapping of cell type to their respective functional real time responses. To validate the utility of this method, NAD(P)H responses to glucose of islet alpha versus beta cells generated from dispersed pancreatic islets, followed by the construction of frequency distributions characterizing the variability in the magnitude of each individual cell responses were compared. As expected, no overlap between the glucose response frequency distributions for beta cells versus alpha cells was observed, thereby establishing both the high degree of fidelity and low rate of both false-negatives and false-positives in this approach. This novel method has the ability not only to resolve single cell level functional differences between cell types, but also to characterize functional heterogeneity within a given cell type.
Usefulness of CHA2DS2-VASc Scoring Systems for Predicting Risk of Perioperative Embolism in Patients of Cardiac Myxomas Underwent Surgical Treatment
Authors: Yin Liang , Wang Jing , Li Wei , Ling Xinyu , Xue Qian , Zhang Yufeng , Wang Zhinong
Published: December 2016

Cardiac myxomas are rare but manifested with risk of embolism and often cause unexpected symptoms or sudden death. We retrospectively collected the medical records of patients diagnosed of cardiac myxomas at the cardiac center of our university. Overall 465 patients were included in this study, patients in the embolism group had significantly higher CHA2DS2-VASc scores (P = 0.005). In embolic group, stroke was recorded in 110 (77.14%) patients, while embolic events in the limbs were observed in 10 (2.15%) and 9(1.93%) developed splenic infarction. Patients in embolism group had older age (P = 0.021) and higher BMI (P  <0.001) than those in non-embolism group. There was no significant difference between two groups in terms of time of mechanical ventilation (P = 0.065), ICU stay (P = 0.053), hospital stay (P = 0.071) and volume of drainage (P = 0.083), blood transfusions (P = 0.060) except that patients with embolic events had significantly higher incidence of postoperative atrial fibrillation (P = 0.032) and lower survival rate (P < 0.001). Furthermore, the CHA2DS2-VASc score was a significant predictor of embolism in patients with cardiac myxomas (P = 0.015; P = 0.003) and the Kaplan-Meier analysis obtained a higher rate of embolism in patients with higher stratification of CHA2DS2-VASc scores (P = 0.002). In conclusion, CHA2DS2-VASc scoring scheme was strongly predictive of stroke and embolic events in patients with cardiac myxomas.