bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of XIAP facilitates switch to TNFα-induced necroptosis in mouse neutrophils
Authors: Wicki Simone , Gurzeler Ursina , Wei-Lynn Wong W , Jost Philipp J , Bachmann Daniel , Kaufmann Thomas
Published: October 2016

Neutrophils are essential players in the first-line defense against invading bacteria and fungi. Besides its antiapoptotic role, the inhibitor of apoptosis protein (IAP) family member X-linked IAP (XIAP) has been shown to regulate innate immune signaling. Whereas the role of XIAP in innate signaling pathways is derived mostly from work in macrophages and dendritic cells, it is not known if and how XIAP contributes to these pathways in neutrophils. Here we show that in response to bacterial lipopolysaccharides (LPS), mouse neutrophils secreted considerable amounts of tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) and, in accordance with earlier reports, XIAP prevented LPS-induced hypersecretion of IL-1β also in neutrophils. Interestingly, and in contrast to macrophages or dendritic cells, Xiap-deficient neutrophils were insensitive to LPS-induced cell death. However, combined loss of function of XIAP and cIAP1/-2 resulted in rapid neutrophil cell death in response to LPS. This cell death occurred by classical apoptosis initiated by a TNFα- and RIPK1-dependent, but RIPK3- and MLKL-independent, pathway. Inhibition of caspases under the same experimental conditions caused a shift to RIPK3-dependent cell death. Accordingly, we demonstrate that treatment of neutrophils with high concentrations of TNFα induced apoptotic cell death, which was fully blockable by pancaspase inhibition in wild-type neutrophils. However, in the absence of XIAP, caspase inhibition resulted in a shift from apoptosis to RIPK3- and MLKL-dependent necroptosis. Loss of XIAP further sensitized granulocyte–macrophage colony-stimulating factor (GM-CSF)-primed neutrophils to TNFα-induced killing. These data suggest that XIAP antagonizes the switch from TNFα-induced apoptosis to necroptosis in mouse neutrophils. Moreover, our data may implicate an important role of neutrophils in the development of hyperinflammation and disease progression of patients diagnosed with X-linked lymphoproliferative syndrome type 2, which are deficient in XIAP.
Transactivation of TrkB by Sigma-1 receptor mediates cocaine-induced changes in dendritic spine density and morphology in hippocampal and cortical neurons
Authors: Ka Minhan , Kook Yeon-Hee , Liao Ke , Buch Shilpa , Kim Woo-Yang
Published: October 2016

Cocaine is a highly addictive narcotic associated with dendritic spine plasticity in the striatum. However, it remains elusive whether cocaine modifies spines in a cell type-specific or region-specific manner or whether it alters different types of synapses in the brain. In addition, there is a paucity of data on the regulatory mechanism(s) involved in cocaine-induced modification of spine density. In the current study, we report that cocaine exposure differentially alters spine density, spine morphology, and the types of synapses in hippocampal and cortical neurons. Cocaine exposure in the hippocampus resulted in increased spine density, but had no significant effect on cortical neurons. Although cocaine exposure altered spine morphology in both cell types, the patterns of spine morphology were distinct for each cell type. Furthermore, we observed that cocaine selectively affects the density of excitatory synapses. Intriguingly, in hippocampal neurons cocaine-mediated effects on spine density and morphology involved sigma-1 receptor (Sig-1 R) and its downstream TrkB signaling, which were not the case in cortical neurons. Furthermore, pharmacological inhibition of Sig-1 R prevented cocaine-induced TrkB activation in hippocampal neurons. Our findings reveal a novel mechanism by which cocaine induces selective changes in spine morphology, spine density, and synapse formation, and could provide insights into the cellular basis for the cognitive impairment observed in cocaine addicts.
Increased oxidative phosphorylation in response to acute and chronic DNA damage
Authors: Brace Lear E , Vose Sarah C , Stanya Kristopher , Gathungu Rose M , Marur Vasant R , Longchamp Alban , Treviño-Villarreal Humberto , Mejia Pedro , Vargas Dorathy , Inouye Karen , Bronson Roderick T , Lee Chih-Hao , Neilan Edward , Kristal Bruce S , Mitchell James R
Published: October 2016

Accumulation of DNA damage is intricately linked to aging, aging-related diseases and progeroid syndromes such as Cockayne syndrome (CS). Free radicals from endogenous oxidative energy metabolism can damage DNA, however the potential of acute or chronic DNA damage to modulate cellular and/or organismal energy metabolism remains largely unexplored. We modeled chronic endogenous genotoxic stress using a DNA repair-deficient Csa−/−|Xpa−/− mouse model of CS. Exogenous genotoxic stress was modeled in mice in vivo and primary cells in vitro treated with different genotoxins giving rise to diverse spectrums of lesions, including ultraviolet radiation, intrastrand crosslinking agents and ionizing radiation. Both chronic endogenous and acute exogenous genotoxic stress increased mitochondrial fatty acid oxidation (FAO) on the organismal level, manifested by increased oxygen consumption, reduced respiratory exchange ratio, progressive adipose loss and increased FAO in tissues ex vivo. In multiple primary cell types, the metabolic response to different genotoxins manifested as a cell-autonomous increase in oxidative phosphorylation (OXPHOS) subsequent to a transient decline in steady-state NAD+ and ATP levels, and required the DNA damage sensor PARP-1 and energy-sensing kinase AMPK. We conclude that increased FAO/OXPHOS is a general, beneficial, adaptive response to DNA damage on cellular and organismal levels, illustrating a fundamental link between genotoxic stress and energy metabolism driven by the energetic cost of DNA damage. Our study points to therapeutic opportunities to mitigate detrimental effects of DNA damage on primary cells in the context of radio/chemotherapy or progeroid syndromes.
Inappropriate asthma therapy—a tale of two countries: a parallel population-based cohort study
Authors: Belhassen Manon , Nibber Anjan , Van Ganse Eric , Ryan Dermot , Langlois Carole , Appiagyei Francis , Skinner Derek , Laforest Laurent , Soriano Joan B , Price David
Published: October 2016

Against recurrent controversies around the safety of short- and long-acting β2-agonists (SABA and LABA), and the National Review of Asthma Deaths inquiry in the United Kingdom, we investigated the prevalence of inappropriate therapy in asthma. Our study aimed to determine the prevalence of inappropriate use of asthma therapy in the United Kingdom and in France. Two interval, parallel, population-based cohorts (2007 and 2013) were developed in each country by using the UK OPCRD and the French EGB databases. Patients aged 6–40 years were studied over the 12-month period following inclusion, regarding overuse (⩾12 units) of SABA, use of LABA without inhaled corticosteroids (ICS) and ⩾2-fold higher use of LABA compared with that of ICS. Overall, 39,743 UK and 4,910 French patients were included in 2007, and 14,036 and 5,657 patients, respectively, were included in 2013. UK adults were more frequently exposed to SABA overuse compared with those in France in both periods, with an upward trend in the United Kingdom (P<0.05). In 2013, LABA use without ICS occurred in 0.1% and 1.5% of United Kingdom and French adults, respectively. Unbalanced use of LABA relative to ICS became marginal in both countries in 2013. Inappropriate use of therapy was less marked, but present, in children. Inappropriate therapy remains a common issue in asthma. Based on our figures, it may be estimated that >210,000 British and >190,000 French asthmatics aged 6–40 years were inappropriately treated in 2013.
Correction: Corrigendum: TNFR2 expression by CD4 effector T cells is required to induce full-fledged experimental colitis
Authors: Chen Xin , Nie Yingjie , Xiao Haitao , Bian Zhaoxiang , Scarzello Anthony J. , Song Na-Young , Trivett Anna L. , Yang De , Oppenheim Joost J.
Published: October 2016

Scientific Reports 6: Article number: 32834; published online: 07 September 2016; updated: 13 October 2016
Soybean-derived Bowman-Birk Inhibitor (BBI) Inhibits HIV Replication in Macrophages
Authors: Ma Tong-Cui , Zhou Run-Hong , Wang Xu , Li Jie-Liang , Sang Ming , Zhou Li , Zhuang Ke , Hou Wei , Guo De-Yin , Ho Wen-Zhe
Published: October 2016

The Bowman-Birk inhibitor (BBI), a soybean-derived protease inhibitor, is known to have anti-inflammatory effect in both in vitro and in vivo systems. Macrophages play a key role in inflammation and immune activation, which is implicated in HIV disease progression. Here, we investigated the effect of BBI on HIV infection of peripheral blood monocyte-derived macrophages. We demonstrated that BBI could potently inhibit HIV replication in macrophages without cytotoxicity. Investigation of the mechanism(s) of BBI action on HIV showed that BBI induced the expression of IFN-β and multiple IFN stimulated genes (ISGs), including Myxovirus resistance protein 2 (Mx2), 2′,5′-oligoadenylate synthetase (OAS-1), Virus inhibitory protein (viperin), ISG15 and ISG56. BBI treatment of macrophages also increased the expression of several known HIV restriction factors, including APOBEC3F, APOBEC3G and tetherin. Furthermore, BBI enhanced the phosphorylation of IRF3, a key regulator of IFN-β. The inhibition of IFN-β pathway by the neutralization antibody to type I IFN receptor (Anti-IFNAR) abolished BBI-mediated induction of the anti-HIV factors and inhibition of HIV in macrophages. These findings that BBI could activate IFN-β-mediated signaling pathway, initialize the intracellular innate immunity in macrophages and potently inhibit HIV at multiple steps of viral replication cycle indicate the necessity to further investigate BBI as an alternative and cost-effective anti-HIV natural product.
Pressure induced elastic softening in framework aluminosilicate- albite (NaAlSi3O8)
Authors: Mookherjee Mainak , Mainprice David , Maheshwari Ketan , Heinonen Olle , Patel Dhenu , Hariharan Anant
Published: October 2016

Albite (NaAlSi3O8) is an aluminosilicate mineral. Its crystal structure consists of 3-D framework of Al and Si tetrahedral units. We have used Density Functional Theory to investigate the high-pressure behavior of the crystal structure and how it affects the elasticity of albite. Our results indicate elastic softening between 6–8 GPa. This is observed in all the individual elastic stiffness components. Our analysis indicates that the softening is due to the response of the three-dimensional tetrahedral framework, in particular by the pressure dependent changes in the tetrahedral tilts. At pressure <6 GPa, the PAW-GGA can be described by a Birch-Murnaghan equation of state with "Equation missing" = 687.4 Å3, "Equation missing" = 51.7 GPa, and "Equation missing" = 4.7. The shear modulus and its pressure derivative are "Equation missing" = 33.7 GPa, and "Equation missing" = 2.9. At 1 bar, the azimuthal compressional and shear wave anisotropy "Equation missing" = 42.8%, and "Equation missing" = 50.1%. We also investigate the densification of albite to a mixture of jadeite and quartz. The transformation is likely to cause a discontinuity in density, compressional, and shear wave velocity across the crust and mantle. This could partially account for the Mohorovicic discontinuity in thickened continental crustal regions.
Entropic and Near-Field Improvements of Thermoradiative Cells
Authors: Hsu Wei-Chun , Tong Jonathan K. , Liao Bolin , Huang Yi , Boriskina Svetlana V. , Chen Gang
Published: October 2016

A p-n junction maintained at above ambient temperature can work as a heat engine, converting some of the supplied heat into electricity and rejecting entropy by interband emission. Such thermoradiative cells have potential to harvest low-grade heat into electricity. By analyzing the entropy content of different spectral components of thermal radiation, we identify an approach to increase the efficiency of thermoradiative cells via spectrally selecting long-wavelength photons for radiative exchange. Furthermore, we predict that the near-field photon extraction by coupling photons generated from interband electronic transition to phonon polariton modes on the surface of a heat sink can increase the conversion efficiency as well as the power generation density, providing more opportunities to efficiently utilize terrestrial emission for clean energy. An ideal InSb thermoradiative cell can achieve a maximum efficiency and power density up to 20.4% and 327 Wm−2, respectively, between a hot source at 500 K and a cold sink at 300 K. However, sub-bandgap and non-radiative losses will significantly degrade the cell performance.
Predicting Global Minimum in Complex Beryllium Borate System for Deep-ultraviolet Functional Optical Applications
Authors: Bian Qiang , Yang Zhihua , Wang Ying , Cao Chao , Pan Shilie
Published: October 2016

Searching for high performance materials for optical communication and laser industry in deep-ultraviolet (DUV) region has been the subject of considerable interest. Such materials by design from scratching on multi-component complex crystal systems are challenging. Here, we predict, through density function calculations and unbiased structure searching techniques, the formation of quaternary NaBeBO3 compounds at ambient pressure. Among the four low-energy phases, the P63/m structure exhibits a DUV cutoff edge of 20 nm shorter than α-BaB2O4 (189 nm) – the best-known DUV birefringent material. While the P-6 structure exhibits one time second-harmonic generation efficiency of KH2PO4 and possesses excellent crystal growth habit without showing any layer habit as observed in the only available DUV nonlinear optical material KBe2BO3F2, whose layer habit limits its wide industrial applications. These NaBeBO3 structures are promising candidates for the next generation of DUV optical materials, and the structure prediction technique will shed light on future optical materials design.
SOXE neofunctionalization and elaboration of the neural crest during chordate evolution
Authors: Tai Andrew , Cheung Martin , Huang Yong-Heng , Jauch Ralf , Bronner Marianne E. , Cheah Kathryn S. E.
Published: October 2016

During chordate evolution, two genome-wide duplications facilitated acquisition of vertebrate traits, including emergence of neural crest cells (NCCs), in which neofunctionalization of the duplicated genes are thought to have facilitated development of craniofacial structures and the peripheral nervous system. How these duplicated genes evolve and acquire the ability to specify NC and their derivatives are largely unknown. Vertebrate SoxE paralogues, most notably Sox9/10, are essential for NC induction, delamination and lineage specification. In contrast, the basal chordate, amphioxus, has a single SoxE gene and lacks NC-like cells. Here, we test the hypothesis that duplication and divergence of an ancestral SoxE gene may have facilitated elaboration of NC lineages. By using an in vivo expression assay to compare effects of AmphiSoxE and vertebrate Sox9 on NC development, we demonstrate that all SOXE proteins possess similar DNA binding and homodimerization properties and can induce NCCs. However, AmphiSOXE is less efficient than SOX9 in transactivation activity and in the ability to preferentially promote glial over neuronal fate, a difference that lies within the combined properties of amino terminal and transactivation domains. We propose that acquisition of AmphiSoxE expression in the neural plate border led to NCC emergence while duplication and divergence produced advantageous mutations in vertebrate homologues, promoting elaboration of NC traits.
Lipocalin 2 prevents intestinal inflammation by enhancing phagocytic bacterial clearance in macrophages
Authors: Toyonaga Takahiko , Matsuura Minoru , Mori Kiyoshi , Honzawa Yusuke , Minami Naoki , Yamada Satoshi , Kobayashi Taku , Hibi Toshifumi , Nakase Hiroshi
Published: October 2016

Lipocalin 2 (Lcn2), also called neutrophil gelatinase B-associated lipocalin (NGAL), is an anti-microbial peptide originally identified in neutrophil granules. Although Lcn2/NGAL expression is increased in the inflamed intestinal tissues of patients with inflammatory bowel disease, the role of Lcn2/NGAL in the development of intestinal inflammation remains unclear. Here we investigated the role of Lcn2/NGAL in intestinal inflammation using a spontaneous mouse colitis model, interleukin-10 knock out (IL-10 KO) mice. Lcn2 expression in the colonic tissues of IL-10 KO mice increased with the development of colitis. Lcn2/IL-10 double-KO mice showed a more rapid onset and development of colitis compared to IL-10 KO mice. Lcn2 enhanced phagocytic bacterial clearance in macrophages in vitro after infection with Escherichia coli. Transfer of Lcn2-repleted macrophages prevented the development of colitis in Lcn2/IL-10 double-KO mice in vivo. Our findings revealed that Lcn2 prevents the development of intestinal inflammation. One crucial factor seems to be the enhancement of phagocytic bacterial clearance in macrophages by Lcn2.
Cloning and in vitro characterization of a Schistosoma japonicum aquaglyceroporin that functions in osmoregulation
Authors: Huang Yuzheng , Li Wei , Lu Wuguang , Xiong Chunrong , Yang Yang , Yan Huaijiang , Liu Kun Connie , Cao Peng
Published: October 2016

As one of the three major human pathogens that cause schistosomiasis, Schistosoma japonicum is the only one that is endemic in China. Despite great progress on schistosomiasis control over the past 50 years in China, S. japonicum transmission still occurs in certain endemic regions, which causes significant public health problems and enormous economic losses. During different life stages, parasites are able to survive dramatic osmolality changes between its vector, fresh water, and mammal host. However, the molecular mechanism of parasite osmoregulation remains unknown. To address this challenging question, we report the first cloning of an S. japonicum aquaglyceroporin (SjAQP) from an isolate from Jiangsu province, China. Expressing SjAQP in Xenopus oocytes facilitated the permeation of water, glycerol, and urea. The water permeability of SjAQP was inhibited by 1 mM HgCl2, 3 mM tetraethylammonium, 1 mM ZnCl2, and 1 mM CuSO4. SjAQP was constitutively expressed throughout the S. japonicum life cycle, including in the egg, miracidia, cercaria, and adult stages. The highest expression was detected during the infective cercaria stage. Our results suggest that SjAQP plays a role in osmoregulation throughout the S. japonicum life cycle, especially during cercariae transformation, which enables parasites to survive osmotic challenges.
Enhanced Volatile Organic Compounds emissions and organic aerosol mass increase the oligomer content of atmospheric aerosols
Authors: Kourtchev Ivan , Giorio Chiara , Manninen Antti , Wilson Eoin , Mahon Brendan , Aalto Juho , Kajos Maija , Venables Dean , Ruuskanen Taina , Levula Janne , Loponen Matti , Connors Sarah , Harris Neil , Zhao Defeng , Kiendler-Scharr Astrid , Mentel Thomas , Rudich Yinon , Hallquist Mattias , Doussin Jean-Francois , Maenhaut Willy , Bäck Jaana , Petäjä Tuukka , Wenger John , Kulmala Markku , Kalberer Markus
Published: October 2016

Secondary organic aerosol (SOA) accounts for a dominant fraction of the submicron atmospheric particle mass, but knowledge of the formation, composition and climate effects of SOA is incomplete and limits our understanding of overall aerosol effects in the atmosphere. Organic oligomers were discovered as dominant components in SOA over a decade ago in laboratory experiments and have since been proposed to play a dominant role in many aerosol processes. However, it remains unclear whether oligomers are relevant under ambient atmospheric conditions because they are often not clearly observed in field samples. Here we resolve this long-standing discrepancy by showing that elevated SOA mass is one of the key drivers of oligomer formation in the ambient atmosphere and laboratory experiments. We show for the first time that a specific organic compound class in aerosols, oligomers, is strongly correlated with cloud condensation nuclei (CCN) activities of SOA particles. These findings might have important implications for future climate scenarios where increased temperatures cause higher biogenic volatile organic compound (VOC) emissions, which in turn lead to higher SOA mass formation and significant changes in SOA composition. Such processes would need to be considered in climate models for a realistic representation of future aerosol-climate-biosphere feedbacks.
Compact hematite buffer layer as a promoter of nanorod photoanode performances
Authors: Milan R. , Cattarin S. , Comisso N. , Baratto C. , Kaunisto K. , Tkachenko N. V. , Concina I.
Published: October 2016

The effect of a thin α-Fe2O3 compact buffer layer (BL) on the photoelectrochemical performances of a bare α-Fe2O3 nanorods photoanode is investigated. The BL is prepared through a simple spray deposition onto a fluorine-doped tin oxide (FTO) conducting glass substrate before the growth of a α-Fe2O3 nanorods via a hydrothermal process. Insertion of the hematite BL between the FTO and the nanorods markedly enhances the generated photocurrent, by limiting undesired losses of photogenerated charges at the FTO||electrolyte interface. The proposed approach warrants a marked improvement of material performances, with no additional thermal treatment and no use/dispersion of rare or toxic species, in agreement with the principles of green chemistry.
Assembling the Setaria italica L. Beauv. genome into nine chromosomes and insights into regions affecting growth and drought tolerance
Authors: Tsai Kevin J. , Lu Mei-Yeh Jade , Yang Kai-Jung , Li Mengyun , Teng Yuchuan , Chen Shihmay , Ku Maurice S. B. , Li Wen-Hsiung
Published: October 2016

The diploid C4 plant foxtail millet (Setaria italica L. Beauv.) is an important crop in many parts of Africa and Asia for the vast consumption of its grain and ability to grow in harsh environments, but remains understudied in terms of complete genomic architecture. To date, there have been only two genome assembly and annotation efforts with neither assembly reaching over 86% of the estimated genome size. We have combined de novo assembly with custom reference-guided improvements on a popular cultivar of foxtail millet and have achieved a genome assembly of 477 Mbp in length, which represents over 97% of the estimated 490 Mbp. The assembly anchors over 98% of the predicted genes to the nine assembled nuclear chromosomes and contains more functional annotation gene models than previous assemblies. Our annotation has identified a large number of unique gene ontology terms related to metabolic activities, a region of chromosome 9 with several growth factor proteins, and regions syntenic with pearl millet or maize genomic regions that have been previously shown to affect growth. The new assembly and annotation for this important species can be used for detailed investigation and future innovations in growth for millet and other grains.
The anticonvulsant retigabine suppresses neuronal KV2-mediated currents
Authors: Stas Jeroen I. , Bocksteins Elke , Jensen Camilla S. , Schmitt Nicole , Snyders Dirk J.
Published: October 2016

Enhancement of neuronal M-currents, generated through KV7.2-KV7.5 channels, has gained much interest for its potential in developing treatments for hyperexcitability-related disorders such as epilepsy. Retigabine, a KV7 channel opener, has proven to be an effective anticonvulsant and has recently also gained attention due to its neuroprotective properties. In the present study, we found that the auxiliary KCNE2 subunit reduced the KV7.2-KV7.3 retigabine sensitivity approximately 5-fold. In addition, using both mammalian expression systems and cultured hippocampal neurons we determined that low μM retigabine concentrations had ‘off-target’ effects on KV2.1 channels which have recently been implicated in apoptosis. Clinical retigabine concentrations (0.3–3 μM) inhibited KV2.1 channel function upon prolonged exposure. The suppression of the KV2.1 conductance was only partially reversible. Our results identified KV2.1 as a new molecular target for retigabine, thus giving a potential explanation for retigabine’s neuroprotective properties.
Large Tunable Thermophase in Superconductor – Quantum Dot – Superconductor Josephson Junctions
Authors: Kleeorin Yaakov , Meir Yigal , Giazotto Francesco , Dubi Yonatan
Published: October 2016

In spite of extended efforts, detecting thermoelectric effects in superconductors has proven to be a challenging task, due to the inherent superconducting particle-hole symmetry. Here we present a theoretical study of an experimentally attainable Superconductor – Quantum Dot – Superconductor (SC-QD-SC) Josephson Junction. Using Keldysh Green’s functions we derive the exact thermo-phase and thermal response of the junction, and demonstrate that such a junction has highly tunable thermoelectric properties and a significant thermal response. The origin of these effects is the QD energy level placed between the SCs, which breaks particle-hole symmetry in a gradual manner, allowing, in the presence of a temperature gradient, for gate controlled appearance of a superconducting thermo-phase. This thermo-phase increases up to a maximal value of ±π/2 after which thermovoltage is expected to develop. Our calculations are performed in realistic parameter regimes, and we suggest an experimental setup which could be used to verify our predictions.
Development of a one-pot assay for screening and identification of Mur pathway inhibitors in Mycobacterium tuberculosis
Authors: Eniyan Kandasamy , Kumar Anuradha , Rayasam Geetha Vani , Perdih Andrej , Bajpai Urmi
Published: October 2016

The cell wall of Mycobacterium tuberculosis (Mtb) consists of peptidoglycan, arabinogalactan and mycolic acids. The cytoplasmic steps in the peptidoglycan biosynthetic pathway, catalyzed by the Mur (A-F) enzymes, involve the synthesis of UDP-n-acetylmuramyl pentapeptide, a key precursor molecule required for the formation of the peptidoglycan monomeric building blocks. Mur enzymes are indispensable for cell integrity and their lack of counterparts in eukaryotes suggests them to be promising Mtb drug targets. However, the caveat is that most of the current assays utilize a single Mur enzyme, thereby identifying inhibitors against only one of the enzymes. Here, we report development of a one-pot assay that reconstructs the entire Mtb Mur pathway in vitro and has the advantage of eliminating the requirement for nucleotide intermediates in the pathway as substrates. The MurA-MurF enzymes were purified and a one-pot assay was developed through optimization of successive coupled enzyme assays using UDP-n-acetylglucosamine as the initial sugar substrate. The assay is biochemically characterized and optimized for high-throughput screening of molecules that could disrupt multiple targets within the pathway. Furthermore, we have validated the assay by performing it to identify D-Cycloserine and furan-based benzene-derived compounds with known Mur ligase inhibition as inhibitors of Mtb MurE and MurF.
Bacterial intra-species gene loss occurs in a largely clocklike manner mostly within a pool of less conserved and constrained genes
Authors: Bolotin Evgeni , Hershberg Ruth
Published: October 2016

Gene loss is a major contributor to the evolution of bacterial gene content. Gene loss may occur as a result of shifts in environment leading to changes in the intensity and/or directionality of selection applied for the maintenance of specific genes. Gene loss may also occur in a more neutral manner, when gene functions are lost that were not subject to strong selection to be maintained, irrespective of changes to environment. Here, we used a pangenome-based approach to investigate patterns of gene loss across 15 bacterial species. We demonstrate that gene loss tends to occur mostly within a pool of genes that are less constrained within species, even in those strains from which they are not lost, and less conserved across bacterial species. Our results indicate that shifts in selection, resulting from shifts in environment are not required to explain the majority of gene loss events occurring within a diverse collection of bacterial species. Caution should therefore be taken when attributing differences in gene content to differences in environment.
Thermal signatures of voluntary deception in ecological conditions
Authors: Panasiti Maria Serena , Cardone Daniela , Pavone Enea F. , Mancini Alessandra , Merla Arcangelo , Aglioti Salvatore M.
Published: October 2016

Deception is a pervasive phenomenon that greatly influences dyadic, groupal and societal interactions. Behavioural, physiological and neural signatures of this phenomenon have imporant implications for theoretical and applied research, but, because it is difficult for a laboratory to replicate the natural context in which deception occurs, contemporary research is still struggling to find such signatures. In this study, we tracked the facial temperature of participants who decided whether or not to deceive another person, in situations where their reputation was at risk or not. We used a high-sensitivity infrared device to track temperature changes to check for unique patterns of autonomic reactivity. Using a region-of-interest based approach we found that prior to any response there was a minimal increase in periorbital temperature (which indexes sympathetic activation, together with reduced cheek temperature) for the self-gain lies in the reputation-risk condition. Crucially, we found a rise in nose temperature (which indexes parasympathetic activation) for self-gain lies in the reputation-risk condition, not only during response preparation but also after the choice was made. This finding suggests that the entire deception process may be tracked by the nose region. Furthermore, this nasal temperature modulation was negatively correlated with machiavellian traits, indicating that sympathetic/parasympathetic regulation is less important for manipulative individuals who may care less about the consequences of lie-related moral violations. Our results highlight a unique pattern of autonomic reactivity for spontaneous deception in ecological contexts.
Early neuroimaging markers of FOXP2 intragenic deletion
Authors: Liégeois Frédérique J. , Hildebrand Michael S. , Bonthrone Alexandra , Turner Samantha J. , Scheffer Ingrid E. , Bahlo Melanie , Connelly Alan , Morgan Angela T.
Published: October 2016

FOXP2 is the major gene associated with severe, persistent, developmental speech and language disorders. While studies in the original family in which a FOXP2 mutation was found showed volume reduction and reduced activation in core language and speech networks, there have been no imaging studies of different FOXP2 mutations. We conducted a multimodal MRI study in an eight-year-old boy (A-II) with a de novo FOXP2 intragenic deletion. A-II showed marked bilateral volume reductions in the hippocampus, thalamus, globus pallidus, and caudate nucleus compared with 26 control males (effect sizes from −1 to −3). He showed no detectable functional MRI activity when repeating nonsense words. The hippocampus is implicated for the first time in FOXP2 diseases. We conclude that FOXP2 anomaly is either directly or indirectly associated with atypical development of widespread subcortical networks early in life.
The fecal microbiota as a biomarker for disease activity in Crohn’s disease
Authors: Tedjo Danyta. I. , Smolinska Agnieszka , Savelkoul Paul H. , Masclee Ad A. , van Schooten Frederik J. , Pierik Marieke J. , Penders John , Jonkers Daisy M. A. E.
Published: October 2016

Monitoring mucosal inflammation is crucial to prevent complications and disease progression in Crohn’s disease (CD). Endoscopy is the current standard, but is invasive. Clinical activity scores and non-invasive biochemical markers do not correlate well with mucosal inflammation. Microbial perturbations have been associated with disease activity in CD. Therefore, we aimed to investigate its potential use to differentiate CD patients in remission from those with an exacerbation. From 71 CD patients repeated fecal samples were collected, resulting in 97 active disease and 97 remission samples based on a combination of biochemical and clinical parameters. The microbiota composition was assessed by pyrosequencing of the 16S rRNA V1-V3 region. Random Forest analysis was used to find the most discriminatory panel of operational taxonomic units (OTUs) between active and remission samples. An independent internal validation set was used to validate the model. A combination of 50 OTUs was able to correctly predict 73% of remission and 79% of active samples with an AUC of 0.82 (sensitivity: 0.79, specificity: 0.73). This study demonstrates that fecal microbial profiles can be used to differentiate between active and remission CD and underline the potential of the fecal microbiota as a non-invasive tool to monitor disease activity in CD.
Characterization of a Ran gene from Puccinia striiformis f. sp. tritici involved in fungal growth and anti-cell death
Authors: Cheng Yulin , Yao Juanni , Zhang Yanru , Li Shumin , Kang Zhensheng
Published: October 2016

Ran, an important family of small GTP-binding proteins, has been shown to regulate a variety of important cellular processes in many eukaryotes. However, little is known about Ran function in pathogenic fungi. In this study, we report the identification and functional analysis of a Ran gene (designated PsRan) from Puccinia striiformis f. sp. tritici (Pst), an important fungal pathogen affecting wheat production worldwide. The PsRan protein contains all conserved domains of Ran GTPases and shares more than 70% identity with Ran proteins from other organisms, indicating that Ran proteins are conserved in different organisms. PsRan shows a low level of intra-species polymorphism and is localized to the nucleus. qRT-PCR analysis showed that transcript level of PsRan was induced in planta during Pst infection. Silencing of PsRan did not alter Pst virulence phenotype but impeded fungal growth of Pst. In addition, heterologous overexpression of PsRan in plant failed to induce cell death but suppressed cell death triggered by a mouse BAX gene or a Pst Ras gene. Our results suggest that PsRan is involved in the regulation of fungal growth and anti-cell death, which provides significant insight into Ran function in pathogenic fungi.
Core-shell Au-Pd nanoparticles as cathode catalysts for microbial fuel cell applications
Authors: Yang Gaixiu , Chen Dong , Lv Pengmei , Kong Xiaoying , Sun Yongming , Wang Zhongming , Yuan Zhenhong , Liu Hui , Yang Jun
Published: October 2016

Bimetallic nanoparticles with core-shell structures usually display enhanced catalytic properties due to the lattice strain created between the core and shell regions. In this study, we demonstrate the application of bimetallic Au-Pd nanoparticles with an Au core and a thin Pd shell as cathode catalysts in microbial fuel cells, which represent a promising technology for wastewater treatment, while directly generating electrical energy. In specific, in comparison with the hollow structured Pt nanoparticles, a benchmark for the electrocatalysis, the bimetallic core-shell Au-Pd nanoparticles are found to have superior activity and stability for oxygen reduction reaction in a neutral condition due to the strong electronic interaction and lattice strain effect between the Au core and the Pd shell domains. The maximum power density generated in a membraneless single-chamber microbial fuel cell running on wastewater with core-shell Au-Pd as cathode catalysts is ca. 16.0 W m−3 and remains stable over 150 days, clearly illustrating the potential of core-shell nanostructures in the applications of microbial fuel cells.
Solution-Processed One-Dimensional ZnO@CdS Heterojunction toward Efficient Cu2ZnSnS4 Solar Cell with Inverted Structure
Authors: Chen Rongrong , Fan Jiandong , Liu Chong , Zhang Xing , Shen Yanjiao , Mai Yaohua
Published: October 2016

Kesterite Cu2ZnSnS4 (CZTS) semiconductor has been demonstrated to be a promising alternative absorber in thin film solar cell in virtue of its earth-abundant, non-toxic element, suitable optical and electrical properties. Herein, a low-cost and non-toxic method that based on the thermal decomposition and reaction of metal-thiourea-oxygen sol-gel complexes to synthesize CZTS thin film was developed. The low-dimensional ZnO@CdS heterojunction nano-arrays coupling with the as-prepared CZTS thin film were employed to fabricate a novel solar cell with inverted structure. The vertically aligned nanowires (NWs) allow facilitating the charge carrier collection/separation/transfer with large interface areas. By optimizing the parameters including the annealing temperature of CZTS absorber, the thickness of CdS buffer layer and the morphology of ZnO NWs, an open-circuit voltage (VOC) as high as 589 mV was obtained by such solar cell with inverted structure. The all-solution-processed technic allows the realization of CZTS solar cell with extremely low cost.
Combined Transcriptomics and Chemical-Genetics Reveal Molecular Mode of Action of Valproic acid, an Anticancer Molecule using Budding Yeast Model
Authors: Golla Upendarrao , Joseph Deepthi , Tomar Raghuvir Singh
Published: October 2016

Valproic acid (VA) is a pharmacologically important histone deacetylase inhibitor that recently garnered attention as an anticancer agent. Since the molecular mechanisms behind the multiple effects of VA are unclear, this study was aimed to unravel the comprehensive cellular processes affected by VA and its molecular targets in vivo using budding yeast as a model organism. Interestingly, genome-wide transcriptome analysis of cells treated with VA showed differential regulation of 30% of the genome. Functional enrichment analysis of VA transcriptome evidenced alteration of various cellular processes including cell cycle, cell wall biogenesis, DNA repair, ion homeostasis, metabolism, stress response, transport and ribosomal biogenesis, etc. Moreover, our genetic screening analysis revealed VA molecular targets belonging to oxidative and osmotic stress, DNA repair, cell wall integrity, and iron homeostasis. Further, our results demonstrated the activation of mitogen-activated protein kinases (MAPKs) Hog1 (p38) and Slt2 (p44/42) upon VA treatment. Our results also exhibited that VA acts through alteration of mitochondrial, ER architecture and functions. Especially, VA effects were neutralized in cells lacking lipid particles. Altogether, our results deciphered the novel molecular insights and mechanistic links to strengthen our knowledge on diverse cellular effects of VA along with its probable therapeutic targets and detoxification approaches.
Differential responses of soil nematode community to pig manure application levels in Ferric Acrisols
Authors: Yang Yi-Ru , Li Xiao-Gang , Zhou Zhi-Gao , Zhang Tao-Lin , Wang Xing-Xiang
Published: October 2016

Excessive pig manure application probably degrades arable soil quality in some intensive pig farming areas. The responses of the nematode community to dosages of pig manure were investigated in Ferric Acrisols under 3-season peanut monoculture. Varying dosages of manure (1.75, 3.5, 7, 14 and 28 t·ha−1·yr−1) in combination with chemical fertilizer were applied to field plots, and chemical fertilizer alone was also applied as a control. With increasing manure application, the abundance of bacterivores and omnivores-predators increased, the abundance of plant parasites decreased, and fungivores abundance exhibited hump-shaped variation. Simpson diversity index and plant parasite index/maturity index of the nematode communities increased to a maximum level at a manure application rate of 3.5 t·ha−1·yr−1 and then sharply decreased. The changes in the soil nematode community were further determined to be correlated with chemical properties; available phosphorus had the strongest quadratic correlation with the two indices, implying that available phosphorus had a better indicative effect than other soil properties to nematode community. Available phosphorus in soil was deduced from 49 to 64 mg·kg−1 with the best nematode communities. Our results emphasized the importance of regular applications of manure in agriculture field to balance nematode diversity and build healthy agro-ecosystems.
Prioritizing cancer-related microRNAs by integrating microRNA and mRNA datasets
Authors: Jin Daeyong , Lee Hyunju
Published: October 2016

MicroRNAs (miRNAs) are small non-coding RNAs regulating the expression of target genes, and they are involved in cancer initiation and progression. Even though many cancer-related miRNAs were identified, their functional impact may vary, depending on their effects on the regulation of other miRNAs and genes. In this study, we propose a novel method for the prioritization of candidate cancer-related miRNAs that may affect the expression of other miRNAs and genes across the entire biological network. For this, we propose three important features: the average expression of a miRNA in multiple cancer samples, the average of the absolute correlation values between the expression of a miRNA and expression of all genes, and the number of predicted miRNA target genes. These three features were integrated using order statistics. By applying the proposed approach to four cancer types, glioblastoma, ovarian cancer, prostate cancer, and breast cancer, we prioritized candidate cancer-related miRNAs and determined their functional roles in cancer-related pathways. The proposed approach can be used to identify miRNAs that play crucial roles in driving cancer development, and the elucidation of novel potential therapeutic targets for cancer treatment.
Microenvironment complexity and matrix stiffness regulate breast cancer cell activity in a 3D in vitro model
Authors: Cavo Marta , Fato Marco , Peñuela Leonardo , Beltrame Francesco , Raiteri Roberto , Scaglione Silvia
Published: October 2016

Three-dimensional (3D) cell cultures represent fundamental tools for the comprehension of cellular phenomena both in normal and in pathological conditions. In particular, mechanical and chemical stimuli play a relevant role on cell fate, cancer onset and malignant evolution. Here, we use mechanically-tuned alginate hydrogels to study the role of substrate elasticity on breast adenocarcinoma cell activity. The hydrogel elastic modulus (E) was measured via atomic force microscopy (AFM) and a remarkable range (150–4000 kPa) was obtained. A breast cancer cell line, MCF-7, was seeded within the 3D gels, on standard Petri and alginate-coated dishes (2D controls). Cells showed dramatic morphological differences when cultured in 3D versus 2D, exhibiting a flat shape in both 2D conditions, while maintaining a circular, spheroid-organized (cluster) conformation within the gels, similar to those in vivo. Moreover, we observed a strict correlation between cell viability and substrate elasticity; in particular, the number of MCF-7 cells decreased constantly with increasing hydrogel elasticity. Remarkably, the highest cellular proliferation rate, associated with the formation of cell clusters, occurred at two weeks only in the softest hydrogels (E = 150–200 kPa), highlighting the need to adopt more realistic and a priori defined models for in vitro cancer studies.
Identification of the Photoreceptor Transcriptional Co-Repressor SAMD11 as Novel Cause of Autosomal Recessive Retinitis Pigmentosa
Authors: Corton M. , Avila-Fernández A. , Campello L. , Sánchez M. , Benavides B. , López-Molina M. I. , Fernández-Sánchez L. , Sánchez-Alcudia R. , da Silva L. R. J. , Reyes N. , Martín-Garrido E. , Zurita O. , Fernández-San José P. , Pérez-Carro R. , García-García F. , Dopazo J. , García-Sandoval B. , Cuenca N. , Ayuso C.
Published: October 2016

Retinitis pigmentosa (RP), the most frequent form of inherited retinal dystrophy is characterized by progressive photoreceptor degeneration. Many genes have been implicated in RP development, but several others remain to be identified. Using a combination of homozygosity mapping, whole-exome and targeted next-generation sequencing, we found a novel homozygous nonsense mutation inSAMD11in five individuals diagnosed with adult-onset RP from two unrelated consanguineous Spanish families. SAMD11 is ortholog to the mouse major retinal SAM domain (mr-s) protein that is implicated in CRX-mediated transcriptional regulation in the retina. Accordingly, protein-protein network analysis revealed a significant interaction of SAMD11 with CRX. Immunoblotting analysis confirmed strong expression of SAMD11 in human retina. Immunolocalization studies revealed SAMD11 was detected in the three nuclear layers of the human retina and interestingly differential expression between cone and rod photoreceptors was observed. Our study strongly implicatesSAMD11as novel cause of RP playing an important role in the pathogenesis of human degeneration of photoreceptors.
Rapid Detection of Necrosis in Breast Cancer with Desorption Electrospray Ionization Mass Spectrometry
Authors: Tata Alessandra , Woolman Michael , Ventura Manuela , Bernards Nicholas , Ganguly Milan , Gribble Adam , Shrestha Bindesh , Bluemke Emma , Ginsberg Howard J. , Vitkin Alex , Zheng Jinzi , Zarrine-Afsar Arash
Published: October 2016

Identification of necrosis in tumors is of prognostic value in treatment planning, as necrosis is associated with aggressive forms of cancer and unfavourable outcomes. To facilitate rapid detection of necrosis with Mass Spectrometry (MS), we report the lipid MS profile of necrotic breast cancer with Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) imaging validated with statistical analysis and correlating pathology. This MS profile is characterized by (1) the presence of the ion of m/z 572.48 [Cer(d34:1) + Cl]− which is a ceramide absent from the viable cancer subregions; (2) the absence of the ion of m/z 391.25 which is present in small abundance only in viable cancer subregions; and (3) a slight increase in the relative intensity of known breast cancer biomarker ions of m/z 281.25 [FA(18:1)-H]− and 303.23 [FA(20:4)-H]−. Necrosis is accompanied by alterations in the tissue optical depolarization rate, allowing tissue polarimetry to guide DESI-MS analysis for rapid MS profiling or targeted MS imaging. This workflow, in combination with the MS profile of necrosis, may permit rapid characterization of necrotic tumors from tissue slices. Further, necrosis-specific biomarker ions are detected in seconds with single MS scans of necrotic tumor tissue smears, which further accelerates the identification workflow by avoiding tissue sectioning and slide preparation.
Effects of light acclimation on shoot morphology, structure, and biomass allocation of two Taxus species in southwestern China
Authors: Liu Wande , Su Jianrong
Published: October 2016

Acclimation to changing light conditions plays a crucial role in determining the competitive capability of tree species. There is currently limited information about acclimation to natural light gradient and its effect on shoot structure and biomass in Taxus species. We examined the acclimation of the leaf and shoot axis morphology, structure and biomass allocation of Taxus yunnanensis and T. chinensis var. mairei under three different natural light environments, full daylight, 40–60% full daylight and <10% full daylight. The leaf biomass, nitrogen content per unit area, leaf carbon content per dry mass and leaf dry mass to fresh mass ratio increased with light in both species, demonstrating an enhanced investment of photosynthetic biomass and structural investment under high light. The number of leaves per unit shoot axis length and the leaf dry mass per unit shoot axis length increased with light in both species. However, the light increase did not result in the increase of the total shoot mass. T. yunnanensis produced larger leaves under low light and a higher shoot axis length per unit dry mass under high light, whereas the leaf size and biomass yield of T. chinensis var. mairei were not sensitive to light.