bluuebunny/crossref_metadata_2025 huggingface dataset:
Repression of Human T-lymphotropic virus type 1 Long Terminal Repeat sense transcription by Sp1 recruitment to novel Sp1 binding sites
Authors: Fauquenoy Sylvain , Robette Gwenaëlle , Kula Anna , Vanhulle Caroline , Bouchat Sophie , Delacourt Nadège , Rodari Anthony , Marban Céline , Schwartz Christian , Burny Arsène , Rohr Olivier , Van Driessche Benoit , Van Lint Carine
Published: March 2017

Human T-lymphotropic Virus type 1 (HTLV-1) infection is characterized by viral latency in the majority of infected cells and by the absence of viremia. These features are thought to be due to the repression of viral sense transcriptionin vivo. Here, ourin silicoanalysis of the HTLV-1 Long Terminal Repeat (LTR) promoter nucleotide sequence revealed, in addition to the four Sp1 binding sites previously identified, the presence of two additional potential Sp1 sites within the R region. We demonstrated that the Sp1 and Sp3 transcription factors boundin vitroto these two sites and compared the binding affinity for Sp1 of all six different HTLV-1 Sp1 sites. By chromatin immunoprecipitation experiments, we showed Sp1 recruitmentin vivoto the newly identified Sp1 sites. We demonstrated in the nucleosomal context of an episomal reporter vector that the Sp1 sites interfered with both the sense and antisense LTR promoter activities. Interestingly, the Sp1 sites exhibited together a repressor effect on the LTR sense transcriptional activity but had no effect on the LTR antisense activity. Thus, our results demonstrate the presence of two new functional Sp1 binding sites in the HTLV-1 LTR, which act as negativecis-regulatory elements of sense viral transcription.
High-density genetic map and identification of QTLs for responses to temperature and salinity stresses in the model brown alga Ectocarpus
Authors: Avia Komlan , Coelho Susana M. , Montecinos Gabriel J. , Cormier Alexandre , Lerck Fiona , Mauger Stéphane , Faugeron Sylvain , Valero Myriam , Cock J. Mark , Boudry Pierre
Published: March 2017

Deciphering the genetic architecture of adaptation of brown algae to environmental stresses such as temperature and salinity is of evolutionary as well as of practical interest. The filamentous brown algaEctocarpussp. is a model for the brown algae and its genome has been sequenced. As sessile organisms, brown algae need to be capable of resisting the various abiotic stressors that act in the intertidal zone (e.g. osmotic pressure, temperature, salinity, UV radiation) and previous studies have shown that an important proportion of the expressed genes is regulated in response to hyposaline, hypersaline or oxidative stress conditions. Using the double digest RAD sequencing method, we constructed a dense genetic map with 3,588 SNP markers and identified 39 QTLs for growth-related traits and their plasticity under different temperature and salinity conditions (tolerance to high temperature and low salinity). GO enrichment tests within QTL intervals highlighted membrane transport processes such as ion transporters. Our study represents a significant step towards deciphering the genetic basis of adaptation ofEctocarpussp. to stress conditions and provides a substantial resource to the increasing list of tools generated for the species.
Prolonged high-fat diet induces gradual and fat depot-specific DNA methylation changes in adult mice
Authors: Zwamborn Ramona A. J. , Slieker Roderick C. , Mulder Petra C. A. , Zoetemelk Inge , Verschuren Lars , Suchiman H. Eka D. , Toet Karin H. , Droog Simone , Slagboom P. Eline , Kooistra Teake , Kleemann Robert , Heijmans Bastiaan T.
Published: March 2017

High-fat diets (HFD) are thought to contribute to the development of metabolism-related diseases. The long-term impact of HFD may be mediated by epigenetic mechanisms, and indeed, HFD has been reported to induce DNA methylation changes in white adipose tissue (WAT) near metabolism related genes. However, previous studies were limited to a single WAT depot, a single time-point and primarily examined the pre-pubertal period. To define dynamic DNA methylation patterns specific for WAT depots, we investigated DNA methylation of Pparg2 and Leptin in gonadal adipose tissue (GAT) and subcutaneous adipose tissue (SAT), at baseline and after 6, 12 and 24 weeks of HFD exposure in adult mice. HFD induced hypermethylation of both the Leptin promoter (max. 19.6% at week 24, P = 2.6·10−3) and the Pparg2 promoter in GAT (max. 10.5% at week 12, P = 0.001). The differential methylation was independent of immune cell infiltration upon HFD exposure. In contrast, no differential methylation in the Pparg2 and Leptin promoter was observed in SAT. Leptin and Pparg2 DNA methylation were correlated with gene expression in GAT. Our study shows that prolonged exposure to HFD in adulthood is associated with a gradually increasing DNA methylation level at the Leptin and Pparg2 promoters in a depot-specific manner.
Targeted mutagenesis in the medicinal plant Salvia miltiorrhiza
Authors: Li Bin , Cui Guanghong , Shen Guoan , Zhan Zhilai , Huang Luqi , Chen Jiachun , Qi Xiaoquan
Published: March 2017

CRISPR/Cas9 is a powerful genome editing tool that has been extensively used in model plants and crops, such as Arabidopsis thaliana, rice, wheat, and soybean. Here, we report the use of CRISPR/Cas9 to precisely knock out the committed diterpene synthase gene (SmCPS1) involved in tanshinone biosynthesis in Salvia miltiorrhiza, a traditional Chinese medicinal herb with significant pharmacological activities, such as vasorelaxation, protection against ischemia-reperfusion injury, and antiarrhythmic effects. Three homozygous and eight chimeric mutants were obtained from 26 independent transgenic hairy root lines by Agrobacterium rhizogenes-mediated transformation. The metabolomic analysis based on LC-qTOF-MS and Q-TRAP-LC-MS/MS revealed that tanshinones, especially cryptotanshinone, tanshinone IIA and tanshinone I, are completely missing in homozygous mutants, without influencing other phenolic acid metabolites. By contrast, tanshinones are decreased but still detectable in chimeric mutants, which is similar to a previously-reported an RNAi study of SmCPS1. These results demonstrate that Agrobacterium rhizogenes- mediated transformation using CRISPR/Cas9 is a simple and efficient genome editing tool in S. miltiorrhiza, thus paving the way for large-scale genome editing in S. miltiorrhiza, which is important for pathway elucidation of secondary metabolites, quality improvement, and yield increases for this valuable traditional Chinese medicinal herb.
Genetic variation architecture of mitochondrial genome reveals the differentiation in Korean landrace and weedy rice
Authors: Tong Wei , He Qiang , Park Yong-Jin
Published: March 2017

Mitochondrial genome variations have been detected despite the overall conservation of this gene content, which has been valuable for plant population genetics and evolutionary studies. Here, we describe mitochondrial variation architecture and our performance of a phylogenetic dissection of Korean landrace and weedy rice. A total of 4,717 variations across the mitochondrial genome were identified adjunct with 10 wild rice. Genetic diversity assessment revealed that wild rice has higher nucleotide diversity than landrace and/or weedy, and landrace rice has higher diversity than weedy rice. Genetic distance was suggestive of a high level of breeding between landrace and weedy rice, and the landrace showing a closer association with wild rice than weedy rice. Population structure and principal component analyses showed no obvious difference in the genetic backgrounds of landrace and weedy rice in mitochondrial genome level. Phylogenetic, population split, and haplotype network evaluations were suggestive of independent origins of the indica and japonica varieties. The origin of weedy rice is supposed to be more likely from cultivated rice rather than from wild rice in mitochondrial genome level.
The role of indoleamine 2,3-dioxygenase-aryl hydrocarbon receptor pathway in the TLR4-induced tolerogenic phenotype in human DCs
Authors: Salazar Fabián , Awuah Dennis , Negm Ola H. , Shakib Farouk , Ghaemmaghami Amir M.
Published: March 2017

A controlled inflammatory response is required for protection against infection, but persistent inflammation causes tissue damage. Dendritic cells (DCs) have a unique capacity to promote both inflammatory and anti-inflammatory processes. One key mechanism involved in DC-mediated immunosuppression is the expression of tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO). IDO has been implicated in diverse processes in health and disease but its role in endotoxin tolerance in human DCs is still controversial. Here we investigated the role of IDO in shaping DCs phenotype and function under endotoxin tolerance conditions. Our data show that TLR4 ligation in LPS-primed DCs, induced higher levels of both IDO isoforms together with the transcription factor aryl-hydrocarbon receptor (AhR), compared to unprimed controls. Additionally, LPS conditioning induced an anti-inflammatory phenotype in DCs - with an increase in IL-10 and higher expression of programmed death ligand (PD-L)1 and PD-L2 - which were partially dependent on IDO. Furthermore, we demonstrated that the AhR-IDO pathway was responsible for the preferential activation of non-canonical NF-κB pathway in LPS-conditioned DCs. These data provide new insight into the mechanisms of the TLR4-induced tolerogenic phenotype in human DCs, which can help the better understanding of processes involved in induction and resolution of chronic inflammation and tolerance.
Word meaning acquisition is reflected in brain potentials of isolated words
Authors: Kuipers Jan Rouke , Uminski Anastasia , Green Zoe , Hughes David , Aglietti Tommaso
Published: March 2017

Learning a new concept and corresponding word typically involves repeated exposure to the word in the same or a similar context until the link crystallizes in long term memory. Although electrophysiological indices of the result of learning are well documented, there is currently no measure of the process of conceptually-mediated learning itself. Here, we recorded event-related brain potentials from participants who read unfamiliar words presented in isolation followed by a definition that either explained the meaning of the word or was a true, but uninformative statement. Self-reported word knowledge ratings increased for those words that were followed by meaningful definitions and were correlated with a decrease in ERP amplitude of a late frontal negativity (LFN) elicited by the isolated word. Importantly, the rate of LFN amplitude change predicted post-hoc learning outcome measures. Therefore, the LFN is real-time measure that is not under conscious control and which reflects conceptually-mediated learning. We propose that the LFN provides for the first time the opportunity to assess learning during study.
The Expanding Family of Natural Anion Channelrhodopsins Reveals Large Variations in Kinetics, Conductance, and Spectral Sensitivity
Authors: Govorunova Elena G. , Sineshchekov Oleg A. , Rodarte Elsa M. , Janz Roger , Morelle Olivier , Melkonian Michael , Wong Gane K.-S. , Spudich John L.
Published: March 2017

Natural anion channelrhodopsins (ACRs) discovered in the cryptophyte alga Guillardia theta generate large hyperpolarizing currents at membrane potentials above the Nernst equilibrium potential for Cl− and thus can be used as efficient inhibitory tools for optogenetics. We have identified and characterized new ACR homologs in different cryptophyte species, showing that all of them are anion-selective, and thus expanded this protein family to 20 functionally confirmed members. Sequence comparison of natural ACRs and engineered Cl−-conducting mutants of cation channelrhodopsins (CCRs) showed radical differences in their anion selectivity filters. In particular, the Glu90 residue in channelrhodopsin 2, which needed to be mutated to a neutral or alkaline residue to confer anion selectivity to CCRs, is nevertheless conserved in all of the ACRs identified. The new ACRs showed a large variation of the amplitude, kinetics, and spectral sensitivity of their photocurrents. A notable variant, designated “ZipACR”, is particularly promising for inhibitory optogenetics because of its combination of larger current amplitudes than those of previously reported ACRs and an unprecedentedly fast conductance cycle (current half-decay time 2–4 ms depending on voltage). ZipACR expressed in cultured mouse hippocampal neurons enabled precise photoinhibition of individual spikes in trains of up to 50 Hz frequency.
V2O5 encapsulated MWCNTs in 2D surface architecture: Complete solid-state bendable highly stabilized energy efficient supercapacitor device
Authors: Pandit Bidhan , Dubal Deepak P. , Gómez-Romero Pedro , Kale Bharat B. , Sankapal Babasaheb R.
Published: March 2017

A simple and scalable approach has been reported for V2O5 encapsulation over interconnected multi-walled carbon nanotubes (MWCNTs) network using chemical bath deposition method. Chemically synthesized V2O5/MWCNTs electrode exhibited excellent charge-discharge capability with extraordinary cycling retention of 93% over 4000 cycles in liquid-electrolyte. Electrochemical investigations have been performed to evaluate the origin of capacitive behavior from dual contribution of surface-controlled and diffusion-controlled charge components. Furthermore, a complete flexible solid-state, flexible symmetric supercapacitor (FSS-SSC) device was assembled with V2O5/MWCNTs electrodes which yield remarkable values of specific power and energy densities along with enhanced cyclic stability over liquid configuration. As a practical demonstration, the constructed device was used to lit the ‘VNIT’ acronym assembled using 21 LED’s.
Hydraulic forces contribute to left ventricular diastolic filling
Authors: Maksuti Elira , Carlsson Marcus , Arheden Håkan , Kovács Sándor J. , Broomé Michael , Ugander Martin
Published: March 2017

Myocardial active relaxation and restoring forces are known determinants of left ventricular (LV) diastolic function. We hypothesize the existence of an additional mechanism involved in LV filling, namely, a hydraulic force contributing to the longitudinal motion of the atrioventricular (AV) plane. A prerequisite for the presence of a net hydraulic force during diastole is that the atrial short-axis area (ASA) is smaller than the ventricular short-axis area (VSA). We aimed (a) to illustrate this mechanism in an analogous physical model, (b) to measure the ASA and VSA throughout the cardiac cycle in healthy volunteers using cardiovascular magnetic resonance imaging, and (c) to calculate the magnitude of the hydraulic force. The physical model illustrated that the anatomical difference between ASA and VSA provides the basis for generating a hydraulic force during diastole. In volunteers, VSA was greater than ASA during 75–100% of diastole. The hydraulic force was estimated to be 10–60% of the peak driving force of LV filling (1–3 N vs 5–10 N). Hydraulic forces are a consequence of left heart anatomy and aid LV diastolic filling. These findings suggest that the relationship between ASA and VSA, and the associated hydraulic force, should be considered when characterizing diastolic function and dysfunction.
Monomeric, porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro
Authors: Tamaddon M. , Burrows M. , Ferreira S. A. , Dazzi F. , Apperley J. F. , Bradshaw A. , Brand D. D. , Czernuszka J. , Gentleman E.
Published: March 2017

Osteoarthritis (OA) is a common cause of pain and disability and is often associated with the degeneration of articular cartilage. Lesions to the articular surface, which are thought to progress to OA, have the potential to be repaired using tissue engineering strategies; however, it remains challenging to instruct cell differentiation within a scaffold to produce tissue with appropriate structural, chemical and mechanical properties. We aimed to address this by driving progenitor cells to adopt a chondrogenic phenotype through the tailoring of scaffold composition and physical properties. Monomeric type-I and type-II collagen scaffolds, which avoid potential immunogenicity associated with fibrillar collagens, were fabricated with and without chondroitin sulfate (CS) and their ability to stimulate the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells was assessed. Immunohistochemical analyses showed that cells produced abundant collagen type-II on type-II scaffolds and collagen type-I on type-I scaffolds. Gene expression analyses indicated that the addition of CS – which was released from scaffolds quickly – significantly upregulated expression of type II collagen, compared to type-I and pure type-II scaffolds. We conclude that collagen type-II and CS can be used to promote a more chondrogenic phenotype in the absence of growth factors, potentially providing an eventual therapy to prevent OA.
Promoting in vivo remyelination with small molecules: a neuroreparative pharmacological treatment for Multiple Sclerosis
Authors: Medina-Rodríguez Eva María , Bribián Ana , Boyd Amanda , Palomo Valle , Pastor Jesús , Lagares Alfonso , Gil Carmen , Martínez Ana , Williams Anna , de Castro Fernando
Published: March 2017

Multiple Sclerosis (MS) is a neurodegenerative disease where immune-driven demyelination occurs with inefficient remyelination, but therapies are limited, especially those to enhance repair. Here, we show that the dual phosphodiesterase (PDE)7- glycogen synthase kinase (GSK)3 inhibitor, VP3.15, a heterocyclic small molecule with good pharmacokinetic properties and safety profile, improves in vivo remyelination in mouse and increases both adult mouse and adult human oligodendrocyte progenitor cell (OPC) differentiation, in addition to its immune regulatory action. The dual inhibition is synergistic, as increasing intracellular levels of cAMP by cyclic nucleotide PDE inhibition both suppresses the immune response and increases remyelination, and in addition, inhibition of GSK3 limits experimental autoimmune encephalomyelitis in mice. This combination of an advantageous effect on the immune response and an enhancement of repair, plus demonstration of its activity on adult human OPCs, leads us to propose dual PDE7-GSK3 inhibition, and specifically VP3.15, as a neuroprotective and neuroreparative disease-modifying treatment for MS.
Cryptic diversity in Tranzscheliella spp. (Ustilaginales) is driven by host switches
Authors: Li Ying-Ming , Shivas Roger G. , Cai Lei
Published: March 2017

Species of Tranzscheliella have been reported as pathogens of more than 30 genera of grasses (Poaceae). In this study, a combined morphological and molecular phylogenetic approach was used to examine 33 specimens provisionally identified as belonging to the T. hypodytes species complex. The phylogenetic analysis resolved several well-supported clades that corresponded to known and novel species of Tranzscheliella. Four new species are described and illustrated. In addition, a new combination in Tranzscheliella is proposed for Sorosporium reverdattoanum. Cophylogenetic analyses assessed by distance-based and event-cost based methods, indicated host switches are likely the prominent force driving speciation in Tranzscheliella.
PAR1 activation induces rapid changes in glutamate uptake and astrocyte morphology
Authors: Sweeney Amanda M. , Fleming Kelsey E. , McCauley John P. , Rodriguez Marvin F. , Martin Elliot T. , Sousa Alioscka A. , Leapman Richard D. , Scimemi Annalisa
Published: March 2017

The G-protein coupled, protease-activated receptor 1 (PAR1) is a membrane protein expressed in astrocytes. Fine astrocytic processes are in tight contact with neurons and blood vessels and shape excitatory synaptic transmission due to their abundant expression of glutamate transporters. PAR1 is proteolytically-activated by bloodstream serine proteases also involved in the formation of blood clots. PAR1 activation has been suggested to play a key role in pathological states like thrombosis, hemostasis and inflammation. What remains unclear is whether PAR1 activation also regulates glutamate uptake in astrocytes and how this shapes excitatory synaptic transmission among neurons. Here we show that, in the mouse hippocampus, PAR1 activation induces a rapid structural re-organization of the neuropil surrounding glutamatergic synapses, which is associated with faster clearance of synaptically-released glutamate from the extracellular space. This effect can be recapitulated using realistic 3D Monte Carlo reaction-diffusion simulations, based on axial scanning transmission electron microscopy (STEM) tomography reconstructions of excitatory synapses. The faster glutamate clearance induced by PAR1 activation leads to short- and long-term changes in excitatory synaptic transmission. Together, these findings identify PAR1 as an important regulator of glutamatergic signaling in the hippocampus and a possible target molecule to limit brain damage during hemorrhagic stroke.
Multimodal discrimination of immune cells using a combination of Raman spectroscopy and digital holographic microscopy
Authors: McReynolds Naomi , Cooke Fiona G. M. , Chen Mingzhou , Powis Simon J. , Dholakia Kishan
Published: March 2017

The ability to identify and characterise individual cells of the immune system under label-free conditions would be a significant advantage in biomedical and clinical studies where untouched and unmodified cells are required. We present a multi-modal system capable of simultaneously acquiring both single point Raman spectra and digital holographic images of single cells. We use this combined approach to identify and discriminate between immune cell populations CD4+ T cells, B cells and monocytes. We investigate several approaches to interpret the phase images including signal intensity histograms and texture analysis. Both modalities are independently able to discriminate between cell subsets and dual-modality may therefore be used a means for validation. We demonstrate here sensitivities achieved in the range of 86.8% to 100%, and specificities in the range of 85.4% to 100%. Additionally each modality provides information not available from the other providing both a molecular and a morphological signature of each cell.
Multi-mode of Four and Six Wave Parametric Amplified Process
Authors: Zhu Dayu , Yang Yiheng , Zhang Da , Liu Ruizhou , Ma Danmeng , Li Changbiao , Zhang Yanpeng
Published: March 2017

Multiple quantum modes in correlated fields are essential for future quantum information processing and quantum computing. Here we report the generation of multi-mode phenomenon through parametric amplified four- and six-wave mixing processes in a rubidium atomic ensemble. The multi-mode properties in both frequency and spatial domains are studied. On one hand, the multi-mode behavior is dominantly controlled by the intensity of external dressing effect, or nonlinear phase shift through internal dressing effect, in frequency domain; on the other hand, the multi-mode behavior is visually demonstrated from the images of the biphoton fields directly, in spatial domain. Besides, the correlation of the two output fields is also demonstrated in both domains. Our approach supports efficient applications for scalable quantum correlated imaging.
McMYB12 Transcription Factors Co-regulate Proanthocyanidin and Anthocyanin Biosynthesis in Malus Crabapple
Authors: Tian Ji , Zhang Jie , Han Zhen-yun , Song Ting-ting , Li Jin-yan , Wang Ya-ru , Yao Yun-cong
Published: March 2017

The flavonoid compounds, proanthocyanidins (PAs), protect plants from biotic stresses, contribute to the taste of many fruits, and are beneficial to human health in the form of dietary antioxidants. In this study, we functionally characterized two Malus crabapple R2R3-MYB transcription factors, McMYB12a and McMYB12b, which co-regulate PAs and anthocyanin biosynthesis. McMYB12a was shown to be mainly responsible for upregulating the expression of anthocyanin biosynthetic genes by binding to their promoters, but to be only partially responsible for regulating PAs biosynthetic genes. In contrast, McMYB12b showed preferential binding to the promoters of PAs biosynthetic genes. Overexpression of McMYB12a and McMYB12b in tobacco (Nicotiana tabacum) altered the expression of flavonoid biosynthetic genes and promoted the accumulation of PAs and anthocyanins in tobacco petals. Conversely, transient silencing their expression in crabapple plants, using a conserved gene region, resulted in reduced PAs and anthocyanin production a green leaf phenotype. Meanwhile, transient overexpression of the two genes and silenced McMYB12s in apple (Malus domestica) fruit had a similar effect as overexpression in tobacco and silenced in crabapple. This study reveals a new mechanism for the coordinated regulation of PAs and anthocyanin accumulation in crabapple leaves, which depends on an auto-regulatory balance involving McMYB12a and McMYB12b expression.
bta-miR-23a involves in adipogenesis of progenitor cells derived from fetal bovine skeletal muscle
Authors: Guan Long , Hu Xin , Liu Li , Xing Yishen , Zhou Zhengkui , Liang Xingwei , Yang Qiyuan , Jin Shengyun , Bao Jinshan , Gao Huijiang , Du Min , Li Junya , Zhang Lupei
Published: March 2017

Intramuscular fat deposition or marbling is essential for high quality beef. The molecular mechanism of adipogenesis in skeletal muscle remains largely unknown. In this study, we isolated Platelet-derived growth factor receptor α (PDGFRα) positive progenitor cells from fetal bovine skeletal muscle and induced into adipocytes. Using miRNAome sequencing, we revealed that bta-miR-23a was an adipogenic miRNA mediating bovine adipogenesis in skeletal muscle. The expression of bta-miR-23a was down-regulated during differentiation of PDGFRα+ progenitor cells. Forced expression of bta-miR-23a mimics reduced lipid accumulation and inhibited the key adipogenic transcription factor peroxisome proliferative activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha (C/EBPα). Whereas down-regulation of bta-miR-23a by its inhibitors increased lipid accumulation and expression of C/EBPα, PPARγ and fatty acid-binding protein 4 (FABP4). Target prediction analysis revealed that ZNF423 was a potential target of bta-miR-23a. Dual-luciferase reporter assay revealed that bta-miR-23a directly targeted the 3′-UTR of ZNF423. Together, our data showed that bta-miR-23a orchestrates early intramuscular adipogeneic commitment as an anti-adipogenic regulator which acts by targeting ZNF423.
The genome of Leishmania adleri from a mammalian host highlights chromosome fission in Sauroleishmania
Authors: Coughlan Simone , Mulhair Peter , Sanders Mandy , Schonian Gabriele , Cotton James A. , Downing Tim
Published: March 2017

Control of pathogens arising from humans, livestock and wild animals can be enhanced by genome-based investigation. Phylogenetically classifying and optimal construction of these genomes using short sequence reads are key to this process. We examined the mammal-infecting unicellular parasite Leishmania adleri belonging to the lizard-infecting Sauroleishmania subgenus. L. adleri has been associated with cutaneous disease in humans, but can be asymptomatic in wild animals. We sequenced, assembled and investigated the L. adleri genome isolated from an asymptomatic Ethiopian rodent (MARV/ET/75/HO174) and verified it as L. adleri by comparison with other Sauroleishmania species. Chromosome-level scaffolding was achieved by combining reference-guided with de novo assembly followed by extensive improvement steps to produce a final draft genome with contiguity comparable with other references. L. tarentolae and L. major genome annotation was transferred and these gene models were manually verified and improved. This first high-quality draft Leishmania adleri reference genome is also the first Sauroleishmania genome from a non-reptilian host. Comparison of the L. adleri HO174 genome with those of L. tarentolae Parrot-TarII and lizard-infecting L. adleri RLAT/KE/1957/SKINK-7 showed extensive gene amplifications, pervasive aneuploidy, and fission of chromosomes 30 and 36. There was little genetic differentiation between L. adleri extracted from mammals and reptiles, highlighting challenges for leishmaniasis surveillance.
The alr-groEL1 operon in Mycobacterium tuberculosis: an interplay of multiple regulatory elements
Authors: Bhat Aadil H. , Pathak Deepika , Rao Alka
Published: March 2017

Threonylcarbamoyladenosine is a universally conserved essential modification of tRNA that ensures translational fidelity in cellular milieu. TsaD, TsaB and TsaE are identified as tRNA-A37-threonylcarbamoyl (t6A)-transferase enzymes that have been reconstituted in vitro, in few bacteria recently. However, transcriptional organization and regulation of these genes are not known in any of these organisms. This study describes the intricate architecture of a complex multicistronic alr-groEL1 operon, harboring essential genes, namely tsaD, tsaB, tsaE, groES, groEL1, and alr (required for cell wall synthesis), and rimI encoding an N-α- acetyltransferase in Mycobacterium tuberculosis. Using northern blotting, RT-PCR and in vivo fluorescence assays, genes alr to groEL1 were found to constitute an ~6.3 kb heptacistronic operon with multiple internal promoters and an I-shaped intrinsic hairpin-like cis-regulatory element. A strong promoter PtsaD within the coding sequence of rimI gene is identified in M. tuberculosis, in addition. The study further proposes an amendment in the known bicistronic groESL1 operon annotation by providing evidence that groESL1 is co-transcribed as sub-operon of alr-groEL1 operon. The architecture of alr-groEL1 operon, conservation of the genetic context and a mosaic transcriptional profile displayed under various stress conditions convincingly suggest the involvement of this operon in stress adaptation in M. tuberculosis.
Empty-nest-related psychological distress is associated with progression of brain white matter lesions and cognitive impairment in the elderly
Authors: Duan Dandan , Dong Yuanli , Zhang Hua , Zhao Yingxin , Diao Yutao , Cui Yi , Wang Juan , Chai Qiang , Liu Zhendong
Published: March 2017

This study evaluated the association between empty-nest-related psychological distress and the progression of white matter lesions (WMLs) and cognitive impairment in 219 elderly subjects aged 60 years or over. Psychological distress was assessed using the University of California at Los Angeles Loneliness Scale (UCLA-LS) and Geriatric Depression Scale (GDS) Short-Form. Cognitive function was evaluated using the MMSE and MoCA. White matter hyperintensities (WMH) were assessed using magnetic resonance imaging. After 5.2-year follow-up, the reductions in MMSE and MoCA scores and the increases in periventricular (P)WMH, deep (D)WMH, and total WMH volumes in the empty-nest elderly were greater than those in the non-empty-nest elderly (P < 0.05). The reduced MMSE and MoCA scores and increased volumes of PWMH and total WMH in the empty-nest elderly living alone were greater than those in the empty-nest elderly living with a spouse (P < 0.05). UCLA-LS and GDS scores were significantly and independently associated with reduced MMSE and MoCA scores and the increased volumes of PWMH, DWMH, and total WMH. The results indicate that empty-nest-related psychological distress is associated with progression of WMLs and cognitive impairment in the elderly.
Prognosis and Progression of ESCC Patients with Perineural Invasion
Authors: Xu Guanghui , Feng Fan , Liu Zhen , Liu Shushang , Zheng Gaozan , Xiao Shuao , Cai Lei , Yang Xuewen , Li Guocai , Lian Xiao , Guo Man , Sun Li , Yang Jianjun , Fan Daiming , Lu Qun , Zhang Hongwei
Published: March 2017

Perineural invasion (PNI) has been recognized as a poor prognostic factor in several malignancies, but the definition and pathogenesis of PNI in esophageal squamous cell carcinoma (ESCC) remains to be defined. PNI was evaluated by H&E staining and S100 immunohistochemistry. The predictive value of PNI in the prognosis of ESCC patients was analyzed. PNI was evaluated in vitro and in vivo. A total of 54 specimens (17.88%) were defined as PNI-a and 99 specimens (32.78%) as PNI-b. S100 staining was superior to H&E staining for PNI detection (50.66% vs 27.15%, P < 0.001, κ = 0.506). Tumor depth (P = 0.001), tumor stage (P = 0.010), and vascular invasion (P < 0.001) were significantly associated with PNI. PIN-a and PNI-b had significant lower disease free survival (DFS) and disease specific survival (DSS) than PNI-0 patients, and the prognosis of PNI-b patients was significantly worse than PNI-a patients for DFS (P = 0.009). PNI was an independent predictor for DFS and DSS in ESCC as evaluated by univariate and multivariate analyses. ESCC cells could metastasize along the nerve in vitro and in vivo, and PNI was a dynamic process. S100 staining significantly improved the accuracy of PNI detection. PNI was associated with local recurrence and poor prognosis of ESCC patients.
CD61 promotes the differentiation of canine ADMSCs into PGC-like cells through modulation of TGF-β signaling
Authors: Fang Jia , Wei Yudong , Lv Changrong , Peng Sha , Zhao Shanting , Hua Jinlian
Published: March 2017

Previous studies have shown that CD61 (integrin-β3) promotes the differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) into germ-like cells. However, the mechanism remains unclear. In this study, we showed that overexpression of CD61 in canine adipose-derived mesenchymal stem cells (cADMSCs) promotes their differentiation into primordial germ cell (PGC)-like cells. Quantitative real-time PCR, immunocytochemistry and western blot detected higher levels of PGC-specific markers in CD61-overexpressed cADMSCs compared with those in control cells. Moreover, phosphorylation of Smad2, a downstream mediator of transforming growth factor beta (TGF-β), was increased in CD61-overexpressed cADMSCs than that in control cells. However, the expression of PGC-specific markers was downregulated in cADMSCs treated with a TGF-β inhibitor. These results suggested that CD61 could induce cADMSCs to differentiate into PGC-like cells by relying on the activation of TGF-β pathway. ADMSCs possess a considerable potential in treating the infertility of rare animal species.
Proline dehydrogenase from Thermus thermophilus does not discriminate between FAD and FMN as cofactor
Authors: Huijbers Mieke M. E. , Martínez-Júlvez Marta , Westphal Adrie H. , Delgado-Arciniega Estela , Medina Milagros , van Berkel Willem J. H.
Published: March 2017

Flavoenzymes are versatile biocatalysts containing either FAD or FMN as cofactor. FAD often binds to a Rossmann fold, while FMN prefers a TIM-barrel or flavodoxin-like fold. Proline dehydrogenase is denoted as an exception: it possesses a TIM barrel-like fold while binding FAD. Using a riboflavin auxotrophic Escherichia coli strain and maltose-binding protein as solubility tag, we produced the apoprotein of Thermus thermophilus ProDH (MBP-TtProDH). Remarkably, reconstitution with FAD or FMN revealed that MBP-TtProDH has no preference for either of the two prosthetic groups. Kinetic parameters of both holo forms are similar, as are the dissociation constants for FAD and FMN release. Furthermore, we show that the holo form of MBP-TtProDH, as produced in E. coli TOP10 cells, contains about three times more FMN than FAD. In line with this flavin content, the crystal structure of TtProDH variant ΔABC, which lacks helices αA, αB and αC, shows no electron density for an AMP moiety of the cofactor. To the best of our knowledge, this is the first example of a flavoenzyme that does not discriminate between FAD and FMN as cofactor. Therefore, classification of TtProDH as an FAD-binding enzyme should be reconsidered.
Shrubland primary production and soil respiration diverge along European climate gradient
Authors: Reinsch Sabine , Koller Eva , Sowerby Alwyn , de Dato Giovanbattista , Estiarte Marc , Guidolotti Gabriele , Kovács-Láng Edit , Kröel-Dulay György , Lellei-Kovács Eszter , Larsen Klaus S. , Liberati Dario , Peñuelas Josep , Ransijn Johannes , Robinson David A. , Schmidt Inger K. , Smith Andrew R. , Tietema Albert , Dukes Jeffrey S. , Beier Claus , Emmett Bridget A.
Published: March 2017

Above- and belowground carbon (C) stores of terrestrial ecosystems are vulnerable to environmental change. Ecosystem C balances in response to environmental changes have been quantified at individual sites, but the magnitudes and directions of these responses along environmental gradients remain uncertain. Here we show the responses of ecosystem C to 8–12 years of experimental drought and night-time warming across an aridity gradient spanning seven European shrublands using indices of C assimilation (aboveground net primary production: aNPP) and soil C efflux (soil respiration: Rs). The changes of aNPP and Rs in response to drought indicated that wet systems had an overall risk of increased loss of C but drier systems did not. Warming had no consistent effect on aNPP across the climate gradient, but suppressed Rs more at the drier sites. Our findings suggest that above- and belowground C fluxes can decouple, and provide no evidence of acclimation to environmental change at a decadal timescale. aNPP and Rs especially differed in their sensitivity to drought and warming, with belowground processes being more sensitive to environmental change.
Volatile metabolomic signature of human breast cancer cell lines
Authors: Silva Catarina L. , Perestrelo Rosa , Silva Pedro , Tomás Helena , Câmara José S.
Published: March 2017

Breast cancer (BC) remains the most prevalent oncologic pathology in women, causing huge psychological, economic and social impacts on our society. Currently, the available diagnostic tools have limited sensitivity and specificity. Metabolome analysis has emerged as a powerful tool for obtaining information about the biological processes that occur in organisms, and is a useful platform for discovering new biomarkers or make disease diagnosis using different biofluids. Volatile organic compounds (VOCs) from the headspace of cultured BC cells and normal human mammary epithelial cells, were collected by headspace solid-phase microextraction (HS-SPME) and analyzed by gas chromatography combined with mass spectrometry (GC–MS), thus defining a volatile metabolomic signature. 2-Pentanone, 2-heptanone, 3-methyl-3-buten-1-ol, ethyl acetate, ethyl propanoate and 2-methyl butanoate were detected only in cultured BC cell lines. Multivariate statistical methods were used to verify the volatomic differences between BC cell lines and normal cells in order to find a set of specific VOCs that could be associated with BC, providing comprehensive insight into VOCs as potential cancer biomarkers. The establishment of the volatile fingerprint of BC cell lines presents a powerful approach to find endogenous VOCs that could be used to improve the BC diagnostic tools and explore the associated metabolomic pathways.
Hyaluronic acid-functionalized electrospun PLGA nanofibers embedded in a microfluidic chip for cancer cell capture and culture
Authors: Xu Gangwei , Tan Yulong , Xu Tiegang , Yin Di , Wang Mengyuan , Shen Mingwu , Chen Xiaofeng , Shi Xiangyang , Zhu Xiaoyue
Published: March 2017

Hyaluronic acid-functionalized electrospun PLGA nanofibers embedded in a microfluidic chip are able to effectively capture cancer cells.
Atomic structure of Mg-based metallic glasses from molecular dynamics and neutron diffraction
Authors: Gulenko Anastasia , Forto Chungong Louis , Gao Junheng , Todd Iain , Hannon Alex C. , Martin Richard A. , Christie Jamieson K.
Published: March 2017

We use a combination of classical molecular dynamics simulation and neutron diffraction to identify the atomic structure of five different Mg–Zn–Ca bulk metallic glasses, covering a range of compositions with substantially different behaviour when implantedin vitro.
Dangerous liaisons: anion-induced protonation in phosphate–polyamine interactions and their implications for the charge states of biologically relevant surfaces
Authors: Laucirica Gregorio , Marmisollé Waldemar A. , Azzaroni Omar
Published: March 2017

The specific binding of phosphates on surface amino groups has complex consequences on the protonation equilibriums and effective surface charges with serious implications for further biochemically relevant interactions.
Theoretical and experimental examination of SFG polarization analysis at acetonitrile–water solution surfaces
Authors: Saito Kengo , Peng Qiling , Qiao Lin , Wang Lin , Joutsuka Tatsuya , Ishiyama Tatsuya , Ye Shen , Morita Akihiro
Published: March 2017

Polarization analysis of SFG spectroscopy is thoroughly examined in collaboration of SFG measurements and MD simulations.
Exceptional sorption behaviour of porous tungsten oxide for aqueous lead
Authors: Perkins Cory K. , Reed Travis M. , Brown Zachary A. , Apblett Allen W.
Published: March 2017

A nanoporous WO3sorbent was found to be highly reactive towards Pb2+, exhibiting a molar sorption capacity of 42.5% and sorption half-lives as low as 47 s.
Facile preparation of Ag/Ni(OH)2 composites with enhanced catalytic activity for reduction of 4-nitrophenol
Authors: Bao Feng , Tan Fatang , Wang Wei , Qiao Xueliang , Chen Jianguo
Published: March 2017

Preparation and formation mechanism of Ag/Ni(OH)2 composites with enhanced catalytic activity for reduction of 4-nitrophenol were systematically studied.
Effects of microwaves on molecular arrangements in potato starch
Authors: Shen Huijie , Fan Daming , Huang Luelue , Gao Yishu , Lian Huizhang , Zhao Jianxin , Zhang Hao
Published: March 2017

The effects of microwave heating on the molecular arrangements in potato starch, including single and double helices and amorphous structures, were studied using a 13C CP/MAS NMR method combined with X-ray diffraction.
Highly efficient adsorbent design using a Cu-BTC/CuO/carbon fiber paper composite for high CH4/N2 selectivity
Authors: Qu Zhi-Guo , Wang Hui , Zhang Wen
Published: March 2017

Cu-BTC/CuO/CFP, which was obtained via atomic layer deposition, has higher selectivity for CH4/N2, temperature uniformity, and lower pressure drop compared to Cu-BTC.
Tuning the surface chemistry of graphene flakes: new strategies for selective oxidation
Authors: Araújo Mariana P. , Soares O. S. G. P. , Fernandes A. J. S. , Pereira M. F. R. , Freire C.
Published: March 2017

One-step selective oxidation strategies towards the rational tuning of the surface chemistry of graphene flakes are presented.
Exhaustive Suzuki–Miyaura reactions of polyhalogenated heteroarenes with alkyl boronic pinacol esters
Authors: Laulhé Sébastien , Blackburn J. Miles , Roizen Jennifer L.
Published: March 2017

A novel Suzuki–Miyaura protocol is described that enables the exhaustive alkylation of polychlorinated pyridines.
New complexity for aromatic ring agostic interactions
Authors: Sajjad M. Arif , Christensen Kirsten E. , Rees Nicholas H. , Schwerdtfeger Peter , Harrison John A. , Nielson Alastair J.
Published: March 2017

Aromatic ring agostic interactions can be augmented by previously unrecognised CCπ to metal donation which has significant implication for ligand-assisted C–H bond functionalization.
Spin–orbit coupling in nearly metallic chiral carbon nanotubes: a density-functional based study
Authors: Maslyuk Volodymyr V. , Gutierrez Rafael , Cuniberti Gianaurelio
Published: March 2017

An accurate implementation of spin–orbit interactions in a density-functional theory framework is presented, including both core and valence orbital contributions, thus encompassing the full system potential.
Room-temperature phosphorescence from small organic systems containing a thiocarbonyl moiety
Authors: Huang Chun-Hao , Wu Pei-Jhen , Chung Kun-You , Chen Yi-An , Li Elise Y. , Chou Pi-Tai
Published: March 2017

Room-temperature phosphorescence facilitated by the thiocarbonyl group in dTPT3-based derivatives.
Pressure inverse solubility and polymorphism of an edible γ-cyclodextrin-based metal–organic framework
Authors: Patyk-Kaźmierczak Ewa , Warren Mark R. , Allan David R. , Katrusiak Andrzej
Published: March 2017

An edible metal–organic framework, γ-CD-MOF-1, has been obtained in a new trigonal form. The γ-CD-MOF-1 high-pressure dissolution as well as the cubic and trigonal polymorphs are closely related and regulated by the guest framework interactions and adsorption in the pores.
High level potential energy surface and mechanism of Al(CH3)2OCH3-promoted lactone polymerization: initiation and propagation
Authors: Vogt-Geisse Stefan , Mata Ricardo A. , Toro-Labbé Alejandro
Published: March 2017

A hitherto unreported, second transition state (TS2) is the stationary state with the highest relative energy of the Al(CH3)2OCH3 + glycolide initiation reaction.
Iron–cobalt bimetal oxide nanorods as efficient and robust water oxidation catalysts
Authors: Zhou Xichen , Huang Jingwei , Zhang Fuming , Zhao Yukun , Zhang Yan , Ding Yong
Published: March 2017

Iron–cobalt bimetal oxide nanorods (Fe1.1Co1.9O4) can efficiently catalyze water oxidation under the reaction conditions of photocatalytic and electrochemical. This superior photocatalytic performance owes to the best balanced flat-band potential of Fe1.1Co1.9O4.
Comparative solution equilibrium studies of antitumor ruthenium(η6-p-cymene) and rhodium(η5-C5Me5) complexes of 8-hydroxyquinolines
Authors: Dömötör Orsolya , Pape Veronika F. S. , May Nóra V. , Szakács Gergely , Enyedy Éva A.
Published: March 2017

Solution stability, chloride ion affinity and multidrug resistance selectivity of half-sandwich Rh(η5-C5Me5) and Ru(η6-p-cymene) complexes of 8-hydroxyquinolines.
A fast and fit-for-purpose arsenic speciation method for wine and rice
Authors: Gray Patrick J. , Tanabe Courtney K. , Ebeler Susan E. , Nelson Jenny
Published: March 2017

We report a 2 minute chromatographic method for arsenic speciation in rice and wine with validation data.
Repairable photoactive polymer systems via metal–terpyridine-based self-assembly
Authors: Jeong Dong-Cheol , Lee Jookyeong , Ro Yu Hyeon , Song Changsik
Published: March 2017

The photocatalytic activity of polymeric systems ceased upon disassembly and was restored upon assembly through metal ion–ligand interaction.
Upconversion luminescence of Sm2+ ions
Authors: Liu Xiaohui , Aidilibike Tuerxun , Guo Junjie , Li Yangyang , Di Weihua , Qin Weiping
Published: March 2017

Herein, we report the phenomenon of upconversion luminescence from Sm2+ ions, which demonstrates that changeable valence lanthanides can serve as ions for optical frequency transformation.
Hydrolysis and condensation of a benzocyclobutene-functionalized precursor for the synthesis of high performance low-K polymers
Authors: Cheng Yuanrong , Chen Wenhao , Li Zhuo , Zhu Tangwei , Zhang Ziyu , Jin Yunxia
Published: March 2017

A new synthetic route involving the hydrolysis and condensation of a BCB precursor for high performance low-Kbenzocyclobutene-functionalized polymers was developed.
Binuclear alkynylplatinum(ii) terpyridine complexes with flexible bridges behave as organogelators for several organic solvents
Authors: Xing Ling-Bao , Qiao Fei , Yuan Zhao , Zhang Jing-Li , Zhang Rui-Ying , Zhuo Shuping , Zhou Zi-Yan
Published: March 2017

New binuclear alkynylplatinum(ii) terpyridyl complexes with flexible bridges have been synthesized and characterized by 1H NMR, mass spectra and elemental analysis.
Copper loaded on activated carbon as an efficient adsorbent for removal of methylene blue
Authors: Shu Jianhua , Cheng Song , Xia Hongying , Zhang Libo , Peng Jinhui , Li Chunyang , Zhang Shengzhou
Published: March 2017

Copper loaded activated carbon (Cu-AC) was prepared by impregnating it with cupric nitrate followed by microwave heating and then used for removing dyes in wastewater.
High conversion of glucose to 5-hydroxymethylfurfural using hydrochloric acid as a catalyst and sodium chloride as a promoter in a water/γ-valerolactone system
Authors: Li Minghao , Li Wenzhi , Lu Yijuan , Jameel Hasan , Chang Hou-min , Ma Longlong
Published: March 2017

HCl as a catalyst and NaCl as a promoter result in impressive selectivity and HMF yield in a water/γ-valerolactone system.