bluuebunny/crossref_metadata_2025 huggingface dataset:
An evolving view of retinogeniculate transmission
Authors: LITVINA ELIZABETH Y. , CHEN CHINFEI
Published: August 2017

The thalamocortical (TC) relay neuron of the dorsoLateral Geniculate Nucleus (dLGN) has borne its imprecise label for many decades in spite of strong evidence that its role in visual processing transcends the implied simplicity of the term “relay”. The retinogeniculate synapse is the site of communication between a retinal ganglion cell and a TC neuron of the dLGN. Activation of retinal fibers in the optic tract causes reliable, rapid, and robust postsynaptic potentials that drive postsynaptics spikes in a TC neuron. Cortical and subcortical modulatory systems have been known for decades to regulate retinogeniculate transmission. The dynamic properties that the retinogeniculate synapse itself exhibits during and after developmental refinement further enrich the role of the dLGN in the transmission of the retinal signal. Here we consider the structural and functional substrates for retinogeniculate synaptic transmission and plasticity, and reflect on how the complexity of the retinogeniculate synapse imparts a novel dynamic and influential capacity to subcortical processing of visual information.
From Gospel to Law: The Lutheran Reformation and Its Impact on Legal Culture
Authors: Witte John
Published: August 2017

The Lutheran Reformation transformed not only theology and the Church but also law and the State. Despite his early rebuke of law in favour of the gospel, Martin Luther eventually joined up with various jurists and political leaders to craft ambitious legal reforms of Church, State and society on the strength of his new theology, particularly his new two-kingdoms theory. These legal reforms were defined and defended in hundreds of monographs, pamphlets and sermons published by Lutheran writers from the 1520s onwards. They were refined and routinised in equally large numbers of new Reformation ordinances that brought fundamental changes to theology and law, Church and State, marriage and family, criminal law and procedure, and education and charity. Critics have long treated this legal phase of the Reformation as a corruption of Luther's original message of Christian freedom from the strictures of all human laws and traditions. But Luther ultimately realised that he needed the law to stabilise and enforce the new Protestant teachings. Radical theological reforms had made possible fundamental legal reforms, which, in turn, would make those theological reforms palpable. In the course of the 1530s and thereafter, the Lutheran Reformation became in its essence both a theological and a legal reform movement. It struck new balances between law and gospel, rule and equity, order and faith, and structure and spirit.
February–May 2017
Authors: Cranmer Frank
Published: August 2017

The EU (Notification of Withdrawal) Bill completed its passage through Parliament and received Royal Assent on 16 March. On 29 March, the United Kingdom's Ambassador to the European Union, Tim Barrow, handed over the Prime Minister's formal letter of notification under Article 50 of the Treaty on the European Union to the President of the European Council, thereby triggering the withdrawal process. Inevitably, however, the period since the last report was dominated not so much by Brexit as by the unexpected General Election.
Smartphone tool to collect repeated 24 h dietary recall data in Nepal
Authors: Harris-Fry Helen , Beard B James , Harrisson Tom , Paudel Puskar , Shrestha Niva , Jha Sonali , Shrestha Bhim P , Manandhar Dharma S , Costello Anthony , Saville Naomi M
Published: August 2017

Objective

To outline the development of a smartphone-based tool to collect thrice-repeated 24 h dietary recall data in rural Nepal, and to describe energy intakes, common errors and researchers’ experiences using the tool.

Design

We designed a novel tool to collect multi-pass 24 h dietary recalls in rural Nepal by combining the use of a CommCare questionnaire on smartphones, a paper form, a QR (quick response)-coded list of foods and a photographic atlas of portion sizes. Twenty interviewers collected dietary data on three non-consecutive days per respondent, with three respondents per household. Intakes were converted into nutrients using databases on nutritional composition of foods, recipes and portion sizes.

Setting

Dhanusha and Mahottari districts, Nepal.

Subjects

Pregnant women, their mothers-in-law and male household heads. Energy intakes assessed in 150 households; data corrections and our experiences reported from 805 households and 6765 individual recalls.

Results

Dietary intake estimates gave plausible values, with male household heads appearing to have higher energy intakes (median (25th–75th centile): 12 079 (9293–14 108) kJ/d) than female members (8979 (7234–11 042) kJ/d for pregnant women). Manual editing of data was required when interviewers mistook portions for food codes and for coding items not on the food list. Smartphones enabled quick monitoring of data and interviewer performance, but we initially faced technical challenges with CommCare forms crashing.

Conclusions

With sufficient time dedicated to development and pre-testing, this novel smartphone-based tool provides a useful method to collect data. Future work is needed to further validate this tool and adapt it for other contexts.
Greater access to healthy food outlets in the home and school environment is associated with better dietary quality in young children
Authors: Barrett Millie , Crozier Sarah , Lewis Daniel , Godfrey Keith , Robinson Sian , Cooper Cyrus , Inskip Hazel , Baird Janis , Vogel Christina
Published: August 2017

Objective

To explore associations between dietary quality and access to different types of food outlets around both home and school in primary school-aged children.

Design

Cross-sectional observational study.

Setting

Hampshire, UK.

Subjects

Children (n1173) in the Southampton Women’s Survey underwent dietary assessment at age 6 years by FFQ and a standardised diet quality score was calculated. An activity space around each child’s home and school was created using ArcGIS. Cross-sectional observational food outlet data were overlaid to derive four food environment measures: counts of supermarkets, healthy specialty stores (e.g. greengrocers), fast-food outlets and total number of outlets, and a relative measure representing healthy outlets (supermarkets and specialty stores) as a proportion of total retail and fast-food outlets.

Results

In univariate multilevel linear regression analyses, better diet score was associated with exposure to greater number of healthy specialty stores (β=0·025sd/store: 95 % CI 0·007, 0·044) and greater exposure to healthy outlets relative to all outlets in children’s activity spaces (β=0·068sd/10 % increase in healthy outlets as a proportion of total outlets, 95 % CI 0·018, 0·117). After adjustment for mothers’ educational qualification and level of home neighbourhood deprivation, the relationship between diet and healthy specialty stores remained robust (P=0·002) while the relationship with the relative measure weakened (P=0·095). Greater exposure to supermarkets and fast-food outlets was associated with better diet only in the adjusted models (P=0·017 andP=0·014, respectively).

Conclusions

The results strengthen the argument for local authorities to increase the number of healthy food outlets to which young children are exposed.
Die Mannheimer Risikokinderstudie
Authors: Esser Günter , Schmidt Martin H.
Published: August 2017

Zusammenfassung. Die Mannheimer Risikokinderstudie untersucht die psychische Entwicklung und ihre Störungen bei Kindern mit unterschiedlich ausgeprägten Risiken mit dem Ziel, Empfehlungen für die Verbesserung der Prävention, Früherkennung und Frühbehandlung von psychischen Störungen bei Kindern abzuleiten. Dazu begleitet sie eine Kohorte von anfangs 384 Kindern in ihrer Entwicklung von der Geburt bis zum Erwachsenenalter. Die Erhebungen fanden in regelmäßigen Abständen statt, beginnend im Alter von 3 Monaten, mit 2 Jahren, 4;6, 8, 11, 15, 19, 22, 23 und 25 Jahren. Geplant ist eine weitere Erhebung mit ca. 30 Jahren.
Die langfristigen Auswirkungen von Frühgeburtlichkeit auf kognitive Entwicklung und Schulerfolg
Authors: Zohsel Katrin , Hohm Erika , Schmidt Martin H. , Brandeis Daniel , Banaschewski Tobias , Laucht Manfred
Published: August 2017

Zusammenfassung. In einer prospektiven Längsschnittstudie wurde der Zusammenhang zwischen früher Responsivität der Mutter und kognitiver Entwicklung ihrer früh- bzw. reifgeborenen Kinder untersucht. Im Alter von drei Monaten wurde dafür die Mutter-Kind-Interaktion mittels Verhaltensbeobachtung erfasst. Bei n=351 der teilnehmenden Kinder (101 frühgeboren) wurde die allgemeine Intelligenz (IQ) im Alter von 11 Jahren und bei n=313 (85 frühgeboren) zusätzlich der höchste erreichte Schulabschluss bis 25 Jahren erhoben. Frühgeborene wiesen mit 11 Jahren einen signifikant niedrigeren IQ als Reifgeborene auf, nachdem für mögliche konfundierende Faktoren kontrolliert worden war. Nur bei Früh-, nicht aber bei Reifgeborenen zeigte sich ein signifikanter positiver Zusammenhang zwischen mütterlicher Responsivität und IQ. Für die Wahrscheinlichkeit einen höheren Schulabschluss (mind. Fachabitur) zu erreichen, fand sich weder ein signifikanter Effekt von Frühgeburtlichkeit noch von mütterlicher Responsivität.
Individual Differences in Cognitive Reappraisal Predict Emotional	Experience Prior to Achievement Situations
Authors: Balzarotti Stefania , Chiarella Valentina , Ciceri Maria Rita
Published: August 2017

Abstract. In the present study, we examined whether individual differences in the use of cognitive reappraisal predict the experience of more positive and less negative emotions prior to an evaluative task, as well as whether reappraisal is associated with better performance. In a longitudinal design, 130 students were asked to report their spontaneous use of reappraisal as well as the emotions experienced at three time points prior to an academic exam. Results showed that the use of cognitive reappraisal measured when students began to study predicted less negative and more positive emotions in the following two weeks. Further, positive and negative affect were significant predictors of the grade achieved. Finally, cognitive reappraisal had a significant indirect effect on the grade students achieved. These findings suggest that cognitive reappraisal can be effective in regulating emotions while approaching evaluative stressors.
FGF1 protects neuroblastoma SH-SY5Y cells from p53-dependent apoptosis through an intracrine pathway regulated by FGF1 phosphorylation
Authors: Pirou Caroline , Montazer-Torbati Fatemeh , Jah Nadège , Delmas Elisabeth , Lasbleiz Christelle , Mignotte Bernard , Renaud Flore
Published: August 2017

Neuroblastoma, a sympathetic nervous system tumor, accounts for 15% of cancer deaths in children. In contrast to most human tumors, p53 is rarely mutated in human primary neuroblastoma, suggesting impaired p53 activation in neuroblastoma. Various studies have shown correlations between fgf1 expression levels and both prognosis severity and tumor chemoresistance. As we previously showed that fibroblast growth factor 1 (FGF1) inhibited p53-dependent apoptosis in neuron-like PC12 cells, we initiated the study of the interaction between the FGF1 and p53 pathways in neuroblastoma. We focused on the activity of either extracellular FGF1 by adding recombinant rFGF1 in media, or of intracellular FGF1 by overexpression in human SH-SY5Y and mouse N2a neuroblastoma cell lines. In both cell lines, the genotoxic drug etoposide induced a classical mitochondrial p53-dependent apoptosis. FGF1 was able to inhibit p53-dependent apoptosis upstream of mitochondrial events in SH-SY5Y cells by both extracellular and intracellular pathways. Both rFGF1 addition and etoposide treatment increased fgf1 expression in SH-SY5Y cells. Conversely, rFGF1 or overexpressed FGF1 had no effect on p53-dependent apoptosis and fgf1 expression in neuroblastoma N2a cells. Using different FGF1 mutants (that is, FGF1K132E, FGF1S130A and FGF1S130D), we further showed that the C-terminal domain and phosphorylation of FGF1 regulate its intracrine anti-apoptotic activity in neuroblastoma SH-SY5Y cells. This study provides the first evidence for a role of an intracrine growth factor pathway on p53-dependent apoptosis in neuroblastoma, and could lead to the identification of key regulators involved in neuroblastoma tumor progression and chemoresistance.
Topological insulators for thermoelectrics
Authors: Xu Ning , Xu Yong , Zhu Jia
Published: August 2017

Topological insulators demonstrate tremendous potential in fields of electronics and magnetism for their unique boundary states that are topologically protected against backscattering at non-magnetic impurities and defects. Intriguingly, most topological insulators are also excellent thermoelectric materials, since topological insulator and thermoelectric compounds share similar material features, such as heavy elements and narrow band gaps. While the influence of topological insulator boundary states has long been neglected in early thermoelectric research, recently this neglected issue has attracted intensive research efforts. A lot of theoretical and experimental investigations have emerged to explore the contribution of topological insulator boundary states to thermoelectricity. Here, we will review the most updated theoretical and experimental progresses, trying to offer a comprehensive understanding on the relation between thermoelectric properties and topological nature. Special emphasis will be laid on the potential of topological states for improving thermoelectric properties, to pave a new way of realizing high-performance thermoelectric devices.
α7 nicotinic acetylcholine receptor signaling modulates the inflammatory phenotype of fetal brain microglia: first evidence of interference by iron homeostasis
Authors: Cortes M. , Cao M. , Liu H. L. , Moore C. S. , Durosier L. D. , Burns P. , Fecteau G. , Desrochers A. , Barreiro L. B. , Antel J. P. , Frasch M. G.
Published: August 2017

Neuroinflammation in utero may result in life-long neurological disabilities. Microglia play a pivotal role, but the mechanisms are poorly understood. No early postnatal treatment strategies exist to enhance neuroprotective potential of microglia. We hypothesized that agonism on α7 nicotinic acetylcholine receptor (α7nAChR) in fetal microglia will augment their neuroprotective transcriptome profile, while the antagonistic stimulation of α7nAChR will achieve the opposite. Using an in vivo - in vitro model of developmental programming of neuroinflammation induced by lipopolysaccharide (LPS), we validated this hypothesis in primary fetal sheep microglia cultures re-exposed to LPS in presence of a selective α7nAChR agonist or antagonist. Our RNAseq and protein level findings show that a pro-inflammatory microglial phenotype acquired in vitro by LPS stimulation is reversed with α7nAChR agonistic stimulation. Conversely, antagonistic α7nAChR stimulation potentiates the pro-inflammatory microglial phenotype. Surprisingly, under conditions of LPS double-hit an interference of a postulated α7nAChR - ferroportin signaling pathway may impede this mechanism. These results suggest a therapeutic potential of α7nAChR agonists in early re-programming of microglia in neonates exposed to in utero inflammation via an endogenous cerebral cholinergic anti-inflammatory pathway. Future studies will assess the role of interactions between inflammation-triggered microglial iron sequestering and α7nAChR signaling in neurodevelopment.
In-line balanced detection stimulated Raman scattering microscopy
Authors: Crisafi Francesco , Kumar Vikas , Scopigno Tullio , Marangoni Marco , Cerullo Giulio , Polli Dario
Published: August 2017

We introduce a novel configuration for stimulated Raman scattering (SRS) microscopy, called In-line Balanced Detection (IBD), which employs a birefringent plate to generate a time-delayed polarization-multiplexed collinear replica of the probe, acting as a reference. Probe and reference cross the sample at the same position, thus maintaining their balance during image acquisition. IBD can be implemented in any conventional SRS setup, by adding a few simple elements, bringing its sensitivity close to the shot-noise limit even with a noisy laser. We tested IBD with a fiber-format laser system and observed signal-to-noise ratio improvement by up to 30 dB.
Intermittent muscle activity in the feedback loop of postural control system during natural quiet standing
Authors: Tanabe Hiroko , Fujii Keisuke , Kouzaki Motoki
Published: August 2017

The origin of continual body oscillation during quiet standing is a neural-muscular-skeletal closed feedback loop system that includes insufficient joint stiffness and a time delay. Thus, muscle activity and joint oscillations are nonlinear during quiet standing, making it difficult to demonstrate the muscular-skeletal relationship experimentally. Here we experimentally revealed this relationship using intermittent control theory, in which non-actuation works to stabilize the skeletal system towards equilibrium. We found that leg muscles were activated/inactivated when the state point was located in the opposite/same direction as the direction of anatomical action, which was associated with joint torque actuating the body towards equilibrium. The derivative values of stability index defined in the phase space approximately 200 ms before muscle inactivation were also larger than those before activation for some muscles. These results indicate that bipedal standing might be achieved by monitoring the rate of change of stability/instability components and generating joint torque to stabilize the body. In conclusion, muscles are likely to activate in an event-driven manner during quiet standing and a possible metric for on/off switching is SI dot, and our methodology of EMG processing could allows us to extract such event-driven intermittent muscle activities.
All-optical tunable buffering with coupled ultra-high Q whispering gallery mode microcavities
Authors: Yoshiki Wataru , Honda Yoshihiro , Tetsumoto Tomohiro , Furusawa Kentaro , Sekine Norihiko , Tanabe Takasumi
Published: August 2017

All-optical tunable buffering was recently achieved on a chip by using dynamically tuned coupled mode induced transparency, which is an optical analogue of electromagnetically induced transparency. However, the small Q s of about 105 used in those systems were limiting the maximum buffering time to a few hundred ps. Although employing an ultra-high Q whispering gallery mode (WGM) microcavity can significantly improve the maximum buffering time, the dynamic tuning of the WGM has remained challenging because thermo-optic and pressure tunings, which are widely used for WGM microcavities, have a very slow response. Here we demonstrate all-optical tunable buffering utilizing coupled ultra-high Q WGM cavities and the Kerr effect. The Kerr effect can change the refractive index instantaneously, and this allowed us to tune the WGM cavity very quickly. In addition, from among the various WGM cavities we employed a silica toroid microcavity for our experiments because it has an ultra-high Q factor (>2 × 107) and a small mode volume, and can be fabricated on a chip. Use of the Kerr effect and the silica toroid microcavity enabled us to observe an on-chip all-optical tunable buffering operation and achieve a maximum buffering time of 20 ns.
The utility of neutrophil to lymphocyte ratio and fluid sequestration as an early predictor of severe acute pancreatitis
Authors: Han Chaoqun , Zeng Jun , Lin Rong , Liu Jun , Qian Wei , Ding Zhen , Hou Xiaohua
Published: August 2017

It is important to identify the patients with high-risk progression to develop severe acute pancreatitis (SAP). The study was to assess whether neutrophil to lymphocyte ratio (NLR) and fluid sequestration (FS) could represent useful markers for predicting the severity. A total of 1639 patients who underwent clinical diagnosis of AP was performed. Various serologic and clinical parameters on admission were investigated. Chronologic change in NLR and FS were analyzed, and theirs utility for predicting severity of AP was evaluated by receiver operator characteristic (ROC) curve analysis. Correlation analysis was assessed by Spearman’s rank test. NLR and FS levels were both increased significantly in SAP and positively correlated with Ranson score and hospital stays. The ROC curve analyses showed the optimal cut-off values of NLR for admission with day0, day1, day2 were 9.64, 6.66 and 6.50, giving sensitivity of 77–82%. The optimal cut-off values of FS for admission with day1, day2, day3 were 1375 ml, 2345 ml and 3424 ml, giving sensitivity of 62–75%. Moreover, measurement of NLR and FS together exhibited a similar area under curve (AUC) and sensitivity for SAP prediction compared with the those of Ranson score. Increase of NLR and FS are correlated with severity and can be suggested as a predictive factor in an early stage of AP.
O-GlcNAcylation Reduces Ischemia-Reperfusion–Induced Brain Injury
Authors: Gu Jin-hua , Shi Jianhua , Dai Chun-ling , Ge Jian-bin , Zhao Yang , Chen Yanxing , Yu Qian , Qin Zheng-hong , Iqbal Khalid , Liu Fei , Gong Cheng-Xin
Published: August 2017

O-GlcNAcylation is a common posttranslational modification of nucleocytoplasmic proteins with β-N-acetylglucosamine (GlcNAc) and regulates numerous biological processes. By using mouse models of cerebral ischemia induced by permanent and transient middle cerebral artery occlusion (MCAO), we observed an initial elevation (~1.7-fold, 1–4 hours after ischemia) and then decline of O-GlcNAcylation during cerebral ischemia. We found that moderate increase (<3-fold) of brain O-GlcNAcylation by pharmacological means ameliorated cerebral ischemia-reperfusion injury and the consequent motor and neurological deficits. Interference of the transient elevation of O-GlcNAcylation pharmacologically or genetically aggravates the ischemia-induced brain damage, motor deficits and mortality. The alteration of O-GlcNAcylation was also seen in the ischemic areas of postmortem human brains. This study reveals an important regulation of cerebral ischemia-reperfusion injury by O-GlcNAcylation and also provides a possible therapeutic strategy, i.e., by increasing O-GlcNAcylation, to reduce the cerebral damage and improve the clinical outcome of ischemic stroke.
Combining Positive Matrix Factorization and Radiocarbon Measurements for Source Apportionment of PM2.5 from a National Background Site in North China
Authors: Wang Xiaoping , Zong Zheng , Tian Chongguo , Chen Yingjun , Luo Chunling , Li Jun , Zhang Gan , Luo Yongming
Published: August 2017

To explore the utility of combining positive matrix factorization (PMF) with radiocarbon (14C) measurements for source apportionment, we applied PM2.5 data collected for 14 months at a national background station in North China to PMF models. The solutions were compared to 14C results of four seasonally averaged samples and three outlier samples. Comparing the most readily interpretable PMF solutions and 14C results revealed that PMF modeling was well able to capture the source patterns of PM2.5 with two and three irrelevant source classifications for the seasonal and outlier samples. The contribution of sources that could not be classified as either fossil or non-fossil sources in the PMF solution, and the errors between the modeled and measured concentrations weakened the effectiveness of the comparison. Based on these two factors, we developed an index for selecting the most suitable 14C measurement samples for combining with the PMF model. Then we examined the potential for coupling PMF modeling and 14C data with a constrained PMF run using the 14C data as a priori information. The restricted run could provide a more reliable solution; however, the PMF model must provide a flexible dialog to input the priori restrictions for executing the constraint simulation.
A new mass spectrometry-based method for the quantification of histones in plasma from septic shock patients
Authors: García-Giménez J. L. , Romá-Mateo C. , Carbonell N. , Palacios L. , Peiró-Chova L. , García-López E. , García-Simón M. , Lahuerta R. , Gimenez-Garzó C. , Berenguer-Pascual E. , Mora M. I. , Valero M. L. , Alpízar A. , Corrales F. J. , Blanquer J. , Pallardó F. V.
Published: August 2017

The aim of this study was to develop a novel method to detect circulating histones H3 and H2B in plasma based on multiple reaction monitoring targeted mass spectrometry and a multiple reaction monitoring approach (MRM-MS) for its clinical application in critical bacteriaemic septic shock patients. Plasma samples from 17 septic shock patients with confirmed bacteraemia and 10 healthy controls were analysed by an MRM-MS method, which specifically detects presence of histones H3 and H2B. By an internal standard, it was possible to quantify the concentration of circulating histones in plasma, which were significantly higher in patients, and thus confirmed their potential as biomarkers for diagnosing septic shock. After comparing surviving patients and non-survivors, a correlation was found between higher levels of circulating histones and unfavourable outcome. Indeed, histone H3 proved a more efficient and sensitive biomarker for septic shock prognosis. In conclusion, these findings suggest the accuracy of the MRM-MS technique and stable isotope labelled peptides to detect and quantify circulating plasma histones H2B and H3. This method may be used for early septic shock diagnoses and for the prognosis of fatal outcomes.
Gas6 derived from cancer-associated fibroblasts promotes migration of Axl-expressing lung cancer cells during chemotherapy
Authors: Kanzaki Ryu , Naito Hisamichi , Kise Kazuyoshi , Takara Kazuhiro , Eino Daisuke , Minami Masato , Shintani Yasushi , Funaki Soichiro , Kawamura Tomohiro , Kimura Toru , Okumura Meinoshin , Takakura Nobuyuki
Published: August 2017

Alterations to the tumor stromal microenvironment induced by chemotherapy could influence the behavior of cancer cells. In the tumor stromal microenvironment, cancer-associated fibroblasts (CAFs) play an important role. Because the receptor tyrosine kinase Axl and its ligand Gas6 could be involved in promoting non-small cell lung cancer (NSCLC), we investigated the role of Gas6 secreted by CAFs during chemotherapy in NSCLC. In a murine model, we found that Gas6 expression by CAFs was upregulated following cisplatin treatment. Gas6 expression might be influenced by intratumoral hypoperfusion during chemotherapy, and it increased after serum starvation in a human lung CAF line, LCAFhTERT. Gas6 is associated with LCAFhTERT cell growth. Recombinant Gas6 promoted H1299 migration, and conditioned medium (CM) from LCAFhTERT cells activated Axl in H1299 cells and promoted migration. Silencing Gas6 in LCAFhTERT reduced the Axl activation and H1299 cell migration induced by CM from LCAFhTERT. In clinical samples, stromal Gas6 expression increased after chemotherapy. Five-year disease-free survival rates for patients with tumor Axl- and stromal Gas6-positive tumors (n = 37) was significantly worse than for the double negative group (n = 12) (21.9% vs 51.3%, p = 0.04). Based on these findings, it is presumed that Gas6 derived from CAFs promotes migration of Axl-expressing lung cancer cells during chemotherapy and is involved in poor clinical outcome.
Thiamine antagonists trigger p53-dependent apoptosis in differentiated SH-SY5Y cells
Authors: Chornyy Sergiy , Parkhomenko Yulia , Chorna Nataliya
Published: August 2017

Accumulating evidences suggest that p53 is a key coordinator of cellular events triggered by oxidative stress often associated with the impairment in thiamine metabolism and its functions. However, there are limited data regarding the pursuant feedback between p53 transactivation and thiamine homeostasis. Impairment in thiamine metabolism can be induced experimentally via interference with the thiamine uptake and/or inhibition of the thiamin pyrophosphate–dependent enzymes using thiamine antagonists - amprolium (AM), oxythiamine (OT) or pyrithiamine (PT). We found that exposure of neuronally differentiated SH-SY5Y cells to AM, OT and PT triggered upregulation of p53 gene expression, post-translational modification of p53 via phosphorylation and activation of p53 DNA-binding activity. Phosphorylation of p53 at Ser20 was equally efficient in upregulation of thiamine transporter 1 (THTR1) by all antagonists. However, induction of the expressions of the pyruvate dehydrogenase E1 component subunit beta (PDHB) and oxoglutarate dehydrogenase (OGDH) required dual phosphorylation of p53 at Ser9 and Ser20, seen in cells treated with PT and OT. Moreover, pretreatment of the cells with a decoy oligonucleotide carrying wild-type p53-response element markedly attenuated OT-induced THTR1, PDHB and OGDH gene expression suggesting an important role of p53 in transactivation of these genes. Finally, analysis of gene and metabolic networks showed that OT triggers cell apoptosis through the p53-dependent intrinsic pathway.
Accelerated Healing of Diabetic Wounds Treated with L-Glutamic acid Loaded Hydrogels Through Enhanced Collagen Deposition and Angiogenesis: An In Vivo Study
Authors: Thangavel Ponrasu , Ramachandran Balaji , Chakraborty Sudip , Kannan Ramya , Lonchin Suguna , Muthuvijayan Vignesh
Published: August 2017

We have developed L-glutamic acid (LG) loaded chitosan (CS) hydrogels to treat diabetic wounds. Although literature reports wound healing effects of poly(glutamic acid)-based materials, there are no studies on the potential of L-glutamic acid in treating diabetic wounds. As LG is a direct precursor for proline synthesis, which is crucial for collagen synthesis, we have prepared CS + LG hydrogels to accelerate diabetic wound healing. Physiochemical properties of the CS + LG hydrogels showed good swelling, thermal stability, smooth surface morphology, and controlled biodegradation. The addition of LG to CS hydrogels did not alter their biocompatibility significantly. CS + LG hydrogel treatment showed rapid wound contraction compared to control and chitosan hydrogel. Period of epithelialization is significantly reduced in CS + LG hydrogel treated wounds (16 days) compared to CS hydrogel (20 days), and control (26 days). Collagen synthesis and crosslinking are also significantly improved in CS + LG hydrogel treated diabetic rats. Histopathology and immunohistochemistry results revealed that the CS + LG hydrogel dressing accelerated vascularization and macrophage recruitment to enhance diabetic wound healing. These results demonstrate that incorporation of LG can improve collagen deposition, and vascularization, and aid in faster tissue regeneration. Therefore, CS + LG hydrogels could be an effective wound dressing used to treat diabetic wounds.
Hyper-O-GlcNAcylation induces cisplatin resistance via regulation of p53 and c-Myc in human lung carcinoma
Authors: Luanpitpong Sudjit , Angsutararux Paweorn , Samart Parinya , Chanthra Nawin , Chanvorachote Pithi , Issaragrisil Surapol
Published: August 2017

Aberrant metabolism in hexosamine biosynthetic pathway (HBP) has been observed in several cancers, affecting cellular signaling and tumor progression. However, the role of O-GlcNAcylation, a post-translational modification through HBP flux, in apoptosis remains unclear. Here, we found that hyper-O-GlcNAcylation in lung carcinoma cells by O-GlcNAcase inhibition renders the cells to apoptosis resistance to cisplatin (CDDP). Profiling of various key regulatory proteins revealed an implication of either p53 or c-Myc in the apoptosis regulation by O-GlcNAcylation, independent of p53 status. Using co-immunoprecipitation and correlation analyses, we found that O-GlcNAcylation of p53 under certain cellular contexts, i.e. high p53 activation, promotes its ubiquitin-mediated proteasomal degradation, resulting in a gain of oncogenic and anti-apoptotic functions. By contrast, O-GlcNAcylation of c-Myc inhibits its ubiquitination and subsequent proteasomal degradation. Gene manipulation studies revealed that O-GlcNAcylation of p53/c-Myc is in part a regulator of CDDP-induced apoptosis. Accordingly, we classified CDDP resistance by hyper-O-GlcNAcylation in lung carcinoma cells as either p53 or c-Myc dependence based on their molecular targets. Together, our findings provide novel mechanisms for the regulation of lung cancer cell apoptosis that could be important in understanding clinical drug resistance and suggest O-GlcNAcylation as a potential target for cancer therapy.
Recovery of woody plant species richness in secondary forests in China: a meta-analysis
Authors: Liu Xiaofei , Liu Xuehua , Skidmore Andrew , Garcia Claude
Published: August 2017

There is considerable uncertainty concerning changes in plant diversity of Chinese secondary forests, particularly with respect to diversity recovery following anthropogenic disturbance. Here we present a meta-analysis of the recovery of woody plant species richness in secondary forests in China, with nearby primary forests as a reference. A total of 125 pairs of secondary-primary forest data reported in 55 publications were identified across China. We analyzed the data by region and logging history to examine their influences on secondary forest recovery. Our results indicated that the woody plant richness of secondary forests in China was close to fully recovered when compared to the primary forest, with the recovery ratio being 85–103%. Higher recovery ratios were observed in central, northeast and southwest China, with lower recovery ratios seen in east, south and northwest China, and the recovery in central China significantly reached the primary forests (reference) level. Concerning logging histories, the recovery ratios showed two peak values, with one at 21–40 years after clear cutting and the other at 61–80 years. We reveal the fundamental recovery patterns of woody plant species richness in secondary forests in China. These patterns provide information for the sustainable management of secondary forest resources.
Persistence within dendritic cells marks an antifungal evasion and dissemination strategy of Aspergillus terreus
Authors: Hsieh Shih-Hung , Kurzai Oliver , Brock Matthias
Published: August 2017

Aspergillus terreus is an airborne human fungal pathogen causing life-threatening invasive aspergillosis in immunocompromised patients. In contrast to Aspergillus fumigatus, A. terreus infections are associated with high dissemination rates and poor response to antifungal treatment. Here, we compared the interaction of conidia from both fungal species with MUTZ-3-derived dendritic cells (DCs). After phagocytosis, A. fumigatus conidia rapidly escaped from DCs, whereas A. terreus conidia remained persisting with long-term survival. Escape from DCs was independent from DHN-melanin, as A. terreus conidia expressing wA showed no increased intracellular germination. Within DCs A. terreus conidia were protected from antifungals, whereas A. fumigatus conidia were efficiently cleared. Furthermore, while A. fumigatus conidia triggered expression of DC activation markers such as CD80, CD83, CD54, MHCII and CCR7, persistent A. terreus conidia were significantly less immunogenic. Moreover, DCs confronted with A. terreus conidia neither produced pro-inflammatory nor T-cell stimulating cytokines. However, TNF-α addition resulted in activation of DCs and provoked the expression of migration markers without inactivating intracellular A. terreus conidia. Therefore, persistence within DCs and possibly within other immune cells might contribute to the low response of A. terreus infections to antifungal treatment and could be responsible for its high dissemination rates.
Sponge bioerosion on changing reefs: ocean warming poses physiological constraints to the success of a photosymbiotic excavating sponge
Authors: Achlatis Michelle , van der Zande Rene M. , Schönberg Christine H. L. , Fang James K. H. , Hoegh-Guldberg Ove , Dove Sophie
Published: August 2017

Excavating sponges are prominent bioeroders on coral reefs that in comparison to other benthic organisms may suffer less or may even benefit from warmer, more acidic and more eutrophic waters. Here, the photosymbiotic excavating sponge Cliona orientalis from the Great Barrier Reef was subjected to a prolonged simulation of both global and local environmental change: future seawater temperature, partial pressure of carbon dioxide (as for 2100 summer conditions under “business-as-usual” emissions), and diet supplementation with particulate organics. The individual and combined effects of the three factors on the bioerosion rates, metabolic oxygen and carbon flux, biomass change and survival of the sponge were monitored over the height of summer. Diet supplementation accelerated bioerosion rates. Acidification alone did not have a strong effect on total bioerosion or survival rates, yet it co-occurred with reduced heterotrophy. Warming above 30 °C (+2.7 °C above the local maximum monthly mean) caused extensive bleaching, lower bioerosion, and prevailing mortality, overriding the other factors and suggesting a strong metabolic dependence of the sponge on its resident symbionts. The growth, bioerosion capacity and likelihood of survival of C. orientalis and similar photosymbiotic excavating sponges could be substantially reduced rather than increased on end-of-the-century reefs under “business-as-usual” emission profiles.
Supercurrent switch in π topological junctions based upon a narrow quantum spin Hall insulator
Authors: Yu Qingyun , Tao Ze , Song Juntao , Tao Y. C. , Wang Jun
Published: August 2017

The narrow quantum spin Hall (QSH) insulator is characterized by interedge coupling, which could feature exotic transport phenomena, and thus serves as the key element for topological superconducting electronic devices. Herein, we theoretically explore possible Josephson π states in a QSH insulator strip touching on two s-wave superconductors in the presence of the interedge coupling. It is shown that the interedge coupling could give rise to a 0 − π transition modulated by the gate voltage, originating from an additional π phase difference caused by the interedge backscattering. The 0 − π transition in turn can manifest the helical spin texture of the edge states. A considerable residual value of the supercurrent at the 0 − π transition point is always exhibited, suggesting a very efficient performance of the device as a supercurrent switch. Moreover, the region of coexisting 0 and π states is found fairly large, which can be used to improve accuracy in the design of a π superconducting quantum interference device.
Selection of reference genes suitable for normalization of qPCR data under abiotic stresses in bioenergy crop Arundo donax L.
Authors: Poli Michele , Salvi Silvio , Li Mingai , Varotto Claudio
Published: August 2017

Suitable reference gene selection in qRT-PCR is a key pre-requisite to produce reliable data in gene expression analyses. In this study, novel primers for six commonly used reference genes (AC1, TLF, Act2, TUB α, EF-1α and GAPDH) plus two new candidates (pDUF221 and RPN6) were designed and comparatively tested for expression stability under abiotic stresses (osmotic, heavy metal and heat shock) in shoot, root and their combination of Arundo donax L., a raising non-food energy crop. Expression stability rankings from the most to the least stable gene in each condition and in two tissues (young shoots and roots) were generated with geNorm, NormFinder and BestKeeper programs. All programs provided similar rankings and, strikingly, in most cases identified one of the new candidates, RPN6, as the most suitable reference gene. This novel set of reliable references allows to choose either the best combination of reference genes across multiple stress/organ conditions or to select condition-specific genes that can improve the quality of qRT-PCR analysis. This work provides a solid basis for the functional characterization of A. donax, by enabling accurate quantification of the transcriptional responsiveness under a series of common stress conditions of any gene of interest in this promising biomass/bioenergy species.
Dietary iron restriction alleviates renal tubulointerstitial injury induced by protein overload in mice
Authors: Ikeda Yasumasa , Horinouchi Yuya , Hamano Hirofumi , Hirayama Tasuku , Kishi Seiji , Izawa-Ishizawa Yuki , Imanishi Masaki , Zamami Yoshito , Takechi Kenshi , Miyamoto Licht , Ishizawa Keisuke , Aihara Ken-ichi , Nagasawa Hideko , Tsuchiya Koichiro , Tamaki Toshiaki
Published: August 2017

Increased proteinuria causes tubulointerstitial injury due to inflammation in chronic kidney disease (CKD). Iron restriction exhibits protective effects against renal dysfunction; however, its effects against protein overload-induced tubulointerstitial damage remain unclear. Here, we investigated dietary iron restriction effect on tubulointerstitial damage in mice with protein-overload tubulointerstitial injury. Renal tubulointerstitial injury in animal model was induced by intraperitoneal injection of an overdose of bovine serum albumin (BSA). We divided mice into three groups: normal saline + normal diet (ND), BSA + ND, and BSA + iron-restricted diet (IRD). BSA overload induced renal tubulointerstitial injury in the ND mice, which was ameliorated in the IRD mice. Inflammatory cytokines and extracellular matrix mRNA expression was upregulated in BSA + ND mice kidneys and was inhibited by IRD. BSA-induced increase in renal superoxide production, NADPH oxidase activity, and p22phox expression was diminished in the IRD mice. IRD suppression increased BSA-induced renal macrophage infiltration. Moreover, BSA mice exhibited nucleotide-binding oligomerisation domain-like receptor pyrin domain-containing protein (NLRP) inflammasome activation, which was inhibited by IRD. Ferrous iron increased in kidneys with BSA overload and was inhibited by IRD. Thus, iron restriction inhibited oxidative stress and inflammatory changes, contributing to the protective effect against BSA overload-induced tubulointerstitial injury.
Identification of oriT and a recombination hot spot in the IncA/C plasmid backbone
Authors: Hegyi Anna , Szabó Mónika , Olasz Ferenc , Kiss János
Published: August 2017

Dissemination of multiresistance has been accelerating among pathogenic bacteria in recent decades. The broad host-range conjugative plasmids of the IncA/C family are effective vehicles of resistance determinants in Gram-negative bacteria. Although more than 150 family members have been sequenced to date, their conjugation system and other functions encoded by the conserved plasmid backbone have been poorly characterized. The key cis-acting locus, the origin of transfer (oriT), has not yet been unambiguously identified. We present evidence that IncA/C plasmids have a single oriT locus immediately upstream of the mobI gene encoding an indispensable transfer factor. The fully active oriT spans ca. 150-bp AT-rich region overlapping the promoters of mobI and contains multiple inverted and direct repeats. Within this region, the core domain of oriT with reduced but detectable transfer activity was confined to a 70-bp segment containing two inverted repeats and one copy of a 14-bp direct repeat. In addition to oriT, a second locus consisting of a 14-bp imperfect inverted repeat was also identified, which mimicked the function of oriT but which was found to be a recombination site. Recombination between two identical copies of these sites is RecA-independent, requires a plasmid-encoded recombinase and resembles the functioning of dimer-resolution systems.
RhoA-ROCK Inhibition Reverses Synaptic Remodeling and Motor and Cognitive Deficits Caused by Traumatic Brain Injury
Authors: Mulherkar Shalaka , Firozi Karen , Huang Wei , Uddin Mohammad Danish , Grill Raymond J. , Costa-Mattioli Mauro , Robertson Claudia , Tolias Kimberley F.
Published: August 2017

Traumatic brain injury (TBI) causes extensive neural damage, often resulting in long-term cognitive impairments. Unfortunately, effective treatments for TBI remain elusive. The RhoA-ROCK signaling pathway is a potential therapeutic target since it is activated by TBI and can promote the retraction of dendritic spines/synapses, which are critical for information processing and memory storage. To test this hypothesis, RhoA-ROCK signaling was blocked by RhoA deletion from postnatal neurons or treatment with the ROCK inhibitor fasudil. We found that TBI impairs both motor and cognitive performance and inhibiting RhoA-ROCK signaling alleviates these deficits. Moreover, RhoA-ROCK inhibition prevents TBI-induced spine remodeling and mature spine loss. These data argue that TBI elicits pathological spine remodeling that contributes to behavioral deficits by altering synaptic connections, and RhoA-ROCK inhibition enhances functional recovery by blocking this detrimental effect. As fasudil has been safely used in humans, our results suggest that it could be repurposed to treat TBI.
Enhanced tensile strength and thermal conductivity in copper diamond composites with B4C coating
Authors: Sun Youhong , He Linkai , Zhang Chi , Meng Qingnan , Liu Baochang , Gao Ke , Wen Mao , Zheng Weitao
Published: August 2017

Boron carbide (B4C) coating on diamond particle is synthesized by heating diamond particles in a powder mix of H3BO3 and B in Ar atmosphere. The composition, bond state and coverage fraction of boron carbide coating on diamond particles are investigated. The boron carbide coating favors to grow on diamond (100) surface rather than on diamond (111) surface. Cu matrix composites reinforced with B4C-coated diamond particles were made by powder metallurgy. The addition of B4C coating gave rise to a dense composite. The influence of B4C coating on both tensile strength and thermal conductivity of the composite were investigated. When the B4C fully covered on diamond particles, the composite exhibited a greatly increase in tensile strength (115 MPa) which was much higher than that for uncoated-diamond/Cu (60 MPa) composites. Meanwhile, a high thermal conductivity of 687 W/mK was achieved in the B4C-coated-diamond/Cu composites.
A Universal Isotherm Model to Capture Adsorption Uptake and Energy Distribution of Porous Heterogeneous Surface
Authors: Ng Kim Choon , Burhan Muhammad , Shahzad Muhammad Wakil , Ismail Azahar Bin
Published: August 2017

The adsorbate-adsorbent thermodynamics are complex as it is influenced by the pore size distributions, surface heterogeneity and site energy distribution, as well as the adsorbate properties. Together, these parameters defined the adsorbate uptake forming the state diagrams, known as the adsorption isotherms, when the sorption site energy on the pore surfaces are favorable. The available adsorption models for describing the vapor uptake or isotherms, hitherto, are individually defined to correlate to a certain type of isotherm patterns. There is yet a universal approach in developing these isotherm models. In this paper, we demonstrate that the characteristics of all sorption isotherm types can be succinctly unified by a revised Langmuir model when merged with the concepts of Homotattic Patch Approximation (HPA) and the availability of multiple sets of site energy accompanied by their respective fractional probability factors. The total uptake (q/q*) at assorted pressure ratios (P/P
s
) are inextricably traced to the manner the site energies are spread, either naturally or engineered by scientists, over and across the heterogeneous surfaces. An insight to the porous heterogeneous surface characteristics, in terms of adsorption site availability has been presented, describing the unique behavior of each isotherm type.