bluuebunny/crossref_metadata_2025 huggingface dataset:
Florpyrauxifen-benzyl Weed Control Spectrum and Tank-Mix Compatibility with other Commonly Applied Herbicides in Rice
Authors: Miller M. Ryan , Norsworthy Jason K.
Published: February 2018

Florpyrauxifen-benzyl is a new herbicide being developed for rice. Research is needed to understand its spectrum of control and optimal tank-mix partners. Multiple greenhouse and field experiments were conducted to evaluate florpyrauxifen-benzyl efficacy and tank-mix compatibility. In greenhouse experiments, florpyrauxifen-benzyl at 30 g ai ha–1provided ≥75% control of all weed species evaluated (broadleaf signalgrass, barnyardgrass, Amazon sprangletop, large crabgrass, northern jointvetch, hemp sesbania, pitted morningglory, Palmer amaranth, yellow nutsedge, rice flatsedge, smallflower umbrellasedge), and control was similar to or better than other herbicide options currently available in rice. Barnyardgrass was controlled 97% with florpyrauxifen-benzyl at 30 g ha–1, ultimately reducing height (86%) and aboveground biomass (84%). In these field studies at 30 g ha–1, no antagonism was observed when florpyrauxifen-benzyl was tank-mixed with contact (acifluorfen, bentazon, carfentrazone, propanil, and saflufenacil) or systemic (2,4-D, bispyribac, cyhalofop, fenoxaprop, halosulfuron, imazethapyr, penoxsulam, quinclorac, and triclopyr) rice herbicides. Although not every tank-mix or weed species was evaluated, the lack of antagonistic interactions herein highlights the flexibility and versatility of this new herbicide. Once florpyrauxifen-benzyl becomes commercially available, it will be beneficial to tank-mix this new herbicide with others without sacrificing efficacy, so as to apply multiple sites of action together and thus lessen the risk for evolution of herbicide resistance.
Control of Photosystem II– and 4-Hydroxyphenylpyruvate Dioxygenase Inhibitor–Resistant Palmer Amaranth (Amaranthus palmeri) in Conventional Corn
Authors: Chahal Parminder S. , Irmak Suat , Gaines Todd , Amundsen Keenan , Jugulam Mithila , Jha Prashant , Travlos Ilias S. , Jhala Amit J.
Published: February 2018

Palmer amaranth, a dioecious summer annual weed species, is the most troublesome weed in agronomic crop production systems in the United States. Palmer amaranth resistant to photosystem (PS) II- and 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors is of particular concern in south central Nebraska. The objectives of this study were to determine the effect of PRE followed by POST herbicide programs on PS II- and HPPD-inhibitor-resistant Palmer amaranth control, crop yield, and net economic return in conventional corn. A field study was conducted in 2014, 2015, and 2016 in a grower’s field infested with PS II- and HPPD-inhibitor-resistant Palmer amaranth near Shickley in Fillmore County, Nebraska. A contrast analysis suggested that mesotrione+S-metolachlor+atrazine applied PRE provided 83% Palmer amaranth control at 21 d after application compared to 78 and 72% control with pyroxasulfone+fluthiacet-ethyl+atrazine and saflufenacil+dimethenamid-P, respectively. Most of the PRE followed by POST herbicide programs provided ≥85% Palmer amaranth control. Based on contrast analysis, POST application of dicamba+diflufenzopyr provided 93% Palmer amaranth control compared to 87, 79, and 42% control with dicamba, dicamba+halosulfuron, and acetochlor, respectively, at 28 d after POST. All PRE followed by POST herbicide programs, aside from mesotrione+S-metolachlor+atrazine followed by acetochlor (2,530 to 7,809 kg ha−1), provided 9,550 to 10,500 kg ha−1corn yield compared with 2,713 to 6,110 kg ha−1from nontreated control. Similarly, PRE followed by POST herbicide programs, except for mesotrione+S-metolachlor+atrazine followed by acetochlor ($191 and $897 ha−1), provided similar net return of $427 to $707 ha−1and $1,127 to $1,727 ha−1in 2014 and 2015-16, respectively. It is concluded that herbicide programs based on multiple sites of action are available for control of PS II- and HPPD-inhibitor-resistant Palmer amaranth in conventional corn.
ERPs Reveal Relationships Between Neural Orthographic Priming Effects and Reading Skill
Authors: Welcome Suzanne E. , Trammel Emma R.
Published: February 2018

Abstract. Masked priming has long been used to demonstrate the impact of brief presentations of orthographically related stimuli on visual word recognition. The aim of the present study was to examine neural correlates of orthographic priming produced by pronounceable and unpronounceable anagram primes. Crucially, we examined relationships between these priming effects and individual differences on a battery of measures assessing orthographic processing ability, current reading ability, and verbal intelligence in university students. Our study demonstrated group-level priming effects on the N200 and N400, with both components being primarily modulated by unpronounceable, orthographically illegal primes. Relationships between the extent of priming as indexed by N200 amplitude and speed of orthographic processing emerged, as reaction time (RT) on an orthographic choice task was associated with priming effects. Priming effects on N400 amplitude were related to phonological decoding efficiency. Those individuals with less efficient orthographic or phonological processing were more sensitive to the orthographic relationship between primes and targets. These findings demonstrate that university students vary in their sensitivity to orthographic priming and the degree to which orthographic information is used during word recognition.
Mycoplasma-related endobacteria within Mortierellomycotina fungi: diversity, distribution and functional insights into their lifestyle
Authors: Desirò Alessandro , Hao Zhen , Liber Julian A , Benucci Gian Maria Niccolò , Lowry David , Roberson Robert , Bonito Gregory
Published: February 2018

Bacterial interactions with animals and plants have been examined for over a century; by contrast, the study of bacterial–fungal interactions has received less attention. Bacteria interact with fungi in diverse ways, and endobacteria that reside inside fungal cells represent the most intimate interaction. The most significant bacterial endosymbionts that have been studied are associated with Mucoromycota and include two main groups: Burkholderia-related and Mycoplasma-related endobacteria (MRE). Examples of Burkholderia-related endobacteria have been reported in the three Mucoromycota subphyla. By contrast, MRE have only been identified in Glomeromycotina and Mucoromycotina. This study aims to understand whether MRE dwell in Mortierellomycotina and, if so, to determine their impact on the fungal host. We carried out a large-scale screening of 394 Mortierellomycotina strains and employed a combination of microscopy, molecular phylogeny, next-generation sequencing and qPCR. We detected MRE in 12 strains. These endosymbionts represent novel bacterial phylotypes and show evidence of recombination. Their presence in Mortierellomycotina demonstrates that MRE occur within fungi across Mucoromycota and they may have lived in their common ancestor. We cured the fungus of its endosymbionts with antibiotics and observed improved biomass production in isogenic lines lacking MRE, demonstrating that these endobacteria impose some fitness costs to their fungal host. Here we provided the first functional insights into the lifestyle of MRE. Our findings indicate that MRE may be antagonistic to their fungal hosts, and adapted to a non-lethal parasitic lifestyle in the mycelium of Mucoromycota. However, context-dependent adaptive benefits to their host at minimal cost cannot not be excluded. Finally, we conclude that Mortierellomycotina represent attractive model organisms for exploring interactions between MRE and fungi.
Elevated intracellular cAMP exacerbates vulnerability to oxidative stress in optic nerve head astrocytes
Authors: Shim Myoung Sup , Kim Keun-Young , Bu Jung Hyun , Nam Hye Seung , Jeong Seung Won , Park Tae Lim , Ellisman Mark H. , Weinreb Robert N. , Ju Won-Kyu
Published: February 2018

Glaucoma is characterized by a progressive loss of retinal ganglion cells and their axons, but the underlying biological basis for the accompanying neurodegeneration is not known. Accumulating evidence indicates that structural and functional abnormalities of astrocytes within the optic nerve head (ONH) have a role. However, whether the activation of cyclic adenosine 3′,5′-monophosphate (cAMP) signaling pathway is associated with astrocyte dysfunction in the ONH remains unknown. We report here that the cAMP/protein kinase A (PKA) pathway is critical to ONH astrocyte dysfunction, leading to caspase-3 activation and cell death via the AKT/Bim/Bax signaling pathway. Furthermore, elevated intracellular cAMP exacerbates vulnerability to oxidative stress in ONH astrocytes, and this may contribute to axonal damage in glaucomatous neurodegeneration. Inhibition of intracellular cAMP/PKA signaling activation protects ONH astrocytes by increasing AKT phosphorylation against oxidative stress. These results strongly indicate that activation of cAMP/PKA pathway has an important role in astrocyte dysfunction, and suggest that modulating cAMP/PKA pathway has therapeutic potential for glaucomatous ONH degeneration.
The mycotoxin phomoxanthone A disturbs the form and function of the inner mitochondrial membrane
Authors: Böhler Philip , Stuhldreier Fabian , Anand Ruchika , Kondadi Arun Kumar , Schlütermann David , Berleth Niklas , Deitersen Jana , Wallot-Hieke Nora , Wu Wenxian , Frank Marian , Niemann Hendrik , Wesbuer Elisabeth , Barbian Andreas , Luyten Tomas , Parys Jan B. , Weidtkamp-Peters Stefanie , Borchardt Andrea , Reichert Andreas S. , Peña-Blanco Aida , García-Sáez Ana J. , Itskanov Samuel , van der Bliek Alexander M. , Proksch Peter , Wesselborg Sebastian , Stork Björn
Published: February 2018

Mitochondria are cellular organelles with crucial functions in the generation and distribution of ATP, the buffering of cytosolic Ca2+ and the initiation of apoptosis. Compounds that interfere with these functions are termed mitochondrial toxins, many of which are derived from microbes, such as antimycin A, oligomycin A, and ionomycin. Here, we identify the mycotoxin phomoxanthone A (PXA), derived from the endophytic fungus Phomopsis longicolla, as a mitochondrial toxin. We show that PXA elicits a strong release of Ca2+ from the mitochondria but not from the ER. In addition, PXA depolarises the mitochondria similarly to protonophoric uncouplers such as CCCP, yet unlike these, it does not increase but rather inhibits cellular respiration and electron transport chain activity. The respiration-dependent mitochondrial network structure rapidly collapses into fragments upon PXA treatment. Surprisingly, this fragmentation is independent from the canonical mitochondrial fission and fusion mediators DRP1 and OPA1, and exclusively affects the inner mitochondrial membrane, leading to cristae disruption, release of pro-apoptotic proteins, and apoptosis. Taken together, our results suggest that PXA is a mitochondrial toxin with a novel mode of action that might prove a useful tool for the study of mitochondrial ion homoeostasis and membrane dynamics.
Evolution of Barrett’s esophagus through space and time at single-crypt and whole-biopsy levels
Authors: Martinez Pierre , Mallo Diego , Paulson Thomas G. , Li Xiaohong , Sanchez Carissa A. , Reid Brian J. , Graham Trevor A. , Kuhner Mary K. , Maley Carlo C.
Published: February 2018

The low risk of progression of Barrett’s esophagus (BE) to esophageal adenocarcinoma can lead to over-diagnosis and over-treatment of BE patients. This may be addressed through a better understanding of the dynamics surrounding BE malignant progression. Although genetic diversity has been characterized as a marker of malignant development, it is still unclear how BE arises and develops. Here we uncover the evolutionary dynamics of BE at crypt and biopsy levels in eight individuals, including four patients that experienced malignant progression. We assay eight individual crypts and the remaining epithelium by SNP array for each of 6–11 biopsies over 2 time points per patient (358 samples in total). Our results indicate that most Barrett’s segments are clonal, with similar number and inferred rates of alterations observed for crypts and biopsies. Divergence correlates with geographical location, being higher near the gastro-esophageal junction. Relaxed clock analyses show that genomic instability precedes and is enhanced by genome doubling. These results shed light on the clinically relevant evolutionary dynamics of BE.
Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis
Authors: Mizoguchi Fumitaka , Slowikowski Kamil , Wei Kevin , Marshall Jennifer L. , Rao Deepak A. , Chang Sook Kyung , Nguyen Hung N. , Noss Erika H. , Turner Jason D. , Earp Brandon E. , Blazar Philip E. , Wright John , Simmons Barry P. , Donlin Laura T. , Kalliolias George D. , Goodman Susan M. , Bykerk Vivian P. , Ivashkiv Lionel B. , Lederer James A. , Hacohen Nir , Nigrovic Peter A. , Filer Andrew , Buckley Christopher D. , Raychaudhuri Soumya , Brenner Michael B.
Published: February 2018

Fibroblasts regulate tissue homeostasis, coordinate inflammatory responses, and mediate tissue damage. In rheumatoid arthritis (RA), synovial fibroblasts maintain chronic inflammation which leads to joint destruction. Little is known about fibroblast heterogeneity or if aberrations in fibroblast subsets relate to pathology. Here, we show functional and transcriptional differences between fibroblast subsets from human synovial tissues using bulk transcriptomics of targeted subpopulations and single-cell transcriptomics. We identify seven fibroblast subsets with distinct surface protein phenotypes, and collapse them into three subsets by integrating transcriptomic data. One fibroblast subset, characterized by the expression of proteins podoplanin, THY1 membrane glycoprotein and cadherin-11, but lacking CD34, is threefold expanded in patients with RA relative to patients with osteoarthritis. These fibroblasts localize to the perivascular zone in inflamed synovium, secrete proinflammatory cytokines, are proliferative, and have an in vitro phenotype characteristic of invasive cells. Our strategy may be used as a template to identify pathogenic stromal cellular subsets in other complex diseases.
Bioinspired leaves-on-branchlet hybrid carbon nanostructure for supercapacitors
Authors: Xiong Guoping , He Pingge , Lyu Zhipeng , Chen Tengfei , Huang Boyun , Chen Lei , Fisher Timothy S.
Published: February 2018

Designing electrodes in a highly ordered structure simultaneously with appropriate orientation, outstanding mechanical robustness, and high electrical conductivity to achieve excellent electrochemical performance remains a daunting challenge. Inspired by the phenomenon in nature that leaves significantly increase exposed tree surface area to absorb carbon dioxide (like ions) from the environments (like electrolyte) for photosynthesis, we report a design of micro-conduits in a bioinspired leaves-on-branchlet structure consisting of carbon nanotube arrays serving as branchlets and graphene petals as leaves for such electrodes. The hierarchical all-carbon micro-conduit electrodes with hollow channels exhibit high areal capacitance of 2.35 F cm−2 (~500 F g−1 based on active material mass), high rate capability and outstanding cyclic stability (capacitance retention of ~95% over 10,000 cycles). Furthermore, Nernst–Planck–Poisson calculations elucidate the underlying mechanism of charge transfer and storage governed by sharp graphene petal edges, and thus provides insights into their outstanding electrochemical performance.
Direct observation of single-molecule hydrogen-bond dynamics with single-bond resolution
Authors: Zhou Ce , Li Xingxing , Gong Zhongliang , Jia Chuancheng , Lin Yuanwei , Gu Chunhui , He Gen , Zhong Yuwu , Yang Jinlong , Guo Xuefeng
Published: February 2018

The hydrogen bond represents a fundamental interaction widely existing in nature, which plays a key role in chemical, physical and biochemical processes. However, hydrogen bond dynamics at the molecular level are extremely difficult to directly investigate. Here, in this work we address direct electrical measurements of hydrogen bond dynamics at the single-molecule and single-event level on the basis of the platform of molecular nanocircuits, where a quadrupolar hydrogen bonding system is covalently incorporated into graphene point contacts to build stable supramolecule-assembled single-molecule junctions. The dynamics of individual hydrogen bonds in different solvents at different temperatures are studied in combination with density functional theory. Both experimental and theoretical results consistently show a multimodal distribution, stemming from the stochastic rearrangement of the hydrogen bond structure mainly through intermolecular proton transfer and lactam–lactim tautomerism. This work demonstrates an approach of probing hydrogen bond dynamics with single-bond resolution, making an important contribution to broad fields beyond supramolecular chemistry.
Vps3 and Vps8 control integrin trafficking from early to recycling endosomes and regulate integrin-dependent functions
Authors: Jonker Caspar T. H. , Galmes Romain , Veenendaal Tineke , ten Brink Corlinda , van der Welle Reini E. N. , Liv Nalan , de Rooij Johan , Peden Andrew A. , van der Sluijs Peter , Margadant Coert , Klumperman Judith
Published: February 2018

Recycling endosomes maintain plasma membrane homeostasis and are important for cell polarity, migration, and cytokinesis. Yet, the molecular machineries that drive endocytic recycling remain largely unclear. The CORVET complex is a multi-subunit tether required for fusion between early endosomes. Here we show that the CORVET-specific subunits Vps3 and Vps8 also regulate vesicular transport from early to recycling endosomes. Vps3 and Vps8 localise to Rab4-positive recycling vesicles and co-localise with the CHEVI complex on Rab11-positive recycling endosomes. Depletion of Vps3 or Vps8 does not affect transferrin recycling, but delays the delivery of internalised integrins to recycling endosomes and their subsequent return to the plasma membrane. Consequently, Vps3/8 depletion results in defects in integrin-dependent cell adhesion and spreading, focal adhesion formation, and cell migration. These data reveal a role for Vps3 and Vps8 in a specialised recycling pathway important for integrin trafficking.
Diverse genetic error modes constrain large-scale bio-based production
Authors: Rugbjerg Peter , Myling-Petersen Nils , Porse Andreas , Sarup-Lytzen Kira , Sommer Morten O. A.
Published: February 2018

A transition toward sustainable bio-based chemical production is important for green growth. However, productivity and yield frequently decrease as large-scale microbial fermentation progresses, commonly ascribed to phenotypic variation. Yet, given the high metabolic burden and toxicities, evolutionary processes may also constrain bio-based production. We experimentally simulate large-scale fermentation with mevalonic acid-producing Escherichia coli. By tracking growth rate and production, we uncover how populations fully sacrifice production to gain fitness within 70 generations. Using ultra-deep (>1000×) time-lapse sequencing of the pathway populations, we identify multiple recurring intra-pathway genetic error modes. This genetic heterogeneity is only detected using deep-sequencing and new population-level bioinformatics, suggesting that the problem is underestimated. A quantitative model explains the population dynamics based on enrichment of spontaneous mutant cells. We validate our model by tuning production load and escape rate of the production host and apply multiple orthogonal strategies for postponing genetically driven production declines.
Cobalt-catalyzed electrooxidative C-H/N-H [4+2] annulation with ethylene or ethyne
Authors: Tang Shan , Wang Dan , Liu Yichang , Zeng Li , Lei Aiwen
Published: February 2018

Ethylene and ethyne are among the simplest two-carbon building blocks. However, quite limited methods can be applied to incorporate ethylene or ethyne into fine chemicals. Here we demonstrate a cobalt-catalyzed dehydrogenative C–H/N–H [4+2] annulation of aryl/vinyl amides with ethylene or ethyne by using an electrochemical reaction protocol. Significantly, this work shows an example of electrochemical recycling of cobalt catalyst in oxidative C–H functionalization reactions, avoiding the use of external chemical oxidants and co-oxidants. The electrochemical method provides a reliable and safe way for incorporating gas-phase ethylene or ethyne into fine chemicals. High reaction efficiency and good functional group tolerance are observed under divided electrolytic conditions.
HMG-CoA reductase from Camphor Tulsi (Ocimum kilimandscharicum) regulated MVA dependent biosynthesis of diverse terpenoids in homologous and heterologous plant systems
Authors: Bansal Shilpi , Narnoliya Lokesh Kumar , Mishra Bhawana , Chandra Muktesh , Yadav Ritesh Kumar , Sangwan Neelam Singh
Published: February 2018

Ocimum kilimandscharicum is unique in possessing terpenoids whereas other Ocimum species are renowned for phenylpropanoids as major constituents of essential oil. The key enzyme of MVA/terpenoid metabolic pathway viz 3-hydroxy-3-methylglutaryl Co-A reductase (OkHMGR) of 1.7-Kb ORF encoding ~60-kDa protein was cloned from O. kilimandscharicum and its kinetic characteristics revealed the availability of HMG-CoA as a control point of MVA-pathway. Transcript profiling of the OkHMGR elucidated tissue-specific functions of the gene in flower and leaf tissues in accumulation of terpenoidal essential oil. OkHMGR was differentially regulated in response to exposure to methyl-jasmonate, salicylic-acid, and stress conditions such-as salt and temperature stress, demonstrating its key role in managing signaling and stress-responses. To elucidate its functional role, OkHMGR was transiently over-expressed in homologous and heterologous plants such as O. sanctum, O. basilicum, O. gratissimum, Withania somnifera and Artemisia annua. The over-expression and inhibition dual strategy revealed that the additional OkHMGR in-planta could afford endogenous flow of isoprenoid units towards synthesis of terpenoids. The present study provides in-depth insight of OkHMGR in regulation of biosynthesis of non-plastidal isoprenoids. This is first report on any gene of MVA/isoprenoid pathway from under-explored Camphor Tulsi belonging to genus Ocimum. Studies also suggested that OkHMGR could be a potential tool for attempting metabolic engineering for enhancing medicinally important terpenoidal metabolites in plants.
STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles
Authors: Alshekaili Jalila , Chand Rochna , Lee Cindy Eunhee , Corley Susan , Kwong Kristy , Papa Ilenia , Fulcher David A. , Randall Katrina L. , Leiding Jennifer W. , Ma Cindy S. , Wilkins Marc R. , Uzel Gulbu , Goodnow Chris C. , Vinuesa Carola G. , Tangye Stuart G. , Cook Matthew C.
Published: February 2018

A subset of human follicular helper T cells (TFH) cells expresses CD57 for which no distinct function has been identified. We show that CD57+ TFH cells are universally PD-1hi, but compared to their CD57− PD-1hicounterparts, express little IL-21 or IL-10 among others. Instead, CD57 expression on TFH cells marks cytotoxicity transcriptional signatures that translate into only a weak cytotoxic phenotype. Similarly, circulating PD-1+ CD57+ CD4+ T cells make less cytokine than their CD57− PD-1+ counterparts, but have a prominent cytotoxic phenotype. By analysis of responses to STAT3-dependent cytokines and cells from patients with gain- or loss-of-functionSTAT3mutations, we show that CD4+ T cell cytotoxicity is STAT3-dependent. TFH formation also requires STAT3, but paradoxically, once formed, PD-1hicells become unresponsive to STAT3. These findings suggest that changes in blood and germinal center cytotoxicity might be affected by changes in STAT3 signaling, or modulation of PD-1 by therapy.
Validity of Weyl fermion picture for transition metals monopnictides TaAs, TaP, NbAs, and NbP from ab initio studies
Authors: Grassano Davide , Pulci Olivia , Mosca Conte Adriano , Bechstedt Friedhelm
Published: February 2018

We investigate electronic and optical properties of the topological Weyl semimetals TaAs, TaP, NbAs and NbP crystallizing in bct geometry by means of theab initiodensity functional theory with spin-orbit interaction within the independent-particle approximation. The small energetical overlap of Ta5dor Nb4dderived conduction and valence bands leads to electron and/or hole pockets near the Fermi energy at the 24 Weyl nodes. The nodes give rise to two-(three-)dimensional Dirac cones for theW1(W2) Weyl type. The band dispersion and occupation near the Weyl nodes determine the infrared optical properties. They are dominated by interband transitions, which lead to a deviation from the expected constant values of the imaginary part of the dielectric function. The resulting polarization anisotropy is also visible in the real part of the optical conductivity, whose lineshape deviates from the expected linearity. The details of the Weyl nodes are discussed in relation to recent ARPES results for TaAs and NbP, and compared with measured optical spectra for TaAs. The spectral features of the anisotropic and tilted Weyl fermions are restricted to low excitation energies above absorption onsets due to the band occupation.
A genetic variant in SLC30A2 causes breast dysfunction during lactation by inducing ER stress, oxidative stress and epithelial barrier defects
Authors: Lee Sooyeon , Zhou Yandong , Gill Donald L. , Kelleher Shannon L.
Published: February 2018

SLC30A2 encodes a zinc (Zn) transporter (ZnT2) that imports Zn into vesicles in highly-specialized secretory cells. Numerous mutations and non-synonymous variants in ZnT2 have been reported in humans and in breastfeeding women; ZnT2 variants are associated with abnormally low milk Zn levels and can lead to severe infantile Zn deficiency. However, ZnT2-null mice have profound defects in mammary epithelial cell (MEC) polarity and vesicle secretion, indicating that normal ZnT2 function is critical for MEC function. Here we report that women who harbor a common ZnT2 variant (T288S) present with elevated levels of several oxidative and endoplasmic reticulum (ER) stress markers in their breast milk. Functional studies in vitro suggest that substitution of threonine for serine at amino acid 288 leads to hyperphosphorylation retaining ZnT2 in the ER and lysosomes, increasing ER and lysosomal Zn accumulation, ER stress, the generation of reactive oxygen species, and STAT3 activation. These changes were associated with decreased abundance of zona occludens-1 and increased tight junction permeability. This study confirms that ZnT2 is important for normal breast function in women during lactation, and suggests that women who harbor defective variants in ZnT2 may be at-risk for poor lactation performance.
Low-level Gestational Lead Exposure Alters Dendritic Spine Plasticity in the Hippocampus and Reduces Learning and Memory in Rats
Authors: Zhao Zai-Hua , Zheng Gang , Wang Tao , Du Ke-jun , Han Xiao , Luo Wen-Jing , Shen Xue-Feng , Chen Jing-Yuan
Published: February 2018

Lead (Pb) is known to impair children’s cognitive function. It has been previously shown that developmental Pb exposure alters dendritic spine formation in hippocampal pyramidal neurons. However, the underlying mechanism has not yet been defined. In this study, a low-level gestational Pb exposure (GLE) rat model was employed to investigate the impact of Pb on the spine density of the hippocampal pyramidal neurons and its regulatory mechanism. Pb exposure resulted in impaired performance of the rats in the Morris water maze tasks, and in decreased EPSC amplitudes in hippocampal CA3-CA1 regions. With a 3D reconstruction by the Imaris software, the results from Golgi staining showed that the spine density in the CA1 region was reduced in the Pb-exposed rats in a dose-dependent manner. Decreased spine density was also observed in cultured hippocampal neurons following the Pb treatment. Furthermore, the expression level of NLGN1, a postsynaptic protein that mediates synaptogenesis, was significantly decreased following the Pb exposure bothin vivoandin vitro. Up-regulation of NLGN1 in cultured primary neurons partially attenuated the impact of Pb on the spine density. Taken together, our resultssuggest that Pb exposure alters spine plasticity in the developing hippocampus by down-regulating NLGN1 protein levels.
Functionally distinct smiles elicit different physiological responses in an evaluative context
Authors: Martin Jared D. , Abercrombie Heather C. , Gilboa-Schechtman Eva , Niedenthal Paula M.
Published: February 2018

When people are being evaluated, their whole body responds. Verbal feedback causes robust activation in the hypothalamic-pituitary-adrenal (HPA) axis. What about nonverbal evaluative feedback? Recent discoveries about the social functions of facial expression have documented three morphologically distinct smiles, which serve the functions of reinforcement, social smoothing, and social challenge. In the present study, participants saw instances of one of three smile types from an evaluator during a modified social stress test. We find evidence in support of the claim that functionally different smiles are sufficient to augment or dampen HPA axis activity. We also find that responses to the meanings of smiles as evaluative feedback are more differentiated in individuals with higher baseline high-frequency heart rate variability (HF-HRV), which is associated with facial expression recognition accuracy. The differentiation is especially evident in response to smiles that are more ambiguous in context. Findings suggest that facial expressions have deep physiological implications and that smiles regulate the social world in a highly nuanced fashion.
Reduced graphene oxide (rGO) based wideband optical sensor and the role of Temperature, Defect States and Quantum Efficiency
Authors: Abid  , Sehrawat Poonam , Islam S. S. , Mishra Prabhash , Ahmad Shahab
Published: February 2018

We report a facile and cost-effective approach to develop self-standing reduced Graphene Oxide (rGO) film based optical sensor and its low-temperature performance analysis where midgap defect states play a key role in tuning the crucial sensor parameters. Graphite oxide (GO) is produced by modified Hummers’ method and reduced thermally at 250 °C for 1 h in Argon atmosphere to obtain rGO. Self-standing rGO film is prepared via vacuum filtration. The developed film is characterized by HRTEM, FESEM, Raman, and XRD techniques. The developed sensor exhibits highest sensitivity towards 635 nm illumination wavelength, irrespective of the operating temperature. For a given excitation wavelength, photoresponse study at low temperature (123K–303K) reveals inverse relationship between sensitivity and operating temperature. Highest sensitivity of 49.2% is obtained at 123 K for 635 nm laser at power density of 1.4 mW/mm2. Unlike sensitivity, response- and recovery-time demonstrate directly proportional dependence with operating temperature. Power dependent studies establish linear relation between power-density and sensitivity, and a safe limit beyond which sample heating prolongs the recovery time. Wavelength-dependent studies shows that proposed sensor can efficiently operate from visible to near NIR region. To the best of our knowledge such rGO based optical sensor performance at low temperature had not been reported earlier.
Sub-cellular In-situ Characterization of Ferritin(iron) in a Rodent Model of Spinal Cord Injury
Authors: Blissett A. R. , Deng B. , Wei P. , Walsh K. J. , Ollander B. , Sifford J. , Sauerbeck A. D. , McComb D. W. , McTigue D. M. , Agarwal G.
Published: February 2018

Iron (Fe) is an essential metal involved in a wide spectrum of physiological functions. Sub-cellular characterization of the size, composition, and distribution of ferritin(iron) can provide valuable information on iron storage and transport in health and disease. In this study we employ magnetic force microscopy (MFM), transmission electron microscopy (TEM), and electron energy loss spectroscopy (EELS) to characterize differences in ferritin(iron) distribution and composition across injured and non-injured tissues by employing a rodent model of spinal cord injury (SCI). Our biophysical and ultrastructural analyses provide novel insights into iron distribution which are not obtained by routine biochemical stains. In particular, ferritin(iron) rich lysosomes revealed increased heterogeneity in MFM signal from tissues of SCI animals. Ultrastructural analysis using TEM elucidated that both cytosolic and lysosomal ferritin(iron) density was increased in the injured (spinal cord) and non-injured (spleen) tissues of SCI as compared to naïve animals. In-situ EELs analysis revealed that ferritin(iron) was primarily in Fe3+ oxidation state in both naïve and SCI animal tissues. The insights provided by this study and the approaches utilized here can be applied broadly to other systemic problems involving iron regulation or to understand the fate of exogenously delivered iron-oxide nanoparticles.
A combinatorial framework to quantify peak/pit asymmetries in complex dynamics
Authors: Hasson Uri , Iacovacci Jacopo , Davis Ben , Flanagan Ryan , Tagliazucchi Enzo , Laufs Helmut , Lacasa Lucas
Published: February 2018

We explore a combinatorial framework which efficiently quantifies the asymmetries between minima and maxima in local fluctuations of time series. We first showcase its performance by applying it to a battery of synthetic cases. We find rigorous results on some canonical dynamical models (stochastic processes with and without correlations, chaotic processes) complemented by extensive numerical simulations for a range of processes which indicate that the methodology correctly distinguishes different complex dynamics and outperforms state of the art metrics in several cases. Subsequently, we apply this methodology to real-world problems emerging across several disciplines including cases in neurobiology, finance and climate science. We conclude that differences between the statistics of local maxima and local minima in time series are highly informative of the complex underlying dynamics and a graph-theoretic extraction procedure allows to use these features for statistical learning purposes.
Comparative transcriptomics of multidrug-resistant Acinetobacter baumannii in response to antibiotic treatments
Authors: Qin Hao , Lo Norman Wai-Sing , Loo Jacky , Lin Xiao , Yim Aldrin Kay-Yuen , Tsui Stephen Kwok-Wing , Lau Terrence Chi-Kong , Ip Margaret , Chan Ting-Fung
Published: February 2018

Multidrug-resistant Acinetobacter baumannii, a major hospital-acquired pathogen, is a serious health threat and poses a great challenge to healthcare providers. Although there have been many genomic studies on the evolution and antibiotic resistance of this species, there have been very limited transcriptome studies on its responses to antibiotics. We conducted a comparative transcriptomic study on 12 strains with different growth rates and antibiotic resistance profiles, including 3 fast-growing pan-drug-resistant strains, under separate treatment with 3 antibiotics, namely amikacin, imipenem, and meropenem. We performed deep sequencing using a strand-specific RNA-sequencing protocol, and used de novo transcriptome assembly to analyze gene expression in the form of polycistronic transcripts. Our results indicated that genes associated with transposable elements generally showed higher levels of expression under antibiotic-treated conditions, and many of these transposon-associated genes have previously been linked to drug resistance. Using co-expressed transposon genes as markers, we further identified and experimentally validated two novel genes of which overexpression conferred significant increases in amikacin resistance. To the best of our knowledge, this study represents the first comparative transcriptomic analysis of multidrug-resistant A. baumannii under different antibiotic treatments, and revealed a new relationship between transposons and antibiotic resistance.
Indian Summer Monsoon Simulations: Usefulness of Increasing Horizontal Resolution, Manual Tuning, and Semi-Automatic Tuning in Reducing Present-Day Model Biases
Authors: Anand Abhishek , Mishra Saroj K. , Sahany Sandeep , Bhowmick Mansi , Rawat Janmejai Singh , Dash S. K.
Published: February 2018

Coupled Global Climate Models (CGCMs) of the Coupled Model Intercomparison Project Phase 5 (CMIP5) are unable to resolve the spatial and temporal characteristics of the South Asian Monsoon satisfactorily. A CGCM with the capability to reliably project the global as well as the regional climatic features would be a valuable tool for scientists and policymakers. Analysis of 28 CMIP5 models highlights varying degree of biases in precipitation and 2 m surface air temperature (T2m) over south Asia, and the Community Earth System Model (CESM) developed at the National Center for Atmospheric Research is found to be one of the best performing models. However, like all other CMIP5 models, CESM also has some inherent model biases. Using CESM, it is found that the precipitation and T2M biases reduce with increase in the model horizontal resolution from 2° to 0.5°. Further, a few deep convective parameters in the Zhang-McFarlane convection scheme are tuned for 2° and 1° model resolutions using both manual and semi-automatic model tuning methods. Comparing results from the two tuning methods we find that the performance of the manually tuned model is better than that of the semi-automated one.
Profiling Atlantic salmon B cell populations: CpG-mediated TLR-ligation enhances IgM secretion and modulates immune gene expression
Authors: Jenberie Shiferaw , Thim Hanna L. , Sunyer J. Oriol , Skjødt Karsten , Jensen Ingvill , Jørgensen Jorunn B.
Published: February 2018

While TLR-activated pathways are key regulators of B cell responses in mammals, their impact on teleost B cells are scarcely addressed. Here, the potential of Atlantic salmon B cells to respond to TLR ligands was shown by demonstrating a constitutive expression of nucleic-acid sensing TLRs in magnetic sorted IgM+ cells. Of the two receptors recognizing CpG in teleosts, tlr9 was the dominating receptor with over ten-fold higher expression than tlr21. Upon CpG-stimulation, IgM secretion increased for head kidney (HK) and splenic IgM+ cells, while blood B cells were marginally affected. The results suggest that CpG directly affects salmon B cells to differentiate into antibody secreting cells (ASCs). IgM secretion was also detected in the non-treated controls, again with the highest levels in the HK derived population, signifying that persisting ASCs are present in this tissue. In all tissues, the IgM+ cells expressed high MHCII levels, suggesting antigen-presenting functions. Upon CpG-treatment the co-stimulatory molecules cd83 and cd40 were upregulated, while cd86 was down-regulated under the same conditions. Finally, ifna1 was upregulated upon CpG-stimulation in all tissues, while a restricted upregulation was evident for ifnb, proposing that salmon IgM+ B cells exhibit a type I IFN-response.
Wrinkled Nitrogen-doped Carbon Belts
Authors: Fajardo-Díaz Juan L. , López-Urías Florentino , Muñoz-Sandoval Emilio
Published: February 2018

Graphene, carbon nanotubes, and fullerenes are nanomaterials with outstanding properties such as electrical, thermal, mechanical strength, flexibility, and high surface area. These nanomaterials are used as building blocks for the construction of novel and astonishing 3D-dimensional networks. In the present work, nitrogen-doped carbon belt (N-CB) structures containing wrinkled carbon fibres as building blocks were synthesized under unstable conditions in a chemical vapour deposition experiment. N-CB structures with 0.2–3.0 microns of wide and 350 nm thick were assembled from complex individual wrinkled carbon fibres grown on Co/Cu films. These complex structures have a tubular appearance, showing holed and wrinkled graphite layers. Sulphur and copper atoms drastically affect the catalytic role of cobalt, changing the conventional growth of carbon nanotubes. Chemical functional groups, N-doping, and carbons hybridizations involved in the winkled carbon fibres are investigated. These findings provides a novel material that can be used as an excellent oxygen-reduction reaction catalyst or nano-electronics component.
Lung Metabolism and Inflammation during Mechanical Ventilation; An Imaging Approach
Authors: Pourfathi Mehrdad , Cereda Maurizio , Chatterjee Shampa , Xin Yi , Kadlecek Stephen , Duncan Ian , Hamedani Hooman , Siddiqui Sarmad , Profka Harrilla , Ehrich Jason , Ruppert Kai , Rizi Rahim R.
Published: February 2018

Acute respiratory distress syndrome (ARDS) is a major cause of mortality in critically ill patients. Patients are currently managed by protective ventilation and alveolar recruitment using positive-end expiratory pressure (PEEP). However, the PEEP’s effect on both pulmonary metabolism and regional inflammation is poorly understood. Here, we demonstrate the effect of PEEP on pulmonary anaerobic metabolism in mechanically ventilated injured rats, using hyperpolarized carbon-13 imaging. Pulmonary lactate-to-pyruvate ratio was measured in 21 rats; 14 rats received intratracheal instillation of hydrochloric-acid, while 7 rats received sham saline. 1 hour after acid/saline instillation, PEEP was lowered to 0 cmH2O in 7 injured rats (ZEEP group) and in all sham rats; PEEP was continued in the remaining 7 injured rats (PEEP group). Pulmonary compliance, oxygen saturation, histological injury scores, ICAM-1 expression and myeloperoxidase expression were measured. Lactate-to-pyruvate ratio progressively increased in the dependent lung during mechanical ventilation at ZEEP (p < 0.001), but remained unchanged in PEEP and sham rats. Lactate-to-pyruvate ratio was correlated with hyaline membrane deposition (r = 0.612), edema severity (r = 0.663), ICAM-1 (r = 0.782) and myeloperoxidase expressions (r = 0.817). Anaerobic pulmonary metabolism increases during lung injury progression and is contained by PEEP. Pulmonary lactate-to-pyruvate ratio may indicate in-vivo neutrophil activity due to atelectasis.
Scalable Culturing of Primary Human Glioblastoma Tumor-Initiating Cells with a Cell-Friendly Culture System
Authors: Li Qiang , Lin Haishuang , Rauch Jack , Deleyrolle Loic P. , Reynolds Brent A. , Viljoen Hendrik J. , Zhang Chi , Zhang Chi , Gu Linxia , Van Wyk Erika , Lei Yuguo
Published: February 2018

Glioblastoma is the most aggressive and deadly brain cancer. There is growing interest to develop drugs that specifically target to glioblastoma tumor-initiating cells (TICs). However, the cost-effective production of large numbers of high quality glioblastoma TICs for drug discovery with current cell culturing technologies remains very challenging. Here, we report a new method that cultures glioblastoma TICs in microscale alginate hydrogel tubes (or AlgTubes). The AlgTubes allowed long-term culturing (~50 days, 10 passages) of glioblastoma TICs with high growth rate (~700-fold expansion/14 days), high cell viability and high volumetric yield (~3.0 × 108 cells/mL) without losing the stem cell properties, all offered large advancements over current culturing methods. This method can be applied for the scalable production of glioblastoma TICs at affordable cost for drug discovery.
Diversification of insects since the Devonian: a new approach based on morphological disparity of mouthparts
Authors: Nel Patricia , Bertrand Sylvain , Nel André
Published: February 2018

The majority of the analyses of the evolutionary history of the megadiverse class Insecta are based on the documented taxonomic palaeobiodiversity. A different approach, poorly investigated, is to focus on morphological disparity, linked to changes in the organisms’ functioning. Here we establish a hierarchy of the great geological epochs based on a new method using Wagner parsimony and a ‘presence/absence of a morphological type of mouthpart of Hexapoda’ dataset. We showed the absence of major rupture in the evolution of the mouthparts, but six epochs during which numerous innovations and few extinctions happened, i.e., Late Carboniferous, Middle and Late Triassic, ‘Callovian-Oxfordian’, ‘Early’ Cretaceous, and ‘Albian-Cenomanian’. The three crises Permian-Triassic, Triassic-Jurassic, and Cretaceous-Cenozoic had no strong, visible impact on mouthparts types. We particularly emphasize the origination of mouthparts linked to nectarivory during the Cretaceous Terrestrial Revolution. We also underline the origination of mouthparts linked to phytophagy during the Middle and the Late Triassic, correlated to the diversification of the gymnosperms, especially in relation to the complex ‘flowers’ producing nectar of the Bennettitales and Gnetales.
BI-2536 and BI-6727, dual Polo-like kinase/bromodomain inhibitors, effectively reactivate latent HIV-1
Authors: Gohda Jin , Suzuki Kazuo , Liu Kai , Xie Xialin , Takeuchi Hiroaki , Inoue Jun-ichiro , Kawaguchi Yasushi , Ishida Takaomi
Published: February 2018

HIV-1 latent reservoirs harbouring silenced but replication-competent proviruses are a major obstacle against viral eradication in infected patients. The “shock and kill” strategy aims to reactivate latent provirus with latency reversing agents (LRAs) in the presence of antiretroviral drugs, necessitating the development of effective and efficient LRAs. We screened a chemical library for potential LRAs and identified two dual Polo-like kinase (PLK)/bromodomain inhibitors, BI-2536 and BI-6727 (volasertib), which are currently undergoing clinical trials against various cancers. BI-2536 and BI-6727 significantly reactivated silenced HIV-1 provirus at both the mRNA and protein level in two latently infected model cell lines (ACH2 and U1). BI-2536 dramatically reactivated transcription of latent HIV-1 provirus in peripheral blood mononuclear cells derived from infected patients. Long terminal repeat activation by the inhibitors was associated with bromodomain rather than PLK inhibition. We also found that BI-2536 synergistically activates the latent provirus in combination with SAHA, a histone deacetylase inhibitor, or the non-tumour-promoting phorbol ester prostratin. Our findings strongly suggest that BI-2536 and BI-6727 are potent LRAs for the “shock and kill” HIV-1 eradication strategy.
An all-trans-retinal-binding opsin peropsin as a potential dark-active and light-inactivated G protein-coupled receptor
Authors: Nagata Takashi , Koyanagi Mitsumasa , Lucas Robert , Terakita Akihisa
Published: February 2018

Peropsin or retinal pigment epithelium-derived rhodopsin homolog, found in many animals, belongs to the opsin family. Most opsins bind to 11-cis-retinal as a chromophore and act as light-activated G protein-coupled receptors. Some peropsins, however, bind all-trans-retinal and isomerise it into 11-cis form by light, and peropsin has been suggested to supply other visual opsins with 11-cis-retinal. Additionally, peropsin has some amino acid sequence motifs that are highly conserved among G protein-coupled opsins. Here, using chimeric mutant peropsins, we found that peropsin potentially generates an “active form” that drives G-protein signalling in the dark by binding to all-trans-retinal and that the active form photo-converts to an inactive form containing 11-cis-retinal. Comparative spectroscopic analysis demonstrated that spider peropsin exhibited catalytic efficiency for retinal photoisomerisation that was much lower than a retinal photoisomerase, squid retinochrome. The chimeric peropsins, constructed by replacing the third intracellular loop region with that of Gs- or Gi-coupled opsin, were active and drove Gs- or Gi-mediated signalling in the dark, respectively, and were inactivated upon illumination in mammalian cultured cells. These results suggest that peropsin acts as a dark-active, light-inactivated G protein-coupled receptor and is useful as a novel optogenetic tool.