bluuebunny/crossref_metadata_2025 huggingface dataset:
Differentially expressed genes related to major depressive disorder and antidepressant response: genome-wide gene expression analysis
Authors: Woo Hye In , Lim Shinn-Won , Myung Woojae , Kim Doh Kwan , Lee Soo-Youn
Published: August 2018

Treatment response to antidepressants is limited and varies among patients with major depressive disorder (MDD). To discover genes and mechanisms related to the pathophysiology of MDD and antidepressant treatment response, we performed gene expression analyses using peripheral blood specimens from 38 MDD patients and 14 healthy individuals at baseline and at 6 weeks after the initiation of either selective serotonin reuptake inhibitor (SSRI) or mirtazapine treatment. The results were compared with results from public microarray data. Seven differentially expressed genes (DEGs) between MDD patients and controls were identified in our study and in the public microarray data: CD58, CXCL8, EGF, TARP, TNFSF4, ZNF583, and ZNF587. CXCL8 was among the top 10 downregulated genes in both studies. Eight genes related to SSRI responsiveness, including BTNL8, showed alterations in gene expression in MDD. The expression of the FCRL6 gene differed between SSRI responders and nonresponders and changed after SSRI treatment compared to baseline. In evaluating the response to mirtazapine, 21 DEGs were identified when comparing MDD patients and controls and responders and nonresponders. These findings suggest that the pathophysiology of MDD and treatment response to antidepressants are associated with a number of processes, including DNA damage and apoptosis, that can be induced by immune activation and inflammation.
Late Cenozoic unification of East and West Antarctica
Authors: Granot Roi , Dyment Jérôme
Published: August 2018

The kinematic evolution of the West Antarctic rift system has important consequences for regional and global geodynamics. However, due to the lack of Neogene seafloor spreading at the plate boundary and despite being poorly resolved, East-West Antarctic motion was assumed to have ended abruptly at 26 million years ago. Here we present marine magnetic data collected near the northern edge of the rift system showing that motion between East and West Antarctica lasted until the middle Neogene (~11 million years ago), long after the cessation of the known mid-Cenozoic pulse of motion. We calculate new rotation parameters for the early Neogene that provide the kinematic framework to understand the varied lithospheric settings of the Transantarctic Mountains and the tectono–volcanic activity within the rift. Incorporation of the Antarctic plate motion into the global plate circuit has major implications for the predicted Neogene motion of the Pacific Plate relative to the rest of the plates.
Identification of recurrent USP48 and BRAF mutations in Cushing’s disease
Authors: Chen Jianhua , Jian Xuemin , Deng Siyu , Ma Zengyi , Shou Xuefei , Shen Yue , Zhang Qilin , Song Zhijian , Li Zhiqiang , Peng Hong , Peng Cheng , Chen Min , Luo Cheng , Zhao Dan , Ye Zhao , Shen Ming , Zhang Yichao , Zhou Juan , Fahira Aamir , Wang Yongfei , Li Shiqi , Zhang Zhaoyun , Ye Hongying , Li Yiming , Shen Jiawei , Chen Hong , Tang Feng , Yao Zhenwei , Shi Zhifeng , Chen Chunjui , Xie Lu , Wang Ye , Fu Chaowei , Mao Ying , Zhou Liangfu , Gao Daming , Yan Hai , Zhao Yao , Huang Chuanxin , Shi Yongyong
Published: August 2018

Cushing’s disease results from corticotroph adenomas of the pituitary that hypersecrete adrenocorticotropin (ACTH), leading to excess glucocorticoid and hypercortisolism. Mutations of the deubiquitinase gene USP8 occur in 35–62% of corticotroph adenomas. However, the major driver mutations in USP8 wild-type tumors remain elusive. Here, we report recurrent mutations in the deubiquitinase gene USP48 (predominantly encoding p.M415I or p.M415V; 21/91 subjects) and BRAF (encoding p.V600E; 15/91 subjects) in corticotroph adenomas with wild-type USP8. Similar to USP8 mutants, both USP48 and BRAF mutants enhance the promoter activity and transcription of the gene encoding proopiomelanocortin (POMC), which is the precursor of ACTH, providing a potential mechanism for ACTH overproduction in corticotroph adenomas. Moreover, primary corticotroph tumor cells harboring BRAF V600E are sensitive to the BRAF inhibitor vemurafenib. Our study thus contributes to the understanding of the molecular mechanism of the pathogenesis of corticotroph adenoma and informs therapeutic targets for this disease.
Role of VTA dopamine neurons and neuroligin 3 in sociability traits related to nonfamiliar conspecific interaction
Authors: Bariselli Sebastiano , Hörnberg Hanna , Prévost-Solié Clément , Musardo Stefano , Hatstatt-Burklé Laetitia , Scheiffele Peter , Bellone Camilla
Published: August 2018

Atypical habituation and aberrant exploration of novel stimuli have been related to the severity of autism spectrum disorders (ASDs), but the underlying neuronal circuits are unknown. Here we show that chemogenetic inhibition of dopamine (DA) neurons of the ventral tegmental area (VTA) attenuates exploration toward nonfamiliar conspecifics and interferes with the reinforcing properties of nonfamiliar conspecific interaction in mice. Exploration of nonfamiliar stimuli is associated with the insertion of GluA2-lacking AMPA receptors at excitatory synapses on VTA DA neurons. These synaptic adaptations persist upon repeated exposure to social stimuli and sustain conspecific interaction. Global or VTA DA neuron-specific loss of the ASD-associated synaptic adhesion molecule neuroligin 3 alters the behavioral response toward nonfamiliar conspecifics and the reinforcing properties of conspecific interaction. These behavioral deficits are accompanied by an aberrant expression of AMPA receptors and an occlusion of synaptic plasticity. Altogether, these findings link impaired exploration of nonfamiliar conspecifics to VTA DA neuron dysfunction in mice.
Perturbation to the nitrogen cycle during rapid Early Eocene global warming
Authors: Junium Christopher K. , Dickson Alexander J. , Uveges Benjamin T.
Published: August 2018

The degree to which ocean deoxygenation will alter the function of marine communities remains unclear but may be best constrained by detailed study of intervals of rapid warming in the geologic past. The Paleocene–Eocene Thermal Maximum (PETM) was an interval of rapid warming that was the result of increasing contents of greenhouse gases in the atmosphere that had wide ranging effects on ecosystems globally. Here, we present stable nitrogen isotope data from the Eastern Peri-Tethys Ocean that record a significant transition in the nitrogen cycle. At the initiation of the PETM, the nitrogen isotopic composition of sediments decreased by ~6‰ to as low as −3.4‰, signaling reorganization of the marine nitrogen cycle. Warming, changes in ocean circulation, and deoxygenation caused a transition to nitrogen cycle to conditions that were most similar to those experienced during Oceanic Anoxic Events of the Mesozoic.
T cell-intrinsic IL-1R signaling licenses effector cytokine production by memory CD4 T cells
Authors: Jain Aakanksha , Song Ran , Wakeland Edward K. , Pasare Chandrashekhar
Published: August 2018

Innate cytokines are critical drivers of priming and differentiation of naive CD4 T cells, but their functions in memory T cell response are largely undefined. Here we show that IL-1 acts as a licensing signal to permit effector cytokine production by pre-committed Th1 (IFN-γ), Th2 (IL-13, IL-4, and IL-5) and Th17 (IL-17A, IL-17F, and IL-22) lineage cells. This licensing function of IL-1 is conserved across effector CD4 T cells generated by diverse immunological insults. IL-1R signaling stabilizes cytokine transcripts to enable productive and rapid effector functions. We also demonstrate that successful lineage commitment does not translate into productive effector functions in the absence of IL-1R signaling. Acute abrogation of IL-1R signaling in vivo results in reduced IL-17A production by intestinal Th17 cells. These results extend the role of innate cytokines beyond CD4 T cell priming and establish IL-1 as a licensing signal for memory CD4 T cell function.
Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility
Authors: Machiela Mitchell J. , Grünewald Thomas G. P. , Surdez Didier , Reynaud Stephanie , Mirabeau Olivier , Karlins Eric , Rubio Rebeca Alba , Zaidi Sakina , Grossetete-Lalami Sandrine , Ballet Stelly , Lapouble Eve , Laurence Valérie , Michon Jean , Pierron Gaelle , Kovar Heinrich , Gaspar Nathalie , Kontny Udo , González-Neira Anna , Picci Piero , Alonso Javier , Patino-Garcia Ana , Corradini Nadège , Bérard Perrine Marec , Freedman Neal D. , Rothman Nathaniel , Dagnall Casey L. , Burdett Laurie , Jones Kristine , Manning Michelle , Wyatt Kathleen , Zhou Weiyin , Yeager Meredith , Cox David G. , Hoover Robert N. , Khan Javed , Armstrong Gregory T. , Leisenring Wendy M. , Bhatia Smita , Robison Leslie L. , Kulozik Andreas E. , Kriebel Jennifer , Meitinger Thomas , Metzler Markus , Hartmann Wolfgang , Strauch Konstantin , Kirchner Thomas , Dirksen Uta , Morton Lindsay M. , Mirabello Lisa , Tucker Margaret A. , Tirode Franck , Chanock Stephen J. , Delattre Olivier
Published: August 2018

Ewing sarcoma (EWS) is a pediatric cancer characterized by the EWSR1-FLI1 fusion. We performed a genome-wide association study of 733 EWS cases and 1346 unaffected individuals of European ancestry. Our study replicates previously reported susceptibility loci at 1p36.22, 10q21.3 and 15q15.1, and identifies new loci at 6p25.1, 20p11.22 and 20p11.23. Effect estimates exhibit odds ratios in excess of 1.7, which is high for cancer GWAS, and striking in light of the rarity of EWS cases in familial cancer syndromes. Expression quantitative trait locus (eQTL) analyses identify candidate genes at 6p25.1 (RREB1) and 20p11.23 (KIZ). The 20p11.22 locus is near NKX2-2, a highly overexpressed gene in EWS. Interestingly, most loci reside near GGAA repeat sequences and may disrupt binding of the EWSR1-FLI1 fusion protein. The high locus to case discovery ratio from 733 EWS cases suggests a genetic architecture in which moderate risk SNPs constitute a significant fraction of risk.
A Late Cretaceous amber biota from central Myanmar
Authors: Zheng Daran , Chang Su-Chin , Perrichot Vincent , Dutta Suryendu , Rudra Arka , Mu Lin , Thomson Ulysses , Li Sha , Zhang Qi , Zhang Qingqing , Wong Jean , Wang Jun , Wang He , Fang Yan , Zhang Haichun , Wang Bo
Published: August 2018

Insect faunas are extremely rare near the latest Cretaceous with a 24-million-year gap spanning from the early Campanian to the early Eocene. Here, we report a unique amber biota from the Upper Cretaceous (uppermost Campanian ~72.1 Ma) of Tilin, central Myanmar. The chemical composition of Tilin amber suggests a tree source among conifers, indicating that gymnosperms were still abundant in the latest Campanian equatorial forests. Eight orders and 12 families of insects have been found in Tilin amber so far, making it the latest known diverse insect assemblage in the Mesozoic. The presence of ants of the extant subfamilies Dolichoderinae and Ponerinae supports that tropical forests were the cradle for the diversification of crown-group ants, and suggests that the turnover from stem groups to crown groups had already begun at ~72.1 Ma. Tilin amber biota fills a critical insect faunal gap and provides a rare insight into the latest Campanian forest ecosystem.
Post-drought decline of the Amazon carbon sink
Authors: Yang Yan , Saatchi Sassan S. , Xu Liang , Yu Yifan , Choi Sungho , Phillips Nathan , Kennedy Robert , Keller Michael , Knyazikhin Yuri , Myneni Ranga B.
Published: August 2018

Amazon forests have experienced frequent and severe droughts in the past two decades. However, little is known about the large-scale legacy of droughts on carbon stocks and dynamics of forests. Using systematic sampling of forest structure measured by LiDAR waveforms from 2003 to 2008, here we show a significant loss of carbon over the entire Amazon basin at a rate of 0.3 ± 0.2 (95% CI) PgC yr−1 after the 2005 mega-drought, which continued persistently over the next 3 years (2005–2008). The changes in forest structure, captured by average LiDAR forest height and converted to above ground biomass carbon density, show an average loss of 2.35 ± 1.80 MgC ha−1 a year after (2006) in the epicenter of the drought. With more frequent droughts expected in future, forests of Amazon may lose their role as a robust sink of carbon, leading to a significant positive climate feedback and exacerbating warming trends.
PI3Kδ hyper-activation promotes development of B cells that exacerbate Streptococcus pneumoniae infection in an antibody-independent manner
Authors: Stark Anne-Katrien , Chandra Anita , Chakraborty Krishnendu , Alam Rafeah , Carbonaro Valentina , Clark Jonathan , Sriskantharajah Srividya , Bradley Glyn , Richter Alex G. , Banham-Hall Edward , Clatworthy Menna R. , Nejentsev Sergey , Hamblin J. Nicole , Hessel Edith M. , Condliffe Alison M. , Okkenhaug Klaus
Published: August 2018

Streptococcus pneumoniaeis a major cause of pneumonia and a leading cause of death world-wide. Antibody-mediated immune responses can confer protection against repeated exposure toS. pneumoniae, yet vaccines offer only partial protection. Patients with Activated PI3Kδ Syndrome (APDS) are highly susceptible toS. pneumoniae. We generated a conditional knock-in mouse model of this disease and identify a CD19+B220−B cell subset that is induced by PI3Kδ signaling, resides in the lungs, and is correlated with increased susceptibility toS. pneumoniaeduring early phases of infection via an antibody-independent mechanism. We show that an inhaled PI3Kδ inhibitor improves survival rates followingS. pneumoniaeinfection in wild-type mice and in mice with activated PI3Kδ. These results suggest that a subset of B cells in the lung can promote the severity ofS. pneumoniaeinfection, representing a potential therapeutic target.
High-resolution visualization of H3 variants during replication reveals their controlled recycling
Authors: Clément Camille , Orsi Guillermo A. , Gatto Alberto , Boyarchuk Ekaterina , Forest Audrey , Hajj Bassam , Miné-Hattab Judith , Garnier Mickaël , Gurard-Levin Zachary A. , Quivy Jean-Pierre , Almouzni Geneviève
Published: August 2018

DNA replication is a challenge for the faithful transmission of parental information to daughter cells, as both DNA and chromatin organization must be duplicated. Replication stress further complicates the safeguard of epigenome integrity. Here, we investigate the transmission of the histone variants H3.3 and H3.1 during replication. We follow their distribution relative to replication timing, first in the genome and, second, in 3D using super-resolution microscopy. We find that H3.3 and H3.1 mark early- and late-replicating chromatin, respectively. In the nucleus, H3.3 forms domains, which decrease in density throughout replication, while H3.1 domains increase in density. Hydroxyurea impairs local recycling of parental histones at replication sites. Similarly, depleting the histone chaperone ASF1 affects recycling, leading to an impaired histone variant landscape. We discuss how faithful transmission of histone variants involves ASF1 and can be impacted by replication stress, with ensuing consequences for cell fate and tumorigenesis.
Quantum coherence of multiple excitons governs absorption cross-sections of PbS/CdS core/shell nanocrystals
Authors: Tahara Hirokazu , Sakamoto Masanori , Teranishi Toshiharu , Kanemitsu Yoshihiko
Published: August 2018

Multiple excitons in semiconductor nanocrystals have been extensively studied with respect to unique carrier dynamics including quantized Auger recombination and implementation in optoelectronic devices such as solar cells and photodetectors. However, the generation mechanism of multiple excitons still remains unclear. Here, we study instantaneous and delayed multiple exciton generation processes in PbS/CdS core/shell nanocrystals. The absorption cross-sections of biexcitons and triexcitons are identical to that of single excitons under instantaneous excitation with a single pulse. In contrast, the delayed excitation using double pulses shows a reduction of the biexciton and triexciton absorption cross-sections. Our theoretical analysis reveals that the excitonic coherence assists the generation of multiple excitons and that the reduction of multiple exciton absorption cross-sections is caused by the reduction of coherent excitation pathways. We clarify that exciton coherences play a key role in multiple exciton generation processes and seamlessly connect the identical and reduced multiple exciton absorption cross-sections.
Resistance to retinopathy development in obese, diabetic and hypertensive ZSF1 rats: an exciting model to identify protective genes
Authors: Caolo Vincenza , Roblain Quentin , Lecomte Julie , Carai Paolo , Peters Linsey , Cuijpers Ilona , Robinson Emma Louise , Derks Kasper , Sergeys Jurgen , Noël Agnès , Jones Elizabeth A. V. , Moons Lieve , Heymans Stephane
Published: August 2018

Diabetic retinopathy (DR) is one of the major complications of diabetes, which eventually leads to blindness. Up to date, no animal model has yet shown all the co-morbidities often observed in DR patients. Here, we investigated whether obese 42 weeks old ZSF1 rat, which spontaneously develops diabetes, hypertension and obesity, would be a suitable model to study DR. Although arteriolar tortuosity increased in retinas from obese as compared to lean (hypertensive only) ZSF1 rats, vascular density pericyte coverage, microglia number, vascular morphology and retinal thickness were not affected by diabetes. These results show that, despite high glucose levels, obese ZSF1 rats did not develop DR. Such observations prompted us to investigate whether the expression of genes, possibly able to contain DR development, was affected. Accordingly, mRNA sequencing analysis showed that genes (i.e. Npy and crystallins), known to have a protective role, were upregulated in retinas from obese ZSF1 rats. Lack of retina damage, despite obesity, hypertension and diabetes, makes the 42 weeks of age ZSF1 rats a suitable animal model to identify genes with a protective function in DR. Further characterisation of the identified genes and downstream pathways could provide more therapeutic targets for the treat DR.
Tetrahedral honeycomb surface reconstructions of quartz, cristobalite and stishovite
Authors: Feya Oleg D. , Wang Qinggao , Lepeshkin Sergey V. , Baturin Vladimir S. , Uspenskii Yurii A. , Oganov Artem R.
Published: August 2018

Crystalline silica (SiO2) is a major material used in many technologies, yet the exact surface structures of silica polymorphs are still mostly unknown. Here we perform a comprehensive study of surface reconstructions of α-cristobalite (001), α-quartz (001) and stishovite (110) and (100) using evolutionary algorithm USPEX in conjunction with ab initio calculations. We found the well-known “dense surface” to be among low-energy reconstructions of α-quartz (001), as well as its previously proposed distorted version, which we call “shifted surface”. For cristobalite and stishovite we show the formation of reconstructions without dangling bonds which share common features with well-known “dense surface” of α-quartz (001). We call them “dense cristobalite” and “dense stishovite” – all of these have honeycomb arrangements of corner-sharing SiO4-tetrahedra in the surface layers. These tetrahedral honeycombs have very low surface energies, and such tetrahedral surface pattern is observed even in stishovite (the bulk structure of which has SiO6-octahedra, rather than SiO4-tetrahedra).
The Role of Nano-domains in {1–011} Twinned Martensite in Metastable Titanium Alloys
Authors: Lee Sangwon , Park Chanhee , Hong Jaekeun , Yeom Jong-taek
Published: August 2018

The formation mechanism of $${\{\bar{{\bf{1}}}{\bf{011}}\}}_{{\boldsymbol{\alpha }}{\boldsymbol{^{\prime} }}}$$

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type twinned α′-martensitic structures was investigated in titanium alloys, and in-depth characterizations of the microstructures were performed using scanning electron microscopy and transmission electron microscopy. The randomly distributed nano-domains nucleated by water quenching were sheared during the primary martensite transformation. Experimental results revealed that this sheared nano-domain interferes with the primary martensite transformation and induces a secondary martensite transformation. In terms of crystallography, the secondary martensite transformed from the sheared nano-domain has a $${\{\bar{{\bf{1}}}{\bf{011}}\}}_{{\boldsymbol{\alpha }}{\boldsymbol{^{\prime} }}}$$

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type twin relationship with the primary martensite. The growth of both martensites yielded a more twinned martensitic structure as the applied strain increased.
A nuclear-encoded protein, mTERF6, mediates transcription termination of rpoA polycistron for plastid-encoded RNA polymerase-dependent chloroplast gene expression and chloroplast development
Authors: Zhang Yi , Cui Yong-Lan , Zhang Xiao-Lei , Yu Qing-Bo , Wang Xi , Yuan Xin-Bo , Qin Xue-Mei , He Xiao-Fang , Huang Chao , Yang Zhong-Nan
Published: August 2018

The expression of plastid genes is regulated by two types of DNA-dependent RNA polymerases, plastid-encoded RNA polymerase (PEP) and nuclear-encoded RNA polymerase (NEP). The plastid rpoA polycistron encodes a series of essential chloroplast ribosome subunits and a core subunit of PEP. Despite the functional importance, little is known about the regulation of rpoA polycistron. In this work, we show that mTERF6 directly associates with a 3′-end sequence of rpoA polycistron in vitro and in vivo, and that absence of mTERF6 promotes read-through transcription at this site, indicating that mTERF6 acts as a factor required for termination of plastid genes’ transcription in vivo. In addition, the transcriptions of some essential ribosome subunits encoded by rpoA polycistron and PEP-dependent plastid genes are reduced in the mterf6 knockout mutant. RpoA, a PEP core subunit, accumulates to about 50% that of the wild type in the mutant, where early chloroplast development is impaired. Overall, our functional analyses of mTERF6 provide evidence that it is more likely a factor required for transcription termination of rpoA polycistron, which is essential for chloroplast gene expression and chloroplast development.
Monetary Incentives Modulate Feedback-related Brain Activity
Authors: Mei Shuting , Li Qi , Liu Xun , Zheng Ya
Published: August 2018

Previous research has shown that feedback evaluation is sensitive to monetary incentive. We investigated whether this sensitivity is driven by motivational salience (the difference between both rewarding and punishing events versus neutral events) or by motivational valence (the difference between rewarding and punishing events). Fifty-seven participants performed a monetary incentive delay task under a gain context, a loss context, and a neutral context with their electroencephalogram recorded. During the time domain, the feedback-related negativity (FRN) showed a motivational salience effect whereas the P3 displayed a reward valence effect. During the time-frequency domain, we observed a motivational salience effect for phase-locked theta power regardless of performance feedback, but a reward valence effect for non-phase-locked theta power in response to unsuccessful feedback. Moreover, we found a reward valence effect for phase-locked delta. These findings thus suggest that the affective modulation on feedback evaluation can be driven either by motivational valence or by motivational salience, which depends on the temporal dynamics (the FRN vs. the P3), the frequency dynamics (theta vs. delta power), as well as the phase dynamics (evoked vs. induced power).
Short and Long-Term Potential Role of Carbon Nanoparticles in Total Thyroidectomy with Central Lymph Node Dissection
Authors: Xue Shuai , Ren Peiyou , Wang Peisong , Chen Guang
Published: August 2018

Whether we should use carbon nanoparticle (CN) routinely in thyroid surgery is still controversial. 406 papillary thyroid cancer (PTC) patients who underwent total thyroidectomy (TT) with bilateral central lymph node dissection (CLND) from January 2010 to December 2012 were retrospectively analyzed. The incidence of transient hypoparathyroidism and hypocalcemia in CN group was significantly lower than the control group at second, fifth day after surgery (P = 0.004, 0.042, 0.002 and 0.045 respectively). However, no significant difference existed between the two groups about the permanent hypoparathyroidism and hypocalcemia (P = 1.000). Total number of central lymph nodes and metastatic lymph nodes in CN group were more than those in control group (P = 0.031 and 0.038 respectively). However, recurrence was not significantly different between the two groups after at least 5-year follow up (P = 0.7917). In the subgroup of prophylactic and therapeutic CLND study, no significant difference existed between the two groups (P = 0.5295 and 0.8459 respectively). CN significantly help in identifying the parathyroid glands in surgery and increased the number of lymph nodes in central compartment. However, we should not exaggerate the function of CN since it couldn’t improve the permanent hypoparathyroidism and recurrence in PTC patients who underwent TT with bilateral CLND.
Identification of influential spreaders in complex networks using HybridRank algorithm
Authors: Ahajjam Sara , Badir Hassan
Published: August 2018

Identifying the influential spreaders in complex networks is crucial to understand who is responsible for the spreading processes and the influence maximization through networks. Targeting these influential spreaders is significant for designing strategies for accelerating the propagation of information that is useful for various applications, such as viral marketing applications or blocking the diffusion of annoying information (spreading of viruses, rumors, online negative behaviors, and cyberbullying). Existing methods such as local centrality measures like degree centrality are less effective, and global measures like closeness and betweenness centrality could better identify influential spreaders but they have some limitations. In this paper, we propose the HybridRank algorithm using a new hybrid centrality measure for detecting a set of influential spreaders using the topological features of the network. We use the SIR spreading model for simulating the spreading processes in networks to evaluate the performance of our algorithm. Empirical experiments are conducted on real and artificial networks, and the results show that the spreaders identified by our approach are more influential than several benchmarks.
Clock gene expression and locomotor activity predict death in the last days of life in Drosophila melanogaster
Authors: Zhao Jia , Warman Guy Robert , Cheeseman James Frederick
Published: August 2018

The importance of the circadian clock for the regulation of behaviour and physiology, and the molecular control of these rhythms by a set of clock genes are well defined. The circadian clock deteriorates with advancing age but the mechanism underlying is unclear. Here we recorded the expression of two key clock genes in young, middle-aged and old Drosophila using transgenic luciferase lines reporting period and timeless in vivo. We report a novel marker of imminent death in the expression of TIMELESS. In the days immediately preceding death TIMELESS expression increased to at least 150% of previous acrophase values (88.0% of n = 217) and lost circadian rhythmicity, which predicted death equally well in flies of different ages and under light and temperature cycles. We suggest this transient aberrant clock-gene expression is central to the mechanism of the disturbance in circadian behaviour before death (82.7% of n = 342). We also find that PERIOD expression in central-clock neurons remained robust with age, however PERIOD and TIMELESS in peripheral clocks showed a reduction in both expression level and rhythmicity. In conclusion, as flies age the molecular clock gradually declines at the peripheral level but continues to function at the central until days before death.
Significant enhancement of nitrous oxide energy yields from wastewater achieved by bioaugmentation with a recombinant strain of Pseudomonas aeruginosa
Authors: Lin Ziyu , Sun Dezhi , Dang Yan , Holmes Dawn E.
Published: August 2018

Nitrous oxide (N2O) is formed during wastewater nitrogen removal processes. It is a strong greenhouse gas, however, if properly captured it can also be used as a renewable energy source. In this study, a nosZ-deficient strain of Pseudomonas aeruginosa was constructed. During growth under denitrifying conditions, the nosZ-deficient strain was more highly transcribing other genes from the denitrification pathway (narG, nirS, and norB) than the wild-type strain. This strain could also convert 85% of NO2−-N to N2O when it was grown with acetate compared to <0.6% by the wild-type strain. When a bioreactor treating synthetic wastewater with high NO2−-N concentrations (700 mg/L) was inoculated with this strain, the N2O conversion efficiencies were >73% and N2O comprised 73~81% of the biogas being generated. The energy yield from wastewater in bioaugmented reactors also reached levels as high as 1260 kJ/m3. These results are significant and show that bioaugmentation of reactors during denitrification treatment processes with nosZ-deficient strains of Pseudomonas or other core denitrifying bacteria might be an effective way to enhance N2O recovery.
c-Src regulates cargo transit via the Golgi in pancreatic acinar cells
Authors: Kostenko Sergiy , Heu Chan C. , Yaron Jordan R. , Singh Garima , de Oliveira Cristiane , Muller William J. , Singh Vijay P.
Published: August 2018

The exocrine pancreatic acinar cell is unique for its rapid protein synthesis and packaging in zymogen granules (ZGs). However, while crucial to the pathogenesis of pancreatitis, the signaling involved in the transit of proteins via the Golgi is poorly understood in these cells. Noting the evidence of c-Src in regulating transit of cargo via the Golgi in other systems, we explored this in acinar cells. Stimulation of ZG formation with dexamethasone activated Src and increased the Golgi area in acinar cells. c-Src localized to the microsomes of acinar cells on immunofluorescence and subcellular fractionation. While other Src family members had no effect on the Golgi markers P115 and GM130, active c-Src increased the Golgi area these stained, extending them into the ER. Src inhibition reduced amylase staining outside the Golgi and increased it in a stack like Golgi morphology. In vivo pharmacologic inhibition or acinar specific genetic deletion of c-Src reduced ZG number and staining of amylase in ZGs along with increasing amylase retention in the microsomal fraction. Morphologically this was associated with smaller Golgi stacks, and dilation of the endoplasmic reticulum. Therefore the role c-Src regulated Golgi function, ZG formation and microsomal zymogen transit in acinar cells needs to be explored in pancreatitis.
Suboptimal Coding Metasurfaces for Terahertz Diffuse Scattering
Authors: Moccia Massimo , Koral Can , Papari Gian Paolo , Liu Shuo , Zhang Lei , Wu Rui Yuan , Castaldi Giuseppe , Cui Tie Jun , Galdi Vincenzo , Andreone Antonello
Published: August 2018

Coding metasurfaces, composed of only two types of elements arranged according to a binary code, are attracting a steadily increasing interest in many application scenarios. In this study, we apply this concept to attain diffuse scattering at THz frequencies. Building up on previously derived theoretical results, we carry out a suboptimal metasurface design based on a simple, deterministic and computationally inexpensive algorithm that can be applied to arbitrarily large structures. For experimental validation, we fabricate and characterize three prototypes working at 1 THz, which, in accordance with numerical predictions, exhibit significant reductions of the radar cross-section, with reasonably good frequency and angular stability. Besides the radar-signature control, our results may also find potentially interesting applications to diffusive imaging, computational imaging, and (scaled to optical wavelengths) photovoltaics.
A single N1-methyladenosine on the large ribosomal subunit rRNA impacts locally its structure and the translation of key metabolic enzymes
Authors: Sharma Sunny , Hartmann Johannes David , Watzinger Peter , Klepper Arvid , Peifer Christian , Kötter Peter , Lafontaine Denis L. J. , Entian Karl-Dieter
Published: August 2018

The entire chemical modification repertoire of yeast ribosomal RNAs and the enzymes responsible for it have recently been identified. Nonetheless, in most cases the precise roles played by these chemical modifications in ribosome structure, function and regulation remain totally unclear. Previously, we demonstrated that yeast Rrp8 methylates m1A645 of 25S rRNA in yeast. Here, using mung bean nuclease protection assays in combination with quantitative RP-HPLC and primer extension, we report that 25S/28S rRNA of S. pombe, C. albicans and humans also contain a single m1A methylation in the helix 25.1. We characterized nucleomethylin (NML) as a human homolog of yeast Rrp8 and demonstrate that NML catalyzes the m1A1322 methylation of 28S rRNA in humans. Our in vivo structural probing of 25S rRNA, using both DMS and SHAPE, revealed that the loss of the Rrp8-catalyzed m1A modification alters the conformation of domain I of yeast 25S rRNA causing translation initiation defects detectable as halfmers formation, likely because of incompetent loading of 60S on the 43S-preinitiation complex. Quantitative proteomic analysis of the yeast Δrrp8 mutant strain using 2D-DIGE, revealed that loss of m1A645 impacts production of specific set of proteins involved in carbohydrate metabolism, translation and ribosome synthesis. In mouse, NML has been characterized as a metabolic disease-associated gene linked to obesity. Our findings in yeast also point to a role of Rrp8 in primary metabolism. In conclusion, the m1A modification is crucial for maintaining an optimal 60S conformation, which in turn is important for regulating the production of key metabolic enzymes.
Genome wide identification and experimental validation of Pseudomonas aeruginosa Tat substrates
Authors: Gimenez Maxime Rémi , Chandra Govind , Van Overvelt Perrine , Voulhoux Romé , Bleves Sophie , Ize Bérengère
Published: August 2018

In bacteria, the twin-arginine translocation (Tat) pathway allows the export of folded proteins through the inner membrane. Proteins targeted to this system are synthesized with N-terminal signal peptides bearing a conserved twin-arginine motif. The Tat pathway is critical for many bacterial processes including pathogenesis and virulence. However, the full set of Tat substrates is unknown in many bacteria, and the reliability ofin silicoprediction methods largely uncertain. In this work, we performed a combination ofin silicoanalysis and experimental validation to identify a core set of Tat substrates in the opportunistic pathogenPseudomonas aeruginosa.In silicoanalysis predicted 44 putative Tat signal peptides in theP. aeruginosaPA14 proteome. We developed an improved amidase-based Tat reporter assay to show that 33 of these are real Tat signal peptides. In addition,in silicoanalysis of the full translated genome revealed a Tat candidate with a missassigned start codon. We showed that it is a new periplasmic protein inP. aeruginosa. Altogether we discovered and validated 34 Tat substrates. These show little overlap withEscherichia coliTat substrates, and functional analysis points to a general role for theP. aeruginosaTat system in the colonization of environmental niches and pathogenicity.
Topical administration of EGF suppresses immune response and protects skin barrier in DNCB-induced atopic dermatitis in NC/Nga mice
Authors: Kim Young-Je , Choi Mi Ji , Bak Dong-Ho , Lee Byung Chul , Ko Eun Jung , Ahn Ga Ram , Ahn Seung Won , Kim Moo Joong , Na Jungtae , Kim Beom Joon
Published: August 2018

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by a complex, heterogeneous pathogenesis including skin barrier dysfunction, immunology, and pruritus. Although epidermal growth factor (EGF) is essential for epithelial homeostasis and wound healing, the effect of EGF on AD remains to be explored. To develop a new therapy for AD, the anti-AD potential of EGF was investigated by inducing AD-like skin lesions in NC/Nga mice using 2,4-dinitrochlorobenzene (DNCB). EGF was administrated to NC/Nga mice to evaluate its therapeutic effect on DNCB-induced AD. EGF treatment improved dermatitis score, ear thickness, epidermal hyperplasia, serum total immunoglobulin E level, and transepidermal water loss in NC/Nga mice with DNCB-induced AD. In addition, levels of skin barrier-related proteins such as filaggrin, involucrin, loricrin, occludin, and zonula occludens-1 (ZO-1) were increased by EGF treatment. These beneficial effects of EGF on AD may be mediated by EGF regulation of Th1/Th2-mediated cytokines, mast cell hyperplasia, and protease activated receptor-2 (PAR-2) and thymic stromal lymphopoietin (TSLP), which are triggers of AD. Taken together, our findings suggest that EGF may potentially protect against AD lesional skin via regulation of skin barrier function and immune response.
Isobenzofuranone derivative JVPH3, an inhibitor of L. donovani topoisomerase II, disrupts mitochondrial architecture in trypanosomatid parasites
Authors: Chowdhury Somenath Roy , Godinho Joseane Lima Prado , Vinayagam Jayaraman , Zuma Aline Araujo , Silva Sara Teixeira De Macedo , Jaisankar Parasuraman , Rodrigues Juliany Cola Fernandes , De Souza Wanderley , Majumder Hemanta K.
Published: August 2018

Kinetoplast DNA (kDNA) bearing unusual mitochondrion of trypanosomatid parasites offers a new paradigm in chemotherapy modality. Topoisomerase II of Leishmania donovani (LdTopII), a key enzyme associated with kDNA replication, is emerging as a potential drug target. However, mode of action of LdTopII targeted compounds in the parasites at sub-cellular level remains largely unknown. Previously, we reported that an isobenzofuranone derivative, namely 3,5-bis(4-chlorophenyl)-7-hydroxyisobenzofuran-1(3H)-one (JVPH3), targets LdTopII and induces apoptosis-like cell death in L. donovani. Here, we elucidate the phenotypic changes and the events occurring at sub-cellular level caused by JVPH3 in L. donovani. In addition, we have evaluated the cytotoxicity and ultrastructural alterations caused by JVPH3 in two brazilian trypanosomatid pathogens viz. L. amazonensis and Trypanosoma cruzi. Despite killing these parasites, JVPH3 caused significantly different phenotypes in L. donovani and L. amazonensis. More than 90% population of parasites showed altered morphology. Mitochondrion was a major target organelle subsequently causing kinetoplast network disorganization in Leishmania. Altered mitochondrial architecture was evident in 75–80% Leishmania population being investigated. Quantification of mitochondrial function using JC-1 fluorophore to measure a possible mitochondrial membrane depolarization further confirmed the mitochondrion as an essential target of the JVPH3 corroborating with the phenotype observed by electron microscopy. However, the impact of JVPH3 was lesser on T. cruzi than Leishmania. The molecule caused mitochondrial alteration in 40% population of the epimastigotes being investigated. To our knowledge, this is the first report to evaluate the proliferation pattern and ultrastructural alterations caused in Brazilian kinetoplastid pathogens by a synthetic LdTopII inhibitor previously established to have promising in vivo activity against Indian strain of L. donovani.
Functional near-infrared spectroscopy for monitoring macaque cerebral motor activity during voluntary movements without head fixation
Authors: Yamada Toru , Kawaguchi Hiroshi , Kato Junpei , Matsuda Keiji , Higo Noriyuki
Published: August 2018

We developed an fNIRS system for monitoring macaque cerebral motor activity during voluntary movements without head fixation. fNIRS data at 27 channels in 7.5 mm spatial interval were calibrated by simulating light propagation through the macaque cranial tissues. The subject was instructed to repeatedly (75 times) retrieve a food pellet with alternating left or right hands from a food well for each session. We detected significant increases in oxygenated hemoglobin (Hb) and decrease in deoxygenated Hb in the primary motor area (M1) contralateral to the hand used. In more rostral and ventral regions in both hemispheres, the hemodynamic similarly changed regardless of used hand. Direct feeding to the mouth eliminated activity in the hand M1 whereas that at bilateral ventral regions (mouth M1 area) remained. Statistical analyses for the hemodynamics between left/right-hand use revealed the location of each hand M1 in either hemisphere. In these regions, the maximum amplitude and time of the maximum amplitude in the hemodynamic response evoked by food retrieval were highly correlated with the time associated with food retrieval. We could assign each channel to an appropriate functional motor area, providing proof of principle for future studies involving brain damage models in freely moving macaque monkeys.
Riverbed erosion of the final 565 kilometers of the Yangtze River (Changjiang) following construction of the Three Gorges Dam
Authors: Zheng Shuwei , Xu Y. Jun , Cheng Heqin , Wang Bo , Xu Wei , Wu Shuaihu
Published: August 2018

The world’s largest hydropower dam, the Three Gorges Dam (TGD), spans the upper Yangtze River in China, creating a 660-km long and 1.1-km wide reservoir upstream. Several recent studies reported a considerable decline in sediment load of the Lowermost Yangtze River (LmYR) and a rapid erosion in the subaqueous delta of the river mouth after the closure of the TGD in 2003. However, it is unknown if the TGD construction has also affected river channel and bed formation of the LmYR. In this study, we compared bathymetric data of the last 565 kilometers of the Yangtze River’s channel between 1998 and 2013. We found severe channel erosion following the TGD closure, with local riverbed erosion up to 10 m deep. The total volume of net erosion from the 565-km channel amounted to 1.85 billion m3, an equivalent of 2.59 billion metric tons of sediment, assuming a bulk density of 1.4 t/m3for the riverbed material. The largest erosion occurred in a 100-km reach close to the Yangtze River mouth, contributing up to 73% of the total net eroded channel volume.
Behavioural patterns of electrolyte repletion in intensive care units: lessons from a large electronic dataset
Authors: Joseph Thomas T. , DiMeglio Matthew , Huffenberger Annmarie , Laudanski Krzysztof
Published: August 2018

Repletion of electrolytes often depends on provider-specific behavior and hospital policy. We examined the pattern of electrolyte repletion across several intensive care units (ICU) in a large healthcare system from 2010–2015. This included 109 723 potassium repletions, 51 833 magnesium repletions, 2 306 calcium repletions, 8 770 phosphate repletions, and 3 128 249 visit-days over 332 018 visits. Potassium, magnesium, and calcium were usually repleted within the institutional reference range. In contrast, the bulk of phosphate repletion was done with pre-repletion serum level below the reference range. The impact of repletion on post-repletion levels was significant but uniformly small. The pre-repletion serum level had a significant inverse correlation with the post-repletion level of each electrolyte. Potassium, magnesium and phosphate follow-up labs were scheduled in 9–10 hours after their repletion. In contrast, calcium was rechecked in less than 20 minutes. Routine repletion of potassium, magnesium and calcium had no effect on the incidence of tachyarrhythmias. We estimated the expense from electrolyte repletion within the reference range was approximately $1.25 million. Absent a specific clinical indication, repleting electrolytes when the serum concentration are within normative values may represent an avenue for cost savings, staff burden unload and potential reduction in frequency of complications in the ICUs.
Feasibility of autologous plasma gel for tonsil-derived stem cell therapeutics in hypoparathyroidism
Authors: Jung Soo Yeon , Kim Ha Yeong , Oh Hyun Ju , Choi Euno , Cho Min Sun , Kim Han Su
Published: August 2018

Hypoparathyroidism is a deficiency of the parathyroid hormone (PTH) in the body. We previously reported the possibility of treating it using tonsil-derived mesenchymal stem cells (TMSCs) differentiated into PTH-releasing cells. The purpose of this study was to evaluate the feasibility of using autologous plasma gel as scaffold material in treatment of hypoparathyroidism with TMSC. We obtained plasma by venous sampling of autologous blood and centrifuged and fabricated the plasma gel using a sinusoidal pattern heating machine. After we created the hypoparathyroidism animal model, we administered undifferentiated TMSCs and TMSCs differentiated into parathyroid cells at each rat dorsum by intramuscular injection with and without the plasma gel. In the plasma gel groups, intact PTH was detected from on day 21 after TMSC injection; we did not detect intact PTH in the groups that were only transplanted with TMSCs during the entire experimental period. Serum calcium was higher and phosphorous was lower in the TMSC with plasma gel groups than in the groups with TMSCs alone. We detected PTH and chromogranin A in the TMSC-plasma gel-transplanted areas on immunohistochemistry and immunofluorescence stain. Plasma gel can be considered as a cell-delivery scaffold for treating hypoparathyroidism with tonsil-derived mesenchymal stem cells.
Metabolomic changes in the mouse retina after optic nerve injury
Authors: Sato Kota , Saigusa Daisuke , Saito Ritsumi , Fujioka Amane , Nakagawa Yurika , Nishiguchi Koji M , Kokubun Taiki , Motoike Ikuko N. , Maruyama Kazuichi , Omodaka Kazuko , Shiga Yukihiro , Uruno Akira , Koshiba Seizo , Yamamoto Masayuki , Nakazawa Toru
Published: August 2018

In glaucoma, although axonal injury drives retinal ganglion cell (RGC) death, little is known about the underlying pathomechanisms. To provide new mechanistic insights and identify new biomarkers, we combined latest non-targeting metabolomics analyses to profile altered metabolites in the mouse whole retina 2, 4, and 7 days after optic nerve crush (NC). Ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry and liquid chromatography Fourier transform mass spectrometry covering wide spectrum of metabolites in combination highlighted 30 metabolites that changed its concentration after NC. The analysis displayed similar changes for purine nucleotide and glutathione as reported previously in another animal model of axonal injury and detected multiple metabolites that increased after the injury. After studying the specificity of the identified metabolites to RGCs in histological sections using imaging mass spectrometry, two metabolites, i.e., L-acetylcarnitine and phosphatidylcholine were increased not only preceding the peak of RGC death in the whole retina but also at the RGC layer (2.3-fold and 1.2-fold, respectively). These phospholipids propose novel mechanisms of RGC death and may serve as early biomarkers of axonal injury. The combinatory metabolomics analyses promise to illuminate pathomechanisms, reveal biomarkers, and allow the discovery of new therapeutic targets of glaucoma.