bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cryo-EM and the elucidation of new macromolecular structures: Random Conical Tilt revisited
Authors: Sorzano C. O. S. , Alcorlo M. , de la Rosa-Trevín J. M. , Melero R. , Foche I. , Zaldívar-Peraza A. , del Cano L. , Vargas J. , Abrishami V. , Otón J. , Marabini R. , Carazo J. M. 
Published: September 2015

AbstractCryo-Electron Microscopy (cryo-EM) of macromolecular complexes is a fundamental structural biology technique which is expanding at a very fast pace. Key to its success in elucidating the three-dimensional structure of a macromolecular complex, especially of small and non-symmetric ones, is the ability to start from a low resolution map, which is subsequently refined with the actual images collected at the microscope. There are several methods to produce this first structure. Among them, Random Conical Tilt (RCT) plays a prominent role due to its unbiased nature (it can create an initial model based on experimental measurements). In this article, we revise the fundamental mathematical expressions supporting RCT, providing new expressions handling all key geometrical parameters without the need of intermediate operations, leading to improved automation and overall reliability, essential for the success of cryo-EM when analyzing new complexes. We show that the here proposed RCT workflow based on the new formulation performs very well in practical cases, requiring very few image pairs (as low as 13 image pairs in one of our examples) to obtain relevant 3D maps.
Tumour-promoting role of SOCS1 in colorectal cancer cells
Authors: Tobelaim William S. , Beaurivage Claudia , Champagne Audrey , Pomerleau Véronique , Simoneau Aline , Chababi Walid , Yeganeh Mehdi , Thibault Philippe , Klinck Roscoe , Carrier Julie C. , Ferbeyre Gerardo , Ilangumaran Subburaj , Saucier Caroline 
Published: September 2015

AbstractThe SOCS1 (Suppressor Of Cytokine Signalling 1) protein is considered a tumour suppressor. Notably, the SOCS1 gene is frequently silenced in cancer by hypermethylation of its promoter. Besides blocking inflammation, SOCS1 tumour suppressor activity involves Met receptor inhibition and enhancement of p53 tumour suppressor activity. However, the role of SOCS1 in colorectal cancer (CRC) remains understudied and controversial. Here, we investigated SOCS1 relevance for CRC by querying gene expression datasets of human CRC specimens from The Cancer Genome Atlas (TCGA) and by SOCS1 gain/loss-of-function analyses in murine and human colon carcinoma cells. Our results show that SOCS1 mRNA levels in tumours were more often elevated than reduced with respect to matched adjacent normal tissue of CRC specimens (n = 41). The analysis of TCGA dataset of 431 CRC patients revealed no correlation between SOCS1 expression and overall survival. Overexpression of SOCS1 in CRC cells triggered cell growth enhancement, anchorage-independent growth and resistance to death stimuli, whereas knockdown of SOCS1 reduced these oncogenic features. Moreover, SOCS1 overexpression in mouse CT26 cells increased tumourigenesis in vivo. Biochemical analyses showed that SOCS1 pro-oncogenic activity correlated with the down-modulation of STAT1 expression. Collectively, these results suggest that SOCS1 may work as an oncogene in CRC.
Effect of anthropogenic sulphate aerosol in China on the drought in the western-to-central US
Authors: Yeh Sang-Wook , Park Rokjin J. , Kim Minjoong J. , Jeong Jaein I. , Song Chang-Keun 
Published: September 2015

AbstractIn recent decades, droughts have occurred in the western-to-central United States (US), significantly affecting food production, water supplies, ecosystem health and the propagation of vector-borne diseases. Previous studies have suggested natural sea surface temperature (SST) forcing in the Pacific as the main driver of precipitation deficits in the US. Here, we show that the aerosol forcing in China, which has been known to alter the regional hydrological cycle in East Asia, may also contribute to reducing the precipitation in the western-to-central US through atmospheric teleconnections across the Pacific. Our model experiments show some indications that both the SST forcing and the increase in regional sulphate forcing in China play a similar role in modulating the western-to-central US precipitation, especially its long-term variation. This result indicates that regional air quality regulations in China have important implications for hydrological cycles in East Asia, as well as in the US.
Efficient single photon source based on μ-fibre-coupled tunable microcavity
Authors: Lee Chang-Min , Lim Hee-Jin , Schneider Christian , Maier Sebastian , Höfling Sven , Kamp Martin , Lee Yong-Hee 
Published: September 2015

AbstractEfficient and fast on-demand single photon sources have been sought after as critical components of quantum information science. We report an efficient and tunable single photon source based on an InAs quantum dot (QD) embedded in a photonic crystal cavity coupled with a highly curved μ-fibre. Exploiting evanescent coupling between the μ-fibre and the cavity, a high collection efficiency of 23% and Purcell-enhanced spontaneous emissions are observed. In our scheme, the spectral position of a resonance can be tuned by as much as 1.5 nm by adjusting the contact position of the μ-fibre, which increases the spectral coupling probability between the QD and the cavity mode. Taking advantage of the high photon count rate and the tunability, the collection efficiencies and the decay rates are systematically investigated as a function of the QD–cavity detuning.
Genome-wide homozygosity signature and risk of Hodgkin lymphoma
Authors: Sud Amit , Cooke Rosie , Swerdlow Anthony J. , Houlston Richard S. 
Published: September 2015

AbstractRecent studies have reported that regions of homozygosity (ROH) in the genome are detectable in outbred populations and can be associated with an increased risk of malignancy. To examine whether homozygosity is associated with an increased risk of developing Hodgkin lymphoma (HL) we analysed 589 HL cases and 5,199 controls genotyped for 484,072 tag single nucleotide polymorphisms (SNPs). Across the genome the cumulative distribution of ROH was not significantly different between cases and controls. Seven ROH at 4q22.3, 4q32.2, 7p12.3–14.1, 7p22.2, 10p11.22–23, 19q13.12-2 and 19p13.2 were associated with HL risk at P < 0.01. Intriguingly 4q22.3 harbours an ROH to which the nuclear factor NF-kappa-B p105 subunit (NFKB1) maps (P = 0.002). The ROH at 19q13.12-2 has previously been implicated in B-cell precursor acute lymphoblastic leukaemia. Aside from these observations which require validation, it is unlikely that levels of measured homozygosity caused by autozygosity, uniparental isodisomy or hemizygosity play a major role in defining HL risk in predominantly outbred populations.
Information complementarity: A new paradigm for decoding quantum incompatibility
Authors: Zhu Huangjun 
Published: September 2015

AbstractThe existence of observables that are incompatible or not jointly measurable is a characteristic feature of quantum mechanics, which lies at the root of a number of nonclassical phenomena, such as uncertainty relations, wave—particle dual behavior, Bell-inequality violation and contextuality. However, no intuitive criterion is available for determining the compatibility of even two (generalized) observables, despite the overarching importance of this problem and intensive efforts of many researchers. Here we introduce an information theoretic paradigm together with an intuitive geometric picture for decoding incompatible observables, starting from two simple ideas: Every observable can only provide limited information and information is monotonic under data processing. By virtue of quantum estimation theory, we introduce a family of universal criteria for detecting incompatible observables and a natural measure of incompatibility, which are applicable to arbitrary number of arbitrary observables. Based on this framework, we derive a family of universal measurement uncertainty relations, provide a simple information theoretic explanation of quantitative wave—particle duality and offer new perspectives for understanding Bell nonlocality, contextuality and quantum precision limit.
Metformin Increases Sensitivity of Pancreatic Cancer Cells to Gemcitabine by Reducing CD133+ Cell Populations and Suppressing ERK/P70S6K Signaling
Authors: Chai Xinqun , Chu Hongpeng , Yang Xuan , Meng Yuanpu , Shi Pengfei , Gou Shanmiao 
Published: September 2015

AbstractThe prognosis of pancreatic cancer remains dismal, with little advance in chemotherapy because of its high frequency of chemoresistance. Metformin is widely used to treat type II diabetes and was shown recently to inhibit pancreatic cancer stem cell proliferation. In the present study, we investigated the role of metformin in chemoresistance of pancreatic cancer cells to gemcitabine and its possible cellular and molecular mechanisms. Metformin increases sensitivity of pancreatic cancer cells to gemcitabine. The mechanism involves, at least in part, the inhibition of CD133+ cells proliferation and suppression of P70S6K signaling activation via inhibition of ERK phosphorylation. Studies of primary tumor samples revealed a relationship between P70S6K signaling activation and the malignancy of pancreatic cancer. Analysis of clinical data revealed a trend of the benefit of metformin for pancreatic cancer patients with diabetes. The results suggested that metformin has a potential clinical use in overcoming chemoresistance of pancreatic cancer.
Dietary supplementation with n-3 fatty acids from weaning limits brain biochemistry and behavioural changes elicited by prenatal exposure to maternal inflammation in the mouse model
Authors: Li Q , Leung Y O , Zhou I , Ho L C , Kong W , Basil P , Wei R , Lam S , Zhang X , Law A C K , Chua S E , Sham P C , Wu E X , McAlonan G M 
Published: September 2015

AbstractPrenatal exposure to maternal immune activation (MIA) increases the risk of schizophrenia and autism in the offspring. The MIA rodent model provides a valuable tool to directly test the postnatal consequences of exposure to an early inflammatory insult; and examine novel preventative strategies. Here we tested the hypotheses that behavioural differences in the MIA mouse model are accompanied by in vivo and ex vivo alterations in brain biochemistry; and that these can be prevented by a post-weaning diet enriched with n-3 polyunsaturated fatty acid (PUFA). The viral analogue PolyI:C (POL) or saline (SAL) was administered to pregnant mice on gestation day 9. Half the resulting male offspring (POL=21; SAL=17) were weaned onto a conventional lab diet (n-6 PUFA); half were weaned onto n-3 PUFA-enriched diet. In vivo magnetic resonance spectroscopy measures were acquired prior to behavioural tests; glutamic acid decarboxylase 67 (GAD67) and tyrosine hydroxylase protein levels were measured ex vivo. The main findings were: (i) Adult MIA-exposed mice fed a standard diet had greater N-acetylaspartate/creatine (Cr) and lower myo-inositol/Cr levels in the cingulate cortex in vivo. (ii) The extent of these metabolite differences was correlated with impairment in prepulse inhibition. (iii) MIA-exposed mice on the control diet also had higher levels of anxiety and altered levels of GAD67ex vivo. (iv) An n-3 PUFA diet prevented all the in vivo and ex vivo effects of MIA observed. Thus, n-3 PUFA dietary enrichment from early life may offer a relatively safe and non-toxic approach to limit the otherwise persistent behavioural and biochemical consequences of prenatal exposure to inflammation. This result may have translational importance.
Impact of 5-HTTLPR on hippocampal subregional activation in older adults
Authors: Garrett A , Gupta S , Reiss A L , Waring J , Sudheimer K , Anker L , Sosa N , Hallmayer J F , O’Hara R 
Published: September 2015

AbstractStudies have shown that a functional polymorphism of the serotonin transporter gene (5-HTTLPR) impacts performance on memory-related tasks and the hippocampal structures that subserve these tasks. The short (s) allele of 5-HTTLPR has been linked to greater susceptibility for impaired memory and smaller hippocampal volume compared to the long allele (l). However, previous studies have not examined the associations between 5-HTTLPR allele and activation in subregions of the hippocampus. In this study, we used functional magnetic resonance imaging (fMRI) to measure activation in hippocampal and temporal lobe subregions in 36 elderly non-clinical participants performing a face–name encoding and recognition task. Although there were no significant differences in task performance between s allele carriers and l homozygotes, right CA1 and right parahippocampal activation during recognition errors was significantly greater in individuals bearing the s allele. In an exploratory analysis, we determined that these effects were more pronounced in s allele carriers with the apolipoprotein ɛ4 allele. Our results suggest that older individuals with the s allele inefficiently allocate neural resources while making errors in recognizing face–name associations, which could negatively impact memory performance during more challenging tasks.
Predictors of placebo response in pharmacological and dietary supplement treatment trials in pediatric autism spectrum disorder: a meta-analysis
Authors: Masi A , Lampit A , Glozier N , Hickie I B , Guastella A J 
Published: September 2015

AbstractLarge placebo responses in many clinical trials limit our capacity to identify effective therapeutics. Although it is often assumed that core behaviors in children with autism spectrum disorders (ASDs) rarely remit spontaneously, there has been limited investigation of the size of the placebo response in relevant clinical trials. These trials also rely on caregiver and clinical observer reports as outcome measures. The objectives of this meta-analysis are to identify the pooled placebo response and the predictors of placebo response in pharmacological and dietary supplement treatment trials for participants with a diagnosis of ASD. Randomized controlled trials (RCTs) in pediatric ASD, conducted between 1980 and August 2014, were identified through a search of Medline, EMBASE, Web of Science, Cochrane Database of Systematic Reviews and clinicaltrials.gov. RCTs of at least 14 days duration, comparing the treatment response for an oral active agent and placebo using at least one of the common outcome measures, were included. Analysis of 25 data sets (1315 participants) revealed a moderate effect size for overall placebo response (Hedges’ g=0.45, 95% confidence interval (0.34–0.56), P<0.001). Five factors were associated with an increase in response to placebo, namely: an increased response to the active intervention; outcome ratings by clinicians (as compared with caregivers); trials of pharmacological and adjunctive interventions; and trials located in Iran. There is a clear need for the identification of objective measures of change in clinical trials for ASD, such as evaluation of biological activity or markers, and for consideration of how best to deal with placebo response effects in trial design and analyses.
Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus
Authors: Kroeze Y , Peeters D , Boulle F , van den Hove D L A , van Bokhoven H , Zhou H , Homberg J R 
Published: September 2015

AbstractThe selective serotonin reuptake inhibitor (SSRI) fluoxetine is widely prescribed for the treatment of symptoms related to a variety of psychiatric disorders. After chronic SSRI treatment, some symptoms remediate on the long term, but the underlying mechanisms are not yet well understood. Here we studied the long-term consequences (40 days after treatment) of chronic fluoxetine exposure on genome-wide gene expression. During the treatment period, we measured body weight; and 1 week after treatment, cessation behavior in an SSRI-sensitive anxiety test was assessed. Gene expression was assessed in hippocampal tissue of adult rats using transcriptome analysis and several differentially expressed genes were validated in independent samples. Gene ontology analysis showed that upregulated genes induced by chronic fluoxetine exposure were significantly enriched for genes involved in myelination. We also investigated the expression of myelination-related genes in adult rats exposed to fluoxetine at early life and found two myelination-related genes (Transferrin (Tf) and Ciliary neurotrophic factor (Cntf)) that were downregulated by chronic fluoxetine exposure. Cntf, a neurotrophic factor involved in myelination, showed regulation in opposite direction in the adult versus neonatally fluoxetine-exposed groups. Expression of myelination-related genes correlated negatively with anxiety-like behavior in both adult and neonatally fluoxetine-exposed rats. In conclusion, our data reveal that chronic fluoxetine exposure causes on the long-term changes in expression of genes involved in myelination, a process that shapes brain connectivity and contributes to symptoms of psychiatric disorders.
Early-life serotonin dysregulation affects the migration and positioning of cortical interneuron subtypes
Authors: Frazer S , Otomo K , Dayer A 
Published: September 2015

AbstractEarly-life deficiency of the serotonin transporter (SERT) gives rise to a wide range of psychiatric-relevant phenotypes; however, the molecular and cellular targets of serotonin dyregulation during neural circuit formation remain to be identified. Interestingly, migrating cortical interneurons (INs) derived from the caudal ganglionic eminence (CGE) have been shown to be more responsive to serotonin-mediated signalling compared with INs derived from the medial ganglionic eminence (MGE). Here we investigated the impact of early-life SERT deficiency on the migration and positioning of CGE-derived cortical INs in SERT-ko mice and in mice exposed to the SERT inhibitor fluoxetine during the late embryonic period. Using confocal time-lapse imaging and microarray-based expression analysis we found that genetic and pharmacological SERT deficiency significantly increased the migratory speed of CGE-derived INs and affected transcriptional programmes regulating neuronal migration. Postnatal studies revealed that SERT deficiency altered the cortical laminar distribution of subtypes of CGE-derived INs but not MGE-derived INs. More specifically, we found that the distribution of vasointestinal peptide (VIP)-expressing INs in layer 2/3 was abnormal in both genetic and pharmacological SERT-deficiency models. Collectively, these data indicate that early-life SERT deficiency has an impact on the migration and molecular programmes of CGE-derived INs, thus leading to specific alterations in the positioning of VIP-expressing INs. These data add to the growing evidence that early-life serotonin dysregulation affects cortical microcircuit formation and contributes to the emergence of psychiatric-relevant phenotypes.
Predicting the birth of a spoken word
Authors: Roy Brandon C. , Frank Michael C. , DeCamp Philip , Miller Matthew , Roy Deb 
Published: September 2015

Significance
The emergence of productive language is a critical milestone in a child’s life. Laboratory studies have identified many individual factors that contribute to word learning, and larger scale studies show correlations between aspects of the home environment and language outcomes. To date, no study has compared across many factors involved in word learning. We introduce a new ultradense set of recordings that capture a single child’s daily experience during the emergence of language. We show that words used in distinctive spatial, temporal, and linguistic contexts are produced earlier, suggesting they are easier to learn. These findings support the importance of multimodal context in word learning for one child and provide new methods for quantifying the quality of children’s language input.
Cognate interaction with iNKT cells expands IL-10–producing B regulatory cells
Authors: Vomhof-DeKrey Emilie E. , Yates Jennifer , Hägglöf Thomas , Lanthier Paula , Amiel Eyal , Veerapen Natacha , Besra Gurdyal S. , Karlsson Mikael C. I. , Leadbetter Elizabeth A. 
Published: September 2015

SignificanceInvariant natural killer T (iNKT) cells can facilitate B-cell responses by enhancing helper signals from protein-specific T cells or independently induce a B-cell developmental program; however, key differences in humoral memory after iNKT-cell help remain unclear. We determined that, unlike protein-specific T-cell help, cognate iNKT-cell help expands a large number of IL-10–producing B10 regulatory cells. These findings have broad implications for the types of B cells that may be generated when synthetic iNKT glycolipid ligands are used as vaccine adjuvants and also, outline a direct means to elicit B regulatory cells, which are increasingly being pursued as immunotherapeutic targets for protection against autoimmune disease.
Direct measurement of the 3-dimensional DNA lesion distribution induced by energetic charged particles in a mouse model tissue
Authors: Mirsch Johanna , Tommasino Francesco , Frohns Antonia , Conrad Sandro , Durante Marco , Scholz Michael , Friedrich Thomas , Löbrich Markus 
Published: September 2015

Significance
Charged particles are applied in cancer radiotherapy because they are more efficient than X-rays or γ-rays in tumor cell killing. This efficiency results from the high dose deposition along the path of the particles. However, charged particles damage tissue inhomogeneously, such that many cells not directly hit by the particles receive a low dose and can survive with mutations. Because mutations can lead to secondary malignancies, this effect limits the applicability of charged particles in cancer radiotherapy. We provide the first direct measurement of the 3D DNA lesion distribution induced by energetic charged particles in a mouse model tissue. Our detailed analysis of the dose distribution will serve to benchmark biophysical models currently used for irradiation planning in cancer radiotherapy.
Type II integral membrane protein, TM of J paramyxovirus promotes cell-to-cell fusion
Authors: Li Zhuo , Hung Cher , Paterson Reay G. , Michel Frank , Fuentes Sandra , Place Ryan , Lin Yuan , Hogan Robert J. , Lamb Robert A. , He Biao 
Published: September 2015

Significance
J paramyxovirus represents a group of unclassified paramyxoviruses that encode an integral membrane protein, transmembrane (TM), that is not found in other classified paramyxoviruses. In this work we have found that TM expression is involved in cell-to-cell fusion when coexpressed with the viral fusion protein F or coexpressed with F and the receptor-binding protein G. This work may define a separate class of viral proteins that promote cell-to-cell fusion.
Gender contributes to personal research funding success in The Netherlands
Authors: van der Lee Romy , Ellemers Naomi 
Published: September 2015

Significance
Women remain underrepresented in academia as they continue to face a leadership gap, salary gap, and funding gap. Closing the funding gap is of particular importance, because this may directly retain women in academia and foster the closing of other gaps. In this study, we examined the grant funding rates of a national full population of early career scientists. Our results reveal gender bias favoring male applicants over female applicants in the prioritization of their “quality of researcher” (but not “quality of proposal”) evaluations and success rates, as well as in the language use in instructional and evaluation materials. This work illuminates how and when the funding gap and the subsequent underrepresentation of women in academia are perpetuated.