bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contributions of hippocampus and striatum to memory-guided behavior depend on past experience
Authors: Ferbinteanu Janina 
Published: February 2016

ABSTRACTThe hippocampal and striatal memory systems operate independently and in parallel in supporting spatial and response learning, respectively, when animals are explicitly trained in one task. Here, we investigated whether this principle continues to hold when animals are concurrently trained in two types of tasks. Rats were trained on a plus maze in either a spatial navigation or a cue response task (individual training), while a third set of rats acquired both (concurrent training). Subsequently, the rats underwent either sham surgery or neurotoxic lesions of the hippocampus (HPC), medial dorsal striatum (DSM) or lateral dorsal striatum (DSL), followed by retention testing. Finally, rats in the individual training condition also acquired the novel ‘other’ task. When rats learned one task, HPC and DSL selectively supported spatial navigation cue response, respectively. However, when rats learned both tasks, HPC and DSL additionally supported the behavior incongruent with the processing style of the corresponding memory system. DSM significantly contributed to performance regardless of task or training procedure. Experience with the cue response task facilitated subsequent spatial learning, while experience with spatial navigation delayed both simultaneous and subsequent response learning. These findings suggest that multiple principles govern the interactions among memory systems.Significance StatementCurrently, we distinguish among several types of memories, each supported by a distinct neural circuit. The memory systems are thought to operate independently and in parallel. Here, we demonstrate that the hippocampus and the dorsal striatum memory systems indeed operate independently and in parallel when rats learn one type of task at a time, but interact co-operatively and in synergism when rats concurrently learn two types of tasks. Furthermore, new learning is modulated by past experiences. These results can be explained by a model in which independent and parallel information processing that occurs in the separate memory-related neural circuits is supplemented by information transfer between the memory systems at the level of the cortex.
Recurrent selection explains parallel evolution of genomic regions of high relative but low absolute differentiation in greenish warblers
Authors: Irwin Darren E. , Alcaide Miguel , Delmore Kira E. , Irwin Jessica H. , Owens Gregory L. 
Published: February 2016

AbstractRecent technological developments allow investigation of the repeatability of evolution at the genomic level. Such investigation is particularly powerful when applied to a ring species, in which spatial variation represents changes during the evolution of two species from one. We examined genomic variation among three subspecies of the greenish warbler ring species, using genotypes at 13,013,950 nucleotide sites along a new greenish warbler consensus genome assembly. Genomic regions of low within-group variation are remarkably consistent between the three populations. These regions show high relative differentiation but low absolute differentiation between populations. Comparisons with outgroup species show the locations of these peaks of relative differentiation are not well explained by phylogenetically-conserved variation in recombination rates or selection. These patterns are consistent with a model in which selection in an ancestral form has reduced variation at some parts of the genome, and those same regions experience recurrent selection that subsequently reduces variation within each subspecies. The degree of heterogeneity in nucleotide diversity is greater than explained by models background selection, but are consistent with selective sweeps. Given the evidence that greenish warblers have had both population differentiation for a long period of time and periods of gene flow between those populations, we propose that some genomic regions underwent selective sweeps over a broad geographic area followed by within-population selection-induced reductions in variation. An important implication of this “sweep-before-differentiation” model is that genomic regions of high relative differentiation may have moved among populations more recently than other genomic regions.
Genomic prediction of coronary heart disease
Authors: Abraham Gad , Havulinna Aki S. , Bhalala Oneil G. , Byars Sean G. , De Livera Alysha M. , Yetukuri Laxman , Tikkanen Emmi , Perola Markus , Schunkert Heribert , Sijbrands Eric J. , Palotie Aarno , Samani Nilesh J. , Salomaa Veikko , Ripatti Samuli , Inouye Michael 
Published: February 2016

AbstractBackgroundGenetics plays an important role in coronary heart disease (CHD) but the clinical utility of a genomic risk score (GRS) relative to clinical risk scores, such as the Framingham Risk Score (FRS), is unclear.MethodsWe generated a GRS of 49,310 SNPs based on a CARDIoGRAMplusC4D Consortium meta-analysis of CHD, then independently tested this using five prospective population cohorts (three FINRISK cohorts, combined n=12,676, 757 incident CHD events; two Framingham Heart Study cohorts (FHS), combined n=3,406, 587 incident CHD events).ResultsThe GRS was strongly associated with time to CHD event (FINRISK HR=1.74, 95% CI 1.61-1.86 per S.D. of GRS; Framingham HR=1.28, 95% CI 1.18-1.38), and was largely unchanged by adjustment for clinical risk scores or individual risk factors, including family history. Integration of the GRS with clinical risk scores (FRS and ACC/AHA13 score) improved prediction of CHD events within 10 years (meta-analysis C-index: +1.5-1.6%,P<0.001), particularly for individuals ≥60 years old (meta-analysis C-index: +4.6-5.1%,P<0.001). Men in the top 20% of the GRS had 3-fold higher risk of CHD by age 75 in FINRISK and 2-fold in FHS, and attaining 10% cumulative CHD risk 18y earlier in FINRISK and 12y earlier in FHS than those in the bottom 20%. Furthermore, high genomic risk was partially compensated for by low systolic blood pressure, low cholesterol level, and non-smoking.ConclusionsA GRS based on a large number of SNPs substantially improves CHD risk prediction and encodes decades of variation in CHD risk not captured by traditional clinical risk scores.
Increased pollination specialization did not increase corolla shape constraints in Antillean plants
Authors: Joly Simon , Lambert François , Alexandre Hermine , Clavel Julien , Léveillé-Bourret Étienne , Clark John L. 
Published: February 2016

AbstractFlowers show important structural variation as reproductive organs but the evolutionary forces underlying this diversity are still poorly understood. In animal-pollinated species, flower shape is strongly fashioned by selection imposed by pollinators, which is expected to vary according to guilds of effective pollinators. Using the Antillean subtribe Gesneriinae (Gesneriaceae), we tested the hypothesis that pollination specialists pollinated by one functional type of pollinator have maintained more similar corolla shapes through time due to stronger selection constraints compared to species with more generalist pollination strategies. Using geometric morphometrics and evolutionary models, we showed that the corolla of hummingbird specialists, bat specialists, and species with a mixed-pollination strategy (pollinated by hummingbirds and bats; thus a more generalist strategy) have distinct shapes and that these shapes have evolved under evolutionary constraints. However, we did not find support for smaller disparity in corolla shape for hummingbird specialists compared to more generalist species. This could be because the corolla shape of more generalist species in subtribe Gesneriinae, which has evolved multiple times, is finely adapted to be effectively pollinated by both bats and hummingbirds. These results suggest that pollination generalization is not necessarily associated with relaxed selection constraints.
Cell fate-decision as high-dimensional critical state transition
Authors: Mojtahedi Mitra , Skupin Alexander , Zhou Joseph , Castaño Ivan G. , Leong-Quong Rebecca Y. Y. , Chang Hannah , Giuliani Alessandro , Huang Sui 
Published: February 2016

AbstractCell fate choice and commitment of multipotent progenitor cells to a differentiated lineage requires broad changes of their gene expression profile. However, how progenitor cells overcome the stability of their robust gene expression configuration (attractor) and exit their state remains elusive. Here we show that commitment of blood progenitor cells to the erythroid or the myeloid lineage is preceded by the destabilization of their high-dimensional attractor state and that cells undergo a critical state transition. Single-cell resolution analysis of gene expression in populations of differentiating cells affords a new quantitative index for predicting critical transitions in a high-dimensional state space: decrease of correlation between cells with concomitant increase of correlation between genes as cells approach a tipping point. The detection of “rebellious cells” which enter the fate opposite to the one intended corroborates the model of preceding destabilization of the progenitor state. Thus, “early-warning signals” associated with critical transitions can be detected in statistical ensembles of high-dimensional systems, offering a formal tool for analyzing single-cell’s molecular profiles that goes beyond computational pattern recognition but is based on dynamical systems theory and can predict impending major shifts in cell populations in development and disease.
Socially mediated effects of climate change decrease survival of hibernating Alpine marmots
Authors: Rézouki Célia , Tafani Marion , Cohas Aurélie , Loison Anne , Gaillard Jean‐Michel , Allainé Dominique , Bonenfant Christophe 
Published: February 2016

Summary

In the context of global change, an increasing challenge is to understand the interaction between weather variables and life histories. Species‐specific life histories should condition the way climate influences population dynamics, particularly those that are associated with environmental constraints, such as lifestyles like hibernation and sociality. However, the influence of lifestyle in the response of organisms to climate change remains poorly understood.

Based on a 23‐year longitudinal study on Alpine marmots, we investigated how their lifestyle, characterized by a long hibernation and a high degree of sociality, interacts with the ongoing climate change to shape temporal variation in age‐specific survival.

As generally reported in other hibernating species, we expected survival of Alpine marmots to be affected by the continuous lengthening of the growing season of plants more than by changes in winter conditions. We found, however, that Alpine marmots displayed lower juvenile survival over time. Colder winters associated with a thinner snow layer lowered juvenile survival, which in turn was associated with a decrease in the relative number of helpers in groups the following years, and therefore lowered the chances of over‐winter survival of juveniles born in the most recent years.

Our results provide evidence that constraints on life‐history traits associated with hibernation and sociality caused juvenile survival to decrease over time, which might prevent Alpine marmots coping successfully with climate change.
Neighbour Effects in the Provision of Public Goods in a Young Democracy: Evidence from China
Authors: Agostini Claudio A. , Brown Philip , Zhang Xiaobo 
Published: February 2016

AbstractFiscal mimicking and yardstick competition among neighbouring jurisdictions have been widely documented in developed countries with long histories of democracy. However, there is very little empirical evidence concerning these practices in developing countries with young democracies. Using a primary panel of 86 rural Chinese administrative villages that have undergone transitions to democracy over the past two decades, we show that the neighbourhood effect also exists in a young democracy, albeit at a lower magnitude than in a mature democracy. Elected chairs of village committees who have served more than one term respond positively to the provision of public projects in neighbouring villages by increasing both the number of public projects and the funding allocated to undertake them. In contrast, appointed party secretaries with more than 1 year of service are insensitive to neighbours' performance. In addition, village leaders are strategic in timing the arrival of public projects to increase the probability of re‐election: in the year preceding elections, both the number and budget of public projects increase significantly. In this sense, politicians in young and old democracies behave alike.
China's Global Influence: A Survey through the Lens of International Trade
Authors: Qiu Larry D. , Zhan Chaoqun 
Published: February 2016

AbstractOne of the most impressive changes in the global economy in the past half‐century has been China's high and sustained growth and its integration into the global economy. This phenomenal change not only brings huge benefits to the Chinese people, but also exerts a tremendous influence on the rest of the world. How large is China's influence on the global economy? How are various countries/regions affected differently? How are various industries in a country affected differently? Answering these questions is not simple. In this paper, we review the recent literature that attempts to answer these questions. The findings of the survey conducted in this study aim to provide a complete picture of China's global influence and to identify issues that require further analysis.
Outward Direct Investment, Firm Productivity and Credit Constraints: Evidence from Chinese Firms
Authors: Wang Bijun , Tan Yuyan , Yu Miaojie , Huang Yiping 
Published: February 2016

AbstractChina is currently the third largest country in terms of outward direct investment (ODI), with the investors mainly being state‐owned enterprises. This presents a question: What inhibits private enterprises from increasing ODI? Using a firm‐level panel data set for Zhejiang Province in China, we examine the impact of firm heterogeneity on private firm ODI. We have three main findings: first, a higher productivity level contributes to better access to ODI, and increases ODI value as well; second, lowering a firm's financial constraint level can increase both the probability and volume of ODI; third, productivity cannot offset the negative effect of financial constraint on private firm ODI.
The pregnane X receptor down‐regulates organic cation transporter 1 (SLC22A1) in human hepatocytes by competing for (“squelching”) SRC‐1 coactivator
Authors: Hyrsova Lucie , Smutny Tomas , Carazo Alejandro , Moravcik Stefan , Mandikova Jana , Trejtnar Frantisek , Gerbal‐Chaloin Sabine , Pavek Petr 
Published: February 2016

Background and PurposeThe organic cation transporter 1 (OCT1) transports cationic drugs into hepatocytes. The high hepatic expression of OCT1 is controlled by the HNF4α and USF transcription factors. Pregnane X receptor (PXR) mediates induction of the principal xenobiotic metabolizing enzymes and transporters in the liver. Here, we have assessed the down‐regulation of OCT1 expression by PXR activation.Experimental ApproachWe used primary human hepatocytes and related cell lines to measure OCT1 expression and activity, by assaying MPP+ accumulation. Western blotting, qRT‐PCR, the OCT1 promoter gene reporter constructs and chromatin immunoprecipitation assays were also used.Key ResultsOCT1 mRNA in human hepatocytes was down‐regulated along with reduced [3H]MPP+ accumulation in differentiated HepaRG cells after treatment with rifampicin. Rifampicin and hyperforin as well as the constitutively active PXR mutant T248D suppressed activity of the 1.8 kb OCT1 promoter construct in gene reporter assays. Silencing of both PXR and HNF4α in HepaRG cells blocked the PXR ligand‐mediated down‐regulation of OCT1 expression. The mutation of HNF4α and USF1 (E‐box) responsive elements reversed the PXR‐mediated inhibition in gene reporter assays. Chromatin immunoprecipitation assays indicated that PXR activation sequestrates the SRC‐1 coactivator from the HNF4α response element and E‐box of the OCT1 promoter. Consistent with these findings, exogenous overexpression of the SRC‐1, but not the PGC1α coactivator, relieved the PXR‐mediated repression of OCT1 transactivation.Conclusions and ImplicationsPXR ligands reduced the HNF4α‐mediated and USF‐mediated transactivation of OCT1 gene expression by competing for SRC‐1 and decreased delivery of a model OCT1 substrate into hepatocytes.
Phase I study of a new cancer vaccine of ten mixed peptides for advanced cancer patients
Authors: Iwasa Satoru , Yamada Yasuhide , Heike Yuji , Shoji Hirokazu , Honma Yoshitaka , Komatsu Nobukazu , Matsueda Satoko , Yamada Akira , Morita Michi , Yamaguchi Rin , Tanaka Natsuki , Kawahara Akihiko , Kage Masayoshi , Shichijo Shigeki , Sasada Tetsuro , Itoh Kyogo 
Published: February 2016

A phase I study of a new cancer vaccine (KRM‐10), consisting of a mixture of 10 different short peptides, was conducted for patients with advanced gastrointestinal cancers. Primary or secondary endpoints included the dose‐limiting toxicity (DLT), or safety and immune responses, respectively. Peptide‐specific cytotoxic T lymphocytes (CTL) and immunoglobulin G (IgG), together with soluble inflammatory factors, were measured before and after vaccination. Twenty‐one patients were vaccinated with KRM‐10 at dose levels of 10 (n = 6), 20 (n = 8) or 30 mg (n = 7) of peptides every week for 6 weeks. No DLT were observed in the dose range evaluated. Common treatment‐related adverse events were a grade 1 injection site reaction in 15 patients, and fever in three patients (grade 1 in two patients and grade 2 in one patient). CTL activity to at least one peptide at the time of the third and sixth vaccination increased in 2 and 3 of 6 (10 mg), 2 of 8 and 4 of 6 (20 mg), or 2 and 1 of 6 (30 mg) patients, respectively. IgG levels, at the third and sixth vaccination, were also increased in 1 and 1 of 6 (10 mg), 2 of 8 and 4 of 6 (20 mg), or 1 and 3 of 6 (30 mg) patients, respectively. The KRM‐10 vaccine consisting of 20 mg of peptides was determined as the optimal dose for a coming phase II trial because of its safety, and also for demonstrating the most potent activity for augmenting the immune response of the three doses tested. This trial was registered at the UMIN Clinical Trials Registry as UMIN000008820.
Ridge Preservation Using Composite Alloplastic Materials: A Randomized Control Clinical and Histological Study in Humans
Authors: Mayer Yaniv , Zigdon‐Giladi Hadar , Machtei Eli E. 
Published: February 2016

AbstractAimTo evaluate (clinically, histologically, and histo‐morphometrically) the use of composite materials (Biphasic calcium sulphate [BCS] with β Tri‐Calcium Phosphate (β‐TCP) and Hydroxyapatite [HA]) in extraction socket sites and compare it to un‐disturbed natural healing.Material and MethodsProspective clinical trial of 36 patients (40 extraction sockets) were randomly assigned to either test or control group. Alveolar ridge horizontal dimension was measured in the middle of the socket at crest and 3 and 6 mm subcrestally. Crestal vertical height was measured at baseline surgery and at 4 month re‐entry, at which time bone core biopsies were harvested from the center of the edentulous ridge. Histo‐morphometric evaluation of the samples was performed using hematoxylin & eosin stains and morphometric software.ResultsThe change in horizontal ridge width was higher in the control compared to the experimental group: 2.28 ± 2.36 mm versus 0.03 ± 2.32 mm (p = .007) at −3 mm and 2.28 ± 2.43 versus 0.035 ± 3.05 (p = .02) at −6 mm, for the experimental and control sites, respectively. The vertical distance form bone crest to neighboring horizontal line interconnecting the neighboring teeth was minimal in both groups (0.307 ± 2.01 mm versus 0.14 ± 2.03 mm [p = 0.41]). Residual scaffolds occupied 15.99 ± 11.4% of the volume in the grafted (test) sites while bone area fraction was not statistically different among the groups (47.7 ± 10.6% versus 52.6 ± 11.6%, test versus control, respectively p = .39). The percentage of connective tissue in the control group was significantly higher that test group (36.3 ± 19.4% versus 46.7 ± 10.6% test versus control, respectively, p = .013).ConclusionRidge preservation technique using a combination of two synthetic bone grafts β‐TCP and HA with BCS resulted in greater stability in the horizontal dimension after 4 months.
Guided bone regeneration in osteoporotic conditions following treatment with zoledronic acid
Authors: Mardas Nikos , Busetti Juliano , de Figueiredo José Antonio Poli , Mezzomo Luis André , Scarparo Roberta Kochenborger , Donos Nikolaos 
Published: February 2016

AbstractObjectivesTo evaluate new bone formation in calvarial critical size defects (CSD) under dense polytetrafluoroethylene (d‐PTFE), microporous membranes for guided bone regeneration (GBR) in healthy, osteoporotic and osteoporotic treated with zoledronic acid (ZA) rats.MethodsForty‐eight, female, 6‐month old Wistar rats were included in the study. Osteoporosis was induced by ovariectomy (OVX) and calcium‐deficient diet in 32 rats. Sixteen OVX rats were treated with a single dose of Zolendronic Acid (ZA) (OZ), while 16 OVX rats received no treatment (O). The remaining 16 rats were sham‐operated and used as healthy controls (C). At 6 weeks following osteoporosis induction, two 5 mm CSD were created in the parietal bones and one of them was treated with a double d‐PTFE membrane. The healing periods were 30 and 60 days. New bone formation (NB) was assessed by qualitative and quantitative histological analysis.ResultsAfter 30 days of healing, NB (mean% (95% CI)) was 78.9% (21), 93.1% (9.3) and 84.2% (26.9) in the membrane treated defects and 18.8% (24.1), 27.1% (7.9) and 31% (38.8) in the untreated defects of group O, OZ and C, respectively. After 60 days of healing, NB was 78.3% (14.4), 95.8% (9) and 90.1% (26.1) in the membrane treated defects and 10.8% (17.4), 51.6% (39.4) and 15.7% (12.1) in the untreated defects of group O, OZ and C, respectively. Hierarchical analysis of variance showed that treatment with ZA (P = 0.001) and the use of membrane (P = 0.000) significantly increased new bone formation while presence of osteoporosis may have reduced new bone formation (P = 0.028).Conclusiond‐PTFE membranes for GBR promote bone healing in osteoporotic and healthy rats. Treatment with ZA may improve new bone formation in osteoporotic rats.