bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors and Outcomes of Nontuberculous Mycobacterial Disease among Rheumatoid Arthritis Patients: A Case-Control study in a TB Endemic Area
Authors: Liao Tsai-Ling , Lin Chin-Fu , Chen Yi-Ming , Liu Hung-Jen , Chen Der-Yuan
Published: July 2016

Increasing evidence indicates that the risk of nontuberculous mycobacteria (NTM) disease is elevated in patients with rheumatoid arthritis (RA). However, the risk factors and outcomes for NTM disease among RA patients remain unclear. We conducted a case-control study and estimated odds ratios (ORs) for RA patients with NTM disease according to comorbidities and anti-rheumatic medications by using conditional logistic regression. Prior tuberculosis history (adjusted OR (aOR) =5.58, p < 0.001), hypertension (aOR = 2.55, p = 0.013), diabetes mellitus (aOR = 3.31, p = 0.005), interstitial lung disease (aOR = 8.22, p < 0.001), chronic obstructive pulmonary disease (aOR = 8.59, p < 0.001) and exposure to oral corticosteroids in a dose-dependent manner (5− < 10 mg/day aOR = 2.51, Ptrend = 0.007) were associated with a significantly increased risk of NTM disease in RA patients. The predominant species causing NTM disease in RA patients was Mycobacterium intracellulare (46.0%). Most NTM isolates were resistant to the majority of the antibiotics that are currently available, which maybe caused treatment failure; hospitalization and mortality are increased. To prevent and treat NTM disease efficiently, we suggested that it is important to monitor the development of NTM disease in RA patients receiving therapy with corticosteroids, particularly in those with predisposing factors.
Modelling the sensitivity of life history traits to climate change in a temporary pool crustacean
Authors: Pinceel Tom , Vanschoenwinkel Bram , Brendonck Luc , Buschke Falko
Published: July 2016

Temporary pool inhabitants face altered inundation regimes under climate change. While their exposure to these changes has received considerable attention, few studies have investigated their sensitivity or adaptability. Here, we use zooplankton as a model to explore how decreasing hydroperiods affect extinction risks and assess whether changes in life history traits could promote persistence. For this, we construct a three-stage matrix population model parameterised with realistic life-history values for the fairy shrimp Branchipodopsis wolfi from pools with varying hydroperiods. Our results suggest that extinction risks increase drastically once the median hydroperiod drops below a critical threshold. Although changes in life-history parameters could potentially compensate for this risk, the relative importance of each trait for population growth depends on the median hydroperiod. For example, survival of dormant eggs seemed to be most important when hydroperiods were short while the survival of freshly laid eggs and adult individuals were more important in longer-lived pools. Overall, this study demonstrates that zooplankton species are sensitive to climate change and that the adaptive capacity of organisms from temporary pools with dissimilar hydrology hinges on selection of different life history traits.
Quantification of intracellular payload release from polymersome nanoparticles
Authors: Scarpa Edoardo , Bailey Joanne L. , Janeczek Agnieszka A. , Stumpf Patrick S. , Johnston Alexander H. , Oreffo Richard O. C. , Woo Yin L. , Cheong Ying C. , Evans Nicholas D. , Newman Tracey A.
Published: July 2016

Polymersome nanoparticles (PMs) are attractive candidates for spatio-temporal controlled delivery of therapeutic agents. Although many studies have addressed cellular uptake of solid nanoparticles, there is very little data available on intracellular release of molecules encapsulated in membranous carriers, such as polymersomes. Here, we addressed this by developing a quantitative assay based on the hydrophilic dye, fluorescein. Fluorescein was encapsulated stably in PMs of mean diameter 85 nm, with minimal leakage after sustained dialysis. No fluorescence was detectable from fluorescein PMs, indicating quenching. Following incubation of L929 cells with fluorescein PMs, there was a gradual increase in intracellular fluorescence, indicating PM disruption and cytosolic release of fluorescein. By combining absorbance measurements with flow cytometry, we quantified the real-time intracellular release of a fluorescein at a single-cell resolution. We found that 173 ± 38 polymersomes released their payload per cell, with significant heterogeneity in uptake, despite controlled synchronisation of cell cycle. This novel method for quantification of the release of compounds from nanoparticles provides fundamental information on cellular uptake of nanoparticle-encapsulated compounds. It also illustrates the stochastic nature of population distribution in homogeneous cell populations, a factor that must be taken into account in clinical use of this technology.
Murine matrix metalloproteinase-20 overexpression stimulates cell invasion into the enamel layer via enhanced Wnt signaling
Authors: Shin Masashi , Suzuki Maiko , Guan Xiaomu , Smith Charles E. , Bartlett John D.
Published: July 2016

Matrix metalloproteinase-20 (MMP20) is expressed by ameloblasts in developing teeth and MMP20 mutations cause enamel malformation. We established a stably transfected Tet-Off Mmp20-inducible ameloblast-lineage cell line and found that MMP20 expression promoted cell invasion. Previously, we engineered transgenic mice (Tg) that drive Mmp20 expression and showed that Mmp20+/+Tg mice had soft enamel. Here we asked if Mmp20 overexpression disrupts ameloblast function. Incisors from Mmp20+/+ mice expressing the Mmp20 Tg had a striking cell infiltrate which nearly replaced the entire enamel layer. A thin layer of enamel-like material remained over the dentin and at the outer tooth surface, but between these regions were invading fibroblasts and epithelial cells that surrounded ectopic bone-like calcifications. Mmp20+/+Tg mice had decreased enamel organ cadherin levels compared to the Mmp20 ablated and WT mice and, instead of predominantly locating adjacent to the ameloblast cell membrane, β-catenin was predominantly present within the nuclei of invading cells. Our data suggest that increased cadherin cleavage by transgenic MMP20 in the WT background releases excess β-catenin, which translocates to ameloblast nuclei to promote cell migration/invasion. Therefore, we conclude that MMP20 plays a role in normal ameloblast migration through tightly controlled Wnt signaling and that MMP20 overexpression disrupts this process.
Host protective ASP-based vaccine against the parasitic nematode Ostertagia ostertagi triggers NK cell activation and mixed IgG1-IgG2 response
Authors: González-Hernández Ana , Van Coppernolle Stefanie , Borloo Jimmy , Van Meulder Frederik , Paerewijck Oonagh , Peelaers Iris , Leclercq Georges , Claerebout Edwin , Geldhof Peter
Published: July 2016

The mucus-dwelling parasite Ostertagia ostertagi is one of the most important gastrointestinal nematodes in cattle. Our group has previously demonstrated the protective capacity of a vaccine against this parasite based on a native activation-associated secreted protein ASP1 (nASP) in combination with the saponin adjuvant QuilA. The aim of the current study was to analyse the effect of both antigen and adjuvant on the cellular and humoral vaccine-induced immune responses by comparing the native ASP to a recombinant version expressed in Pichia pastoris (pASP) and replacing QuilA by Al(OH)3. Immunization of cattle with the protective nASP+QuilA vaccine was associated with antigen-induced proliferation of natural killer (NK) cells combined with IFN-γ secretion and the induction of a mixed IgG1/IgG2 antibody response. ASP-specific activation and proliferation of NK cells was also observed in mice following the same vaccination regime. Replacing QuilA by Al(OH)3 or nASP by pASP significantly decreased the capacity of the vaccines to trigger both NK cell activation and antibody responses and failed to induce protection against a challenge infection. Reduction of the structurally anchoring disulphide bonds of the nASP completely abolished its ability to induce NK cell activation and antibody responses, highlighting the importance of protein conformation for the immunostimulatory activity.
Deciduous trees are a large and overlooked sink for snowmelt water in the boreal forest
Authors: Young-Robertson Jessica M. , Bolton W. Robert , Bhatt Uma S. , Cristóbal Jordi , Thoman Richard
Published: July 2016

The terrestrial water cycle contains large uncertainties that impact our understanding of water budgets and climate dynamics. Water storage is a key uncertainty in the boreal water budget, with tree water storage often ignored. The goal of this study is to quantify tree water content during the snowmelt and growing season periods for Alaskan and western Canadian boreal forests. Deciduous trees reached saturation between snowmelt and leaf-out, taking up 21–25% of the available snowmelt water, while coniferous trees removed <1%. We found that deciduous trees removed 17.8–20.9 billion m3 of snowmelt water, which is equivalent to 8.7–10.2% of the Yukon River’s annual discharge. Deciduous trees transpired 2–12% (0.4–2.2 billion m3) of the absorbed snowmelt water immediately after leaf-out, increasing favorable conditions for atmospheric convection, and an additional 10–30% (2.0–5.2 billion m3) between leaf-out and mid-summer. By 2100, boreal deciduous tree area is expected to increase by 1–15%, potentially resulting in an additional 0.3–3 billion m3 of snowmelt water removed from the soil per year. This study is the first to show that deciduous tree water uptake of snowmelt water represents a large but overlooked aspect of the water balance in boreal watersheds.
Circulating cell-free mature microRNAs and their target gene prediction in bovine metritis
Authors: Kasimanickam Vanmathy , Kastelic John
Published: July 2016

Uterine infections in dairy cows are common after calving, reduce fertility and cause substantial economic losses. Conventional diagnosis (based on clinical signs) and treatment can be challenging. Serum microRNA (miRNA) profiles serve as non-invasive biomarkers in several pathological conditions including inflammatory diseases. The objective was to identify differentially expressed serum miRNAs in cows with metritis and normal uterus (four cows per group), integrate miRNAs to their target genes and categorize target genes for biological processes involved in bacterial infection and inflammatory responses. Out of 84 bovine-specific, prioritized miRNAs analyzed, 30 were differentially expressed between metritis and normal cows (p ≤ 0.05, fold regulation ≥2 magnitudes). Bta-miR-15b, bta-miR-17-3p, bta-miR-16b, bta-miR-148a, bta-miR-26b, bta-miR-101 and bta-miR-29b were highly up-regulated whereas bta-miR-148b, bta-miR-199a-3p, bta-miR-122, bta-miR-200b and bta-miR-10a were highly down-regulated in cows with metritis compared to cows with normal uterus. Highly scored target genes of up-regulated and down-regulated miRNAs were categorized for various biological processes, including biological regulation, cellular process, developmental process, metabolic process, localization, multicellular organismal process, response to stimulus, immune system process, cellular components organization, apoptotic process, biological adhesion, developmental process and locomotion that are critical to combat bacterial infections and provoke inflammatory responses.
The HSA21 gene EURL/C21ORF91 controls neurogenesis within the cerebral cortex and is implicated in the pathogenesis of Down Syndrome
Authors: Li Shan Shan , Qu Zhengdong , Haas Matilda , Ngo Linh , Heo You Jeong , Kang Hyo Jung , Britto Joanne Maria , Cullen Hayley Daniella , Vanyai Hannah Kate , Tan Seong-Seng , Chan-Ling Tailoi , Gunnersen Jenny Margaret , Heng Julian Ik-Tsen
Published: July 2016

Copy number variations to chromosome 21 (HSA21) cause intellectual disability and Down Syndrome, but our understanding of the HSA21 genetic factors which contribute to fetal brain development remains incomplete. Here, we focussed on the neurodevelopmental functions for EURL (also known as C21ORF91, Refseq Gene ID:54149), a protein-coding gene at the centromeric boundary of the Down Syndrome Critical Region (DSCR) of HSA21. We report that EURL is expressed during human and mouse cerebral cortex development, and we report that alterations to EURL mRNA levels within the human brain underlie Down Syndrome. Our gene perturbation studies in mice demonstrate that disruptions to Eurl impair progenitor proliferation and neuronal differentiation. Also, we find that disruptions to Eurl impair the long-term positioning and dendritic spine densities of cortical projection neurons. We provide evidence that EURL interacts with the coiled-coil domain-containing protein CCDC85B so as to modulate β-catenin levels in cells. Further, we utilised a fluorescent reporter (8xTOPFLASHd2EGFP) to demonstrate that disruptions to Eurl alter β-catenin signalling in vitro as well as in vivo. Together, these studies highlight EURL as an important new player in neuronal development that is likely to impact on the neuropathogenesis of HSA21-related disorders including Down Syndrome.
Delineation of autoantibody repertoire through differential proteogenomics in hepatitis C virus-induced cryoglobulinemia
Authors: Ogishi Masato , Yotsuyanagi Hiroshi , Moriya Kyoji , Koike Kazuhiko
Published: July 2016

Antibodies cross-reactive to pathogens and autoantigens are considered pivotal in both infection control and accompanying autoimmunity. However, the pathogenic roles of autoantibodies largely remain elusive without a priori knowledge of disease-specific autoantigens. Here, through a novel quantitative proteogenomics approach, we demonstrated a successful identification of immunoglobulin variable heavy chain (VH) sequences highly enriched in pathological immune complex from clinical specimens obtained from a patient with hepatitis C virus-induced cryoglobulinemia (HCV-CG). Reconstructed single-domain antibodies were reactive to both HCV antigens and potentially liver-derived human proteins. Moreover, over the course of antiviral therapy, a substantial “de-evolution” of a distinct sub-repertoire was discovered, to which proteomically identified cryoprecipitation-prone autoantibodies belonged. This sub-repertoire was characterized by IGHJ6*03-derived, long, hydrophobic complementarity determining region (CDR-H3). This study provides a proof-of-concept of de novo mining of autoantibodies and corresponding autoantigen candidates in a disease-specific context in human, thus facilitating future reverse-translational research for the discovery of novel biomarkers and the development of antigen-specific immunotherapy against various autoantibody-related disorders.
X-ray detection with zinc-blende (cubic) GaN Schottky diodes
Authors: Gohil T. , Whale J. , Lioliou G. , Novikov S. V. , Foxon C. T. , Kent A. J. , Barnett A. M.
Published: July 2016

The room temperature X-ray responses as functions of time of two n type cubic GaN Schottky diodes (200 μm and 400 μm diameters) are reported. The current densities as functions of time for both diodes showed fast turn-on transients and increases in current density when illuminated with X-ray photons of energy up to 35 keV. The diodes were also electrically characterized: capacitance, implied depletion width and dark current measurements as functions of applied bias at room temperature are presented. At −5 V reverse bias, the capacitances of the diodes were measured to be (84.05 ± 0.01) pF and (121.67 ± 0.02) pF, respectively. At −5 V reverse bias, the dark current densities of the diodes were measured to be (347.2 ± 0.4) mA cm−2 and (189.0 ± 0.2) mA cm−2, respectively. The Schottky barrier heights of the devices (0.52 ± 0.07) eV and (0.63 ± 0.09) eV, respectively, were extracted from the forward dark current characteristics.
Viral Evolution and Cytotoxic T Cell Restricted Selection in Acute Infant HIV-1 Infection
Authors: Garcia-Knight Miguel A. , Slyker Jennifer , Payne Barbara Lohman , Pond Sergei L. Kosakovsky , de Silva Thushan I. , Chohan Bhavna , Khasimwa Brian , Mbori-Ngacha Dorothy , John-Stewart Grace , Rowland-Jones Sarah L. , Esbjörnsson Joakim
Published: July 2016

Antiretroviral therapy-naive HIV-1 infected infants experience poor viral containment and rapid disease progression compared to adults. Viral factors (e.g. transmitted cytotoxic T- lymphocyte (CTL) escape mutations) or infant factors (e.g. reduced CTL functional capacity) may explain this observation. We assessed CTL functionality by analysing selection in CTL-targeted HIV-1 epitopes following perinatal infection. HIV-1 gag, pol and nef sequences were generated from a historical repository of longitudinal specimens from 19 vertically infected infants. Evolutionary rate and selection were estimated for each gene and in CTL-restricted and non-restricted epitopes. Evolutionary rate was higher in nef and gag vs. pol, and lower in infants with non-severe immunosuppression vs. severe immunosuppression across gag and nef. Selection pressure was stronger in infants with non-severe immunosuppression vs. severe immunosuppression across gag. The analysis also showed that infants with non-severe immunosuppression had stronger selection in CTL-restricted vs. non-restricted epitopes in gag and nef. Evidence of stronger CTL selection was absent in infants with severe immunosuppression. These data indicate that infant CTLs can exert selection pressure on gag and nef epitopes in early infection and that stronger selection across CTL epitopes is associated with favourable clinical outcomes. These results have implications for the development of paediatric HIV-1 vaccines.
Decadal variability of tropical tropopause temperature and its relationship to the Pacific Decadal Oscillation
Authors: Wang Wuke , Matthes Katja , Omrani Nour-Eddine , Latif Mojib
Published: July 2016

Tropopause temperatures (TPTs) control the amount of stratospheric water vapour, which influences chemistry, radiation and circulation in the stratosphere and is also an important driver of surface climate. Decadal variability and long-term trends in tropical TPTs as well as stratospheric water vapour are largely unknown. Here, we present for the first time evidence, from reanalysis and state-of-the-art climate model simulations, of a link between decadal variability in tropical TPTs and the Pacific Decadal Oscillation (PDO). The negative phase of the PDO is associated with anomalously cold sea surface temperatures (SSTs) in the tropical east and central Pacific, which enhance the zonal SST gradient across the equatorial Pacific. The latter drives a stronger Walker Circulation and a weaker Hadley Circulation, which leads to less convection and subsequently a warmer tropopause over the central equatorial Pacific. Over the North Pacific, positive sea level pressure anomalies occur, which damp vertical wave propagation into the stratosphere. This in turn slows the Brewer-Dobson circulation and hence warms the tropical tropopause, enabling more water vapour to enter the stratosphere. The reverse chain of events holds for the positive phase of the PDO. Such ocean-troposphere-stratosphere interactions may provide an important feedback on the Earth’s global surface temperature.
CREB-mediated synaptogenesis and neurogenesis is crucial for the role of 5-HT1a receptors in modulating anxiety behaviors
Authors: Zhang Jing , Cai Cheng-Yun , Wu Hai-Yin , Zhu Li-Juan , Luo Chun-Xia , Zhu Dong-Ya
Published: July 2016

Serotonin 1a-receptor (5-HT1aR) has been specifically implicated in the pathogenesis of anxiety. However, the mechanism underlying the role of 5-HT1aR in anxiety remains poorly understood. Here we show in mice that the transcription factor cAMP response element binding protein (CREB) in the hippocampus functions as an effector of 5-HT1aR in modulating anxiety-related behaviors. We generated recombinant lentivirus LV-CREB133-GFP expressing a dominant negative CREB which could not be phosphorylated at Ser133 to specifically reduce CREB activity, and LV-VP16-CREB-GFP expressing a constitutively active fusion protein VP16-CREB which could be phosphorylated by itself to specifically enhance CREB activity. LV-CREB133-GFP neutralized 5-HT1aR agonist-induced up-regulation of synapse density, spine density, dendrite complexity, neurogenesis, and the expression of synapsin and spinophilin, two well-characterized synaptic proteins, and abolished the anxiolytic effect of 5-HT1aR agonist; whereas LV-VP16-CREB-GFP rescued the 5-HT1aR antagonist-induced down-regulation of synapse density, spine density, dendrite complexity, neurogenesis and synapsin and spinophilin expression, and reversed the anxiogenic effect of 5-HT1aR antagonist. The deletion of neurogenesis by irradiation or the diminution of synaptogenesis by knockdown of synapsin expression abolished the anxiolytic effects of both CREB and 5-HT1aR activation. These findings suggest that CREB-mediated hippoacampus structural plasticity is crucial for the role of 5-HT1aR in modulating anxiety-related behaviors.
Joint effects of folate intake and one-carbon-metabolizing genetic polymorphisms on breast cancer risk: a case-control study in China
Authors: Luo Wei-Ping , Li Bin , Lin Fang-Yu , Yan Bo , Du Yu-Feng , Mo Xiong-Fei , Wang Lian , Zhang Cai-Xia
Published: July 2016

This study aimed to examine the joint effects of folate intake, polymorphisms of 5,10- methylenetetrahydrofolate reductase (MTHFR), methionine synthesis reductase (MTRR) and methionine synthase (MTR) genes and breast cancer risk. A case-control study of 570 consecutively recruited breast cancer cases and 576 controls was conducted in Guangzhou, China. Multifactor dimensionality reduction and logistic regression approach were used to evaluate gene-gene interaction. The covariates were chosen based on comparison of baseline characteristics of cases and controls. Folate intake was found to be inversely associated with breast cancer risk. The MTRRrs162036 GG genotype was associated with a decreased risk of breast cancer [adjusted odds ratio (OR) 0.41, 95% confidence interval (CI) 0.20–0.85]. Compared with the wild-type group (MTRRrs162036 AA with MTRrs1805087 AA) MTRRrs162036 AA with MTRrs1805087 GA + GG was associated with a decreased risk (OR 0.70, 95% CI 0.48–1.03). With the combined MTHFRrs1801131 TT and MTHFRrs1801133 GG genotypes as a reference, MTHFRrs1801131 TT with MTHFRrs1801133 GA + AA was associated with a decreased risk (OR 0.78, 95% CI 0.57 – 1.08) and MTHFRrs1801131 GT + GG with MTHFRrs1801133 GA + AA was associated with an increased risk (OR 1.35, 95% CI 0.88–2.05). The joint impact of MTRRrs162036 and MTRrs1805087, MTHFRrs1801131 and MTHFRrs1801133, folate and MTHFRrs1801133 may contribute to breast cancer risk.
Reproduction of the long-spined sea urchin Diadema setosum in the Gulf of Aqaba - implications for the use of gonad-indexes
Authors: Bronstein Omri , Kroh Andreas , Loya Yossi
Published: July 2016

As global warming and climate-change proceeds ever more rapidly, organisms depending on seasonal cues to synchronize reproduction face an unclear future. Reproduction in Diadema setosum in the Gulf of Aqaba (Red Sea) is seasonal, with mature individuals occurring from July to October. Gonad indexes (GI), in contrast, indicate that spawning occurs from August through December and suggests two main spawning events. Histological analysis, however, indicate that the second peak of GI values cannot be related to spawning, but rather correspond to recovering individuals. In Diadema, examination of GI values alone may thus lead to erroneous conclusions. GI was moderately-strong positively correlated with sea-surface temperatures, but not with chlorophyll-a concentrations or photoperiod. Spawning coincides with the onset of the annual chlorophyll-a increase, however, which might be advantageous for nutrition of the developing larvae. First significant GI increase coincides with the shortening of day-length, which may act as a cue for D. setosum gametogenesis. Gametogenesis is highly synchronised between sexes, although the mature phase of females exceeds that of males. The non-complete overlap may represent sampling bias or represent an adaptive strategy for enhancing fertilisation success. Skewed sex ratios (♀:♂ 1:0.59, n = 360) in the Gulf of Aqaba may be related to pollution.
Otosclerosis Associated with a De Novo Mutation −832G > A in the TGFB1 Gene Promoter Causing a Decreased Expression Level
Authors: Priyadarshi Saurabh , Hansdah Kirtal , Ray Chinmay Sundar , Biswal Narayan Chandra , Ramchander Puppala Venkat
Published: July 2016

Otosclerosis (OTSC) is defined by abnormal bone remodeling in the otic capsule of middle ear which leads to conductive hearing loss. In our previous study, we have identified a de novo heterozygous mutation −832G > A in the promoter of TGFB1 in an otosclerosis patient. In the present study, we progressively screened this mutation in a cohort of 254 cases and 262 controls. The family members of the patient positive for −832G > A variation were also screened and found inheritance of this variation only to her daughter. Interestingly, this variation is associated with a decreased level of the TGFB1 transcript in the patient compared to her parents and controls. In silico analysis of this mutation predicted the altered binding of two transcription factors v-Myb and MZF1 in the mutated promoter sequence. Further, functional analysis of this mutation using in vitro luciferase and electrophoretic mobility shift assays revealed that this variation is associated with decreased gene expression. In conclusion, this study established the fact that TGFB1 mutation −832G > A altered the TGFB1 promoter activity, which could affect the susceptibility to otosclerosis development. Further, systemic analysis of TGFB1 gene sequence and expression analysis of this gene might reveal its precise role in the pathogenesis of otosclerosis.
An essential role of SVZ progenitors in cortical folding in gyrencephalic mammals
Authors: Toda Tomohisa , Shinmyo Yohei , Dinh Duong Tung Anh , Masuda Kosuke , Kawasaki Hiroshi
Published: July 2016

Because folding of the cerebral cortex in the mammalian brain is believed to be crucial for higher brain functions, the mechanisms underlying its formation during development and evolution are of great interest. Although it has been proposed that increased neural progenitors in the subventricular zone (SVZ) are responsible for making cortical folds, their roles in cortical folding are still largely unclear, mainly because genetic methods for gyrencephalic mammals had been poorly available. Here, by taking an advantage of our newly developed in utero electroporation technique for the gyrencephalic brain of ferrets, we investigated the role of SVZ progenitors in cortical folding. We found regional differences in the abundance of SVZ progenitors in the developing ferret brain even before cortical folds began to be formed. When Tbr2 transcription factor was inhibited, intermediate progenitor cells were markedly reduced in the ferret cerebral cortex. Interestingly, outer radial glial cells were also reduced by inhibiting Tbr2. We uncovered that reduced numbers of SVZ progenitors resulted in impaired cortical folding. When Tbr2 was inhibited, upper cortical layers were preferentially reduced in gyri compared to those in sulci. Our findings indicate the biological importance of SVZ progenitors in cortical folding in the gyrencephalic brain.
The vicinity of hyper-honeycomb β-Li2IrO3 to a three-dimensional Kitaev spin liquid state
Authors: Katukuri Vamshi M. , Yadav Ravi , Hozoi Liviu , Nishimoto Satoshi , van den Brink Jeroen
Published: July 2016

Due to the combination of a substantial spin-orbit coupling and correlation effects, iridium oxides hold a prominent place in the search for novel quantum states of matter, including, e.g., Kitaev spin liquids and topological Weyl states. We establish the promise of the very recently synthesized hyper-honeycomb iridate β-Li2IrO3 in this regard. A detailed theoretical analysis reveals the presence of large ferromagnetic first-neighbor Kitaev interactions, while a second-neighbor antiferromagnetic Heisenberg exchange drives the ground state from ferro to zigzag order via a three-dimensional Kitaev spin liquid and an incommensurate phase. Experiment puts the system in the latter regime but the Kitaev spin liquid is very close and reachable by a slight modification of the ratio between the second- and first-neighbor couplings, for instance via strain.
Onionin A inhibits ovarian cancer progression by suppressing cancer cell proliferation and the protumour function of macrophages
Authors: Tsuboki Junko , Fujiwara Yukio , Horlad Hasita , Shiraishi Daisuke , Nohara Toshihiro , Tayama Shingo , Motohara Takeshi , Saito Yoichi , Ikeda Tsuyoshi , Takaishi Kiyomi , Tashiro Hironori , Yonemoto Yukihiro , Katabuchi Hidetaka , Takeya Motohiro , Komohara Yoshihiro
Published: July 2016

It is well known that tumour-associated macrophages (TAMs) play an important role in tumour development by modulating the tumour microenvironment, and targeting of protumour activation or the M2 polarization of TAMs is expected to be an effective therapy for cancer patients. We previously demonstrated that onionin A (ONA), a natural low molecular weight compound isolated from onions, has an inhibitory effect on M2 macrophage polarization. In the present study, we investigated whether ONA had a therapeutic anti-ovarian cancer effect using in vitro and in vivo studies. We found that ONA reduced the extent of ovarian cancer cell proliferation induced by co-culture with human macrophages. In addition, we also found that ONA directly suppressed cancer cell proliferation. A combinatorial effect with ONA and anti-cancer drugs was also observed. The activation of signal transducer and activator of transcription 3 (STAT3), which is involved in cell proliferation and chemo-resistance, was significantly abrogated by ONA in ovarian cancer cells. Furthermore, the administration of ONA suppressed cancer progression and prolonged the survival time in a murine ovarian cancer model under single and combined treatment conditions. Thus, ONA is considered useful for the additional treatment of patients with ovarian cancer owing to its suppression of the protumour activation of TAMs and direct cytotoxicity against cancer cells.
In Situ Spectral Kinetics of Cr(VI) Reduction by c-Type Cytochromes in A Suspension of Living Shewanella putrefaciens 200
Authors: Liu Tongxu , Li Xiaomin , Li Fangbai , Han Rui , Wu Yundang , Yuan Xiu , Wang Ying
Published: July 2016

Although c-type cytochromes (c-Cyts) mediating metal reduction have been mainly investigated with in vitro purified proteins of dissimilatory metal reducing bacteria, the in vivo behavior of c-Cyts is still unclear given the difficulty in measuring the proteins of intact cells. Here, c-Cyts in living Shewanella putrefaciens 200 (SP200) was successfully quantified using diffuse-transmission UV/Vis spectroscopy due to the strong absorbance of hemes, and the in situ spectral kinetics of Cr(VI) reduction by c-Cyts were examined over time. The reduced product Cr(III) observed on the cell surface may play a role in inhibiting the Cr(VI) reduction and reducing the cell numbers with high concentrations (>200 μM) of Cr(VI) evidenced by the 16S rRNA analysis. A brief kinetic model was established with two predominant reactions, redox transformation of c-Cyts and Cr(VI) reduction by reduced c-Cyts, but the fitting curves were not well-matched with c-Cyts data. The Cr(III)-induced inhibitory effect to the cellular function of redox transformation of c-Cyts was then added to the model, resulting in substantially improved the model fitting. This study provides a case of directly examining the reaction properties of outer-membrane enzyme during microbial metal reduction processes under physiological conditions.
Continuous leaky-wave scanning using periodically modulated spoof plasmonic waveguide
Authors: Kong Gu Sheng , Ma Hui Feng , Cai Ben Geng , Cui Tie Jun
Published: July 2016

The plasmonic waveguide made of uniform corrugated metallic strip can support and guide spoof surface plasmon polaritons (SSPPs) with high confinements. Here, we propose periodically-modulated plasmonic waveguide composed of non-uniform corrugated metallic strip to convert SSPPs to radiating waves, in which the main beam of radiations can steer continuously as the frequency changes. To increase the radiation efficiency of the periodically-modulated plasmonic waveguide at the broadside, an asymmetrical plasmonic waveguide is further presented to reduce the reflections and realize continuous leaky-wave scanning. Both numerical simulations and experimental results show that the radiation efficiency can be improved greatly and the main beam of leaky-wave radiations can steer from the backward quadrant to the forward quadrant, passing through the broadside direction, which generally is difficult to be realized by the common leaky-wave antennas.
Nanoparticle-Mediated Delivery of Irbesartan Induces Cardioprotection from Myocardial Ischemia-Reperfusion Injury by Antagonizing Monocyte-Mediated Inflammation
Authors: Nakano Yasuhiro , Matoba Tetsuya , Tokutome Masaki , Funamoto Daiki , Katsuki Shunsuke , Ikeda Gentaro , Nagaoka Kazuhiro , Ishikita Ayako , Nakano Kaku , Koga Jun-ichiro , Sunagawa Kenji , Egashira Kensuke
Published: July 2016

Myocardial ischemia-reperfusion (IR) injury limits the therapeutic effect of early reperfusion therapy for acute myocardial infarction (AMI), in which the recruitment of inflammatory monocytes plays a causative role. Here we develop bioabsorbable poly-lactic/glycolic acid (PLGA) nanoparticles incorporating irbesartan, an angiotensin II type 1 receptor blocker with a peroxisome proliferator-activated receptor (PPAR)γ agonistic effect (irbesartan-NP). In a mouse model of IR injury, intravenous PLGA nanoparticles distribute to the IR myocardium and monocytes in the blood and in the IR heart. Single intravenous treatment at the time of reperfusion with irbesartan-NP (3.0 mg kg−1 irbesartan), but not with control nanoparticles or irbesartan solution (3.0 mg kg−1), inhibits the recruitment of inflammatory monocytes to the IR heart and reduces the infarct size via PPARγ-dependent anti-inflammatory mechanisms and ameliorates left ventricular remodeling 21 days after IR. Irbesartan-NP is a novel approach to treat myocardial IR injury in patients with AMI.
Decreased expression of Calpain-9 predicts unfavorable prognosis in patients with gastric cancer
Authors: Peng Peike , Wu Weicheng , Zhao Junjie , Song Shushu , Wang Xuefei , Jia Dongwei , Shao Miaomiao , Zhang Mingming , Li Lili , Wang Lan , Duan Fangfang , Zhao Ran , Yang Caiting , Wu Hao , Zhang Jie , Shen Zhenbin , Ruan Yuanyuan , Gu Jianxin
Published: July 2016

Calpain-8 and calpain-9 belong to the family of calcium-dependent cysteine proteases, which are highly expressed in the stomach. However, the roles of calpain-8 and calpain-9 in gastric tumorigenesis remain little understood. Herein, we demonstrated that calpain-9 was generally decreased in gastric cancer cell lines and primary tumor tissues, while calpain-8 expression was not significantly altered. Calpain-9, but not calpain-8, induced cell cycle arrest in the G1 phase and cellular apoptosis in vitro, and it attenuated the growth of subcutaneous tumor xenografts in vivo. Low expression of calpain-9 was positively associated with male sex, late T stage, lymph node metastasis, and advanced TNM stage. Further analysis identified calpain-9 as an independent prognostic factor for poor prognosis, and combining calpain-9 with TNM stage generated a better predictive model for patient outcomes. In conclusion, calpain-9 is a tumor suppressor that can be regarded as a potential prognosis indicator for clinical outcomes in gastric cancer.
Vegetation change impacts on soil organic carbon chemical composition in subtropical forests
Authors: Guo Xiaoping , Meng Miaojing , Zhang Jinchi , Chen Han Y. H.
Published: July 2016

Changes in the chemical composition of soil organic carbon (SOC) might strongly affect the global carbon cycle as it controls the SOC decomposition rate. Vegetation change associated with long-term land use changes is known to strongly impact the chemical composition of SOC; however, data on the impacts of vegetation change following disturbance events of short durations and succession that occur frequently in forest ecosystems via diverse management objectives on SOC chemical composition are negligible. Here we examined the impacts of vegetation changes on the chemical composition of SOC by sampling soils of native broad-leaved forests, planted mixed broad-leaved and coniferous forests and tea gardens in eastern China. We used nuclear magnetic resonance spectroscopy to quantify SOC chemical composition. We found that among all components of SOC chemical composition, alkyl carbon (C) and aryl C were more liable to change with vegetation than other SOC components. Soil pH was negatively correlated to the relative abundances of alkyl C and N-alkyl C and Shannon’s index of overstory plant species was positively correlated to the relative abundances of phenolic C and aromaticity. Our results suggest that vegetation changes following short disturbance events and succession may strongly alter SOC chemical composition in forest ecosystems.
Strong and Anomalous Thermal Expansion Precedes the Thermosalient Effect in Dynamic Molecular Crystals
Authors: Panda Manas K. , Centore Roberto , Causà Mauro , Tuzi Angela , Borbone Fabio , Naumov Panče
Published: July 2016

The ability of thermosalient solids, organic analogues of inorganic martensites, to move by rapid mechanical reconfiguration or ballistic event remains visually appealing and potentially useful, yet mechanistically elusive phenomenon. Here, with a material that undergoes both thermosalient and non-thermosalient phase transitions, we demonstrate that the thermosalient effect is preceded by anomalous thermal expansion of the unit cell. The crystal explosion occurs as sudden release of the latent strain accumulated during the anisotropic, exceedingly strong expansion of the unit cell with αa = 225.9 × 10−6 K−1, αb = 238.8 × 10−6 K−1 and αc = −290.0 × 10−6 K−1, the latter being the largest negative thermal expansivity observed for an organic compound thus far. The results point out to the occurence of the thermosalient effect in phase transitions as means to identify new molecular materials with strong positive and/or negative thermal expansion which prior to this work could only be discovered serendipitously.
Non-responsiveness to intravitreal aflibercept treatment in neovascular age-related macular degeneration: implications of serous pigment epithelial detachment
Authors: Nagai Norihiro , Suzuki Misa , Uchida Atsuro , Kurihara Toshihide , Kamoshita Mamoru , Minami Sakiko , Shinoda Hajime , Tsubota Kazuo , Ozawa Yoko
Published: July 2016

The prognosis of neovascular age-related macular degeneration (AMD) has been improved by anti-vascular endothelial growth factor treatments, including intravitreal aflibercept (IVA) treatment. However, many patients remain incurable. In this study, we retrospectively evaluated non-responsiveness to IVA monotherapy at 12 months in 133 eyes of 133 AMD patients. Sixty-two patients were initially treatment-naive, and 71 had received other treatments before IVA (the treatment-switched group). Mean best-corrected visual acuity (BCVA) was improved in the treatment-naive group but not in the treatment-switched group, although mean central retinal thickness (CRT) decreased in both groups. The respective percentages of non-responders as determined by worsened BCVA in the treatment-naive and treatment-switched groups were 8.1% and 15.5%, and via fundus findings, they were 12.9% and 8.5%. Multivariate analyses adjusted for age, gender, CRT, and greatest linear dimension showed that serous pigment epithelial detachment (PED) at baseline was associated with non-responsiveness in both groups as determined by BCVA and by fundus findings, and fibrovascular PED measurements indicated no response as determined by fundus findings in the treatment-switched group. The results reported herein may assist the formulation of appropriate treatment protocols for AMD patients.
Electronic Conduction in Ti/Poly-TiO2/Ti Structures
Authors: Hossein-Babaei Faramarz , Alaei-Sheini Navid
Published: July 2016

Recent intensive investigations on metal/metal oxide/metal structures have targeted nanometric single grain oxides at high electric fields. Similar research on thicker polycrystalline oxide layers can bridge the results to the prior literature on varistors and may uncover novel ionic/electronic features originating from the conduction mechanisms involving grain boundaries. Here, we investigate electronic conduction in Ti/poly-TiO2−x/Ti structures with different oxygen vacancy distributions and describe the observed features based on the motion and rearrangement of the ionized oxygen vacancies (IOVs) on the grain facets rather than the grain interiors. Containing no interface energy barrier, Ti/poly-TiO2/Ti devices demonstrate high resistance ohmic conduction at biasing fields below 5 × 106 V.m−1; higher fields drive the samples to a distinctly nonlinear and hysteretic low resistance status. The observed threshold is two orders of magnitude smaller than the typical resistance switching fields reported for the nanosized single grain memristors. This is consistent with the smaller activation energies reported for the IOV motion on the rutile facets than its interior. The presented model describes the observed dependence of the threshold field on the relative humidity of the surrounding air based on the lower activation energies reported for the hydroxyl-assisted IOV motion on the rutile facets.
Novel Self-shrinking Mask for Sub-3 nm Pattern Fabrication
Authors: Yang Po-Shuan , Cheng Po-Hsien , Kao C. Robert , Chen Miin-Jang
Published: July 2016

It is very difficult to realize sub-3 nm patterns using conventional lithography for next-generation high-performance nanosensing, photonic and computing devices. Here we propose a completely original and novel concept, termed self-shrinking dielectric mask (SDM), to fabricate sub-3 nm patterns. Instead of focusing the electron and ion beams or light to an extreme scale, the SDM method relies on a hard dielectric mask which shrinks the critical dimension of nanopatterns during the ion irradiation. Based on the SDM method, a linewidth as low as 2.1 nm was achieved along with a high aspect ratio in the sub-10 nm scale. In addition, numerous patterns with assorted shapes can be fabricated simultaneously using the SDM technique, exhibiting a much higher throughput than conventional ion beam lithography. Therefore, the SDM method can be widely applied in the fields which need extreme nanoscale fabrication.
The role of dimensionality in neuronal network dynamics
Authors: Ulloa Severino Francesco Paolo , Ban Jelena , Song Qin , Tang Mingliang , Bianconi Ginestra , Cheng Guosheng , Torre Vincent
Published: July 2016

Recent results from network theory show that complexity affects several dynamical properties of networks that favor synchronization. Here we show that synchronization in 2D and 3D neuronal networks is significantly different. Using dissociated hippocampal neurons we compared properties of cultures grown on a flat 2D substrates with those formed on 3D graphene foam scaffolds. Both 2D and 3D cultures had comparable glia to neuron ratio and the percentage of GABAergic inhibitory neurons. 3D cultures because of their dimension have many connections among distant neurons leading to small-world networks and their characteristic dynamics. After one week, calcium imaging revealed moderately synchronous activity in 2D networks, but the degree of synchrony of 3D networks was higher and had two regimes: a highly synchronized (HS) and a moderately synchronized (MS) regime. The HS regime was never observed in 2D networks. During the MS regime, neuronal assemblies in synchrony changed with time as observed in mammalian brains. After two weeks, the degree of synchrony in 3D networks decreased, as observed in vivo. These results show that dimensionality determines properties of neuronal networks and that several features of brain dynamics are a consequence of its 3D topology.
Mechanism for insulin-like peptide 5 distinguishing the homologous relaxin family peptide receptor 3 and 4
Authors: Hu Meng-Jun , Shao Xiao-Xia , Wang Jia-Hui , Wei Dian , Guo Yu-Qi , Liu Ya-Li , Xu Zeng-Guang , Guo Zhan-Yun
Published: July 2016

The relaxin family peptides play a variety of biological functions by activating four G protein-coupled receptors, RXFP1–4. Among them, insulin-like peptide 5 (INSL5) and relaxin-3 share the highest sequence homology, but they have distinct receptor preference: INSL5 can activate RXFP4 only, while relaxin-3 can activate RXFP3, RXFP4 and RXFP1. Previous studies suggest that the A-chain is responsible for their different selectivity for RXFP1. However, the mechanism by which INSL5 distinguishes the homologous RXFP4 and RXFP3 remains unknown. In the present work, we chemically evolved INSL5 in vitro to a strong agonist of both RXFP4 and RXFP3 through replacement of its five B-chain residues with the corresponding residues of relaxin-3. We identified four determinants (B2Glu, B9Leu, B17Tyr and a rigid B-chain C-terminus) on INSL5 that are responsible for its inactivity at RXFP3. In reverse experiments, we grafted these determinants onto a chimeric R3/I5 peptide, which contains the B-chain of relaxin-3 and the A-chain of INSL5 and retains full activation potency at RXFP3 and RXFP4. All resultant R3/I5 mutants retained high activation potency towards RXFP4, but most displayed significantly decreased or even abolished activation potency towards RXFP3, confirming the role of these four INSL5 determinants in distinguishing RXFP4 from RXFP3.
Atomic structure and oxygen deficiency of the ultrathin aluminium oxide barrier in Al/AlOx/Al Josephson junctions
Authors: Zeng Lunjie , Tran Dung Trung , Tai Cheuk-Wai , Svensson Gunnar , Olsson Eva
Published: July 2016

Al/AlOx/Al Josephson junctions are the building blocks of a wide range of superconducting quantum devices that are key elements for quantum computers, extremely sensitive magnetometers and radiation detectors. The properties of the junctions and the superconducting quantum devices are determined by the atomic structure of the tunnel barrier. The nanoscale dimension and disordered nature of the barrier oxide have been challenges for the direct experimental investigation of the atomic structure of the tunnel barrier. Here we show that the miniaturized dimension of the barrier and the interfacial interaction between crystalline Al and amorphous AlOx give rise to oxygen deficiency at the metal/oxide interfaces. In the interior of the barrier, the oxide resembles the atomic structure of bulk aluminium oxide. Atomic defects such as oxygen vacancies at the interfaces can be the origin of the two-level systems and contribute to decoherence and noise in superconducting quantum circuits.