bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are There Multiple Kinds of Episodic Memory? An fMRI Investigation Comparing Autobiographical and Recognition Memory Tasks
Authors: Chen Hung-Yu , Gilmore Adrian W. , Nelson Steven M. , McDermott Kathleen B. 
Published: February 2017

What brain regions underlie retrieval from episodic memory? The bulk of research addressing this question with fMRI has relied upon recognition memory for materials encoded within the laboratory. Another, less dominant tradition has used autobiographical methods, whereby people recall events from their lifetime, often after being cued with words or pictures. The current study addresses how the neural substrates of successful memory retrieval differed as a function of the targeted memory when the experimental parameters were held constant in the two conditions (except for instructions). Human participants studied a set of scenes and then took two types of memory test while undergoing fMRI scanning. In one condition (the picture memory test), participants reported for each scene (32 studied, 64 nonstudied) whether it was recollected from the prior study episode. In a second condition (the life memory test), participants reported for each scene (32 studied, 64 nonstudied) whether it reminded them of a specific event from their preexperimental lifetime. An examination of successful retrieval (yes responses) for recently studied scenes for the two test types revealed pronounced differences; that is, autobiographical retrieval instantiated with the life memory test preferentially activated the default mode network, whereas hits in the picture memory test preferentially engaged the parietal memory network as well as portions of the frontoparietal control network. When experimental cueing parameters are held constant, the neural underpinnings of successful memory retrieval differ when remembering life events and recently learned events.SIGNIFICANCE STATEMENTEpisodic memory is often discussed as a solitary construct. However, experimental traditions examining episodic memory use very different approaches, and these are rarely compared to one another. When the neural correlates associated with each approach have been directly contrasted, results have varied considerably and at times contradicted each other. The present experiment was designed to match the two primary approaches to studying episodic memory in an unparalleled manner. Results suggest a clear separation of systems supporting memory as it is typically tested in the laboratory and memory as assessed under autobiographical retrieval conditions. These data provide neurobiological evidence that episodic memory is not a single construct, challenging the degree to which different experimental traditions are studying the same construct.
The variation in free 25-hydroxy vitamin D and vitamin D-binding protein with season and vitamin D status
Authors: Oleröd Göran , Hultén Lillemor Mattsson , Hammarsten Ola , Klingberg Eva 
Published: February 2017

Purpose
Serum 25-hydroxy vitamin D [25(OH)D] varies greatly with season at northern latitudes. The purpose of this study was to determine if the seasonal variations in serum total 25(OH)D are followed by a concomitant variation in free 25(OH)D or if the variation is damped by alterations in the binding capacity of DBP.

Methods
Serum was collected from 540 healthy blood donors (60% men; mean age 41 ± 13 years) during 12 months and analyzed for total 25(OH)D, directly measured free 25(OH)D, vitamin D-binding protein (DBP) and albumin. Calculated free 25(OH)D was estimated.

Results
The UV-B radiation during the sampling month was positively correlated with the serum levels of total 25(OH)D (r = 0.355, P < 0.001), directly measured free (r = 0.336, P < 0.001) and calculated free 25(OH)D (r = 0.275, P < 0.001), but not with DBP and albumin. The percentage of free 25(OH)D was higher during the winter months than that during the summer months (0.020 ± 0.005% vs 0.019 ± 0.004%; P = 0.007) and higher in participants with a serum 25(OH)D below 25 nmol/L than that in participants with a serum 25(OH)D above 75 nmol/L (0.031 ± 0.007% vs 0.017 ± 0.003%; P < 0.001). iPTH was correlated with directly measured free 25(OH)D (r = −0.226; P < 0.001), but only weakly with calculated free 25(OH)D (r = −0.095; P = 0.027).

Conclusions
Directly measured free serum 25(OH)D was highly correlated with total serum 25(OH)D and followed the same seasonal variation, whereas the serum concentrations of DBP and albumin were stable. The fluctuation in free 25(OH)D was only marginally damped with an increase in the percentage of free 25(OH)D during the winter months and in participants with vitamin D deficiency.
Prevalence, incidence and associated comorbidities of treated hypothyroidism: an update from a European population
Authors: Giorda Carlo B , Carnà Paolo , Romeo Francesco , Costa Giuseppe , Tartaglino Barbara , Gnavi Roberto 
Published: February 2017

Objective
Estimates of the prevalence of hypothyroidism in unselected populations date from the late 1990s. We present an update on the prevalence and incidence of overt hypothyroidism in Piedmont, northwest Italy and examine the association between hypothyroidism and multiple chronic comorbidities.

Design and methods
Data were obtained from drug prescription and hospital discharge databases. Individuals who had received at least two levothyroxine prescriptions in 2012 were defined as having hypothyroidism; those who had undergone thyroidectomy or I131 irradiation in the previous 5 years were defined as having iatrogenic hypothyroidism and those who had either obtained exemption from treatment co-payment or had been discharged from hospital with a chronic comorbidity (diabetes and connective tissue diseases) were identified as having one of these conditions.

Results
The overall crude prevalence was 31.1/1000 (2.3/1000 for iatrogenic hypothyroidism) and the overall crude incidence was 7/1000. The average daily dose of thyroxine (122 µg) roughly corresponded to 1.7 µg/kg. There was a strong association between hypothyroidism and diabetes (type 1, type 2 or gestational) and with autoimmune diseases, with the odds ratio ranging from 1.43 (1.02–1.99) for psoriatic arthritis to 4.99 (3.06–8.15) for lupus erythematosus.

Conclusions
As compared with previous estimates, the prevalence of hypothyroidism rose by about 35%, driven mainly by non-iatrogenic forms. The increase may be due to either population aging or improved diagnostic capability or both. The frequent co-occurrence of hypothyroidism with other multiple chronic conditions characterizes it more as a comorbidity rather than an isolated chronic disease.
Comparative Analysis of Satellite DNA in theDrosophila melanogasterSpecies Complex
Authors: Jagannathan Madhav , Warsinger-Pepe Natalie , Watase George J , Yamashita Yukiko M 
Published: February 2017

AbstractSatellite DNAs are highly repetitive sequences that account for the majority of constitutive heterochromatin in many eukaryotic genomes. It is widely recognized that sequences and locations of satellite DNAs are highly divergent even in closely related species, contributing to the hypothesis that satellite DNA differences may underlie speciation. However, due to its repetitive nature, the mapping of satellite DNAs has been mostly left out of recent genomics analyses, hampering the use of molecular genetics techniques to better understand their role in speciation and evolution. Satellite DNAs are most extensively and comprehensively mapped in Drosophila melanogaster, a species that is also an excellent model system with which to study speciation. Yet the lack of comprehensive knowledge regarding satellite DNA identity and location in its sibling species (D. simulans, D. mauritiana, and D. sechellia) has prevented the full utilization of D. melanogaster in studying speciation. To overcome this problem, we initiated the mapping of satellite DNAs on the genomes of the D. melanogaster species complex (D. melanogaster, D. simulans, D. mauritiana, and D. sechellia) using multi-color fluorescent in situ hybridization (FISH) probes. Our study confirms a striking divergence of satellite DNAs in the D. melanogaster species complex, even among the closely related species of the D. simulans clade (D. simulans, D. mauritiana, and D. sechellia), and suggests the presence of unidentified satellite sequences in these species.
Predictability of Genetic Interactions from Functional Gene Modules
Authors: Young Jonathan H , Marcotte Edward M 
Published: February 2017

AbstractCharacterizing genetic interactions is crucial to understanding cellular and organismal response to gene-level perturbations. Such knowledge can inform the selection of candidate disease therapy targets, yet experimentally determining whether genes interact is technically nontrivial and time-consuming. High-fidelity prediction of different classes of genetic interactions in multiple organisms would substantially alleviate this experimental burden. Under the hypothesis that functionally related genes tend to share common genetic interaction partners, we evaluate a computational approach to predict genetic interactions in Homo sapiens, Drosophila melanogaster, and Saccharomyces cerevisiae. By leveraging knowledge of functional relationships between genes, we cross-validate predictions on known genetic interactions and observe high predictive power of multiple classes of genetic interactions in all three organisms. Additionally, our method suggests high-confidence candidate interaction pairs that can be directly experimentally tested. A web application is provided for users to query genes for predicted novel genetic interaction partners. Finally, by subsampling the known yeast genetic interaction network, we found that novel genetic interactions are predictable even when knowledge of currently known interactions is minimal.
Paralog-Specific Functions ofRPL7AandRPL7BMediated by Ribosomal Protein or snoRNA Dosage inSaccharomyces cerevisiae
Authors: Palumbo Ryan J , Fuchs Gabriele , Lutz Sheila , Curcio M Joan 
Published: February 2017

AbstractMost ribosomal proteins in Saccharomyces cerevisiae are encoded by two paralogs that additively produce the optimal protein level for cell growth. Nonetheless, deleting one paralog of most ribosomal protein gene pairs results in a variety of phenotypes not observed when the other paralog is deleted. To determine whether paralog-specific phenotypes associated with deleting RPL7A or RPL7B stem from distinct functions or different levels of the encoded isoforms, the coding region and introns of one paralog, including an intron-embedded snoRNA (small nucleolar RNA) gene, were exchanged with that of the other paralog. Among mutants harboring a single native or chimeric RPL7 allele, expression from the RPL7A locus exceeded that from the RPL7B locus, and more Rpl7a was expressed from either locus than Rpl7b. Phenotypic differences in tunicamycin sensitivity, ASH1 mRNA localization, and mobility of the Ty1 retrotransposon were strongly correlated with Rpl7 and ribosome levels, but not with the Rpl7 or snoRNA isoform expressed. Although Ty1 RNA is cotranslationally localized, depletion of Rpl7 minimally affected synthesis of Ty1 Gag protein, but strongly influenced Ty1 RNA localization. Unlike the other processes studied, Ty1 cDNA accumulation was influenced by both the level and isoform of Rpl7 or snoRNA expressed. These cellular processes had different minimal threshold values for Rpl7 and ribosome levels, but all were functional when isoforms of either paralog were expressed from the RPL7A locus or both RPL7 loci. This study illustrates the broad range of phenotypes that can result from depleting ribosomes to different levels.
Genomics of Compensatory Adaptation in Experimental Populations of Aspergillus nidulans
Authors: Dettman Jeremy R , Rodrigue Nicolas , Schoustra Sijmen E , Kassen Rees 
Published: February 2017

Abstract
Knowledge of the number and nature of genetic changes responsible for adaptation is essential for understanding and predicting evolutionary trajectories. Here, we study the genomic basis of compensatory adaptation to the fitness cost of fungicide resistance in experimentally evolved strains of the filamentous fungus Aspergillus nidulans. The original selection experiment tracked the fitness recovery of lines founded by an ancestral strain that was resistant to fludioxonil, but paid a fitness cost in the absence of the fungicide. We obtained whole-genome sequence data for the ancestral A. nidulans strain and eight experimentally evolved strains. We find that fludioxonil resistance in the ancestor was likely conferred by a mutation in histidine kinase nikA, part of the two-component signal transduction system of the high-osmolarity glycerol (HOG) stress response pathway. To compensate for the pleiotropic negative effects of the resistance mutation, the subsequent fitness gains observed in the evolved lines were likely caused by secondary modification of HOG pathway activity. Candidate genes for the compensatory fitness increases were significantly overrepresented by stress response functions, and some were specifically associated with the HOG pathway itself. Parallel evolution at the gene level was rare among evolved lines. There was a positive relationship between the predicted number of adaptive steps, estimated from fitness data, and the number of genomic mutations, determined by whole-genome sequencing. However, the number of genomic mutations was, on average, 8.45 times greater than the number of adaptive steps inferred from fitness data. This research expands our understanding of the genetic basis of adaptation in multicellular eukaryotes and lays out a framework for future work on the genomics of compensatory adaptation in A. nidulans.
Genomic Prediction with Pedigree and Genotype × Environment Interaction in Spring Wheat Grown in South and West Asia, North Africa, and Mexico
Authors: Sukumaran Sivakumar , Crossa Jose , Jarquin Diego , Lopes Marta , Reynolds Matthew P 
Published: February 2017

Abstract
Developing genomic selection (GS) models is an important step in applying GS to accelerate the rate of genetic gain in grain yield in plant breeding. In this study, seven genomic prediction models under two cross-validation (CV) scenarios were tested on 287 advanced elite spring wheat lines phenotyped for grain yield (GY), thousand-grain weight (GW), grain number (GN), and thermal time for flowering (TTF) in 18 international environments (year-location combinations) in major wheat-producing countries in 2010 and 2011. Prediction models with genomic and pedigree information included main effects and interaction with environments. Two random CV schemes were applied to predict a subset of lines that were not observed in any of the 18 environments (CV1), and a subset of lines that were not observed in a set of the environments, but were observed in other environments (CV2). Genomic prediction models, including genotype × environment (G×E) interaction, had the highest average prediction ability under the CV1 scenario for GY (0.31), GN (0.32), GW (0.45), and TTF (0.27). For CV2, the average prediction ability of the model including the interaction terms was generally high for GY (0.38), GN (0.43), GW (0.63), and TTF (0.53). Wheat lines in site-year combinations in Mexico and India had relatively high prediction ability for GY and GW. Results indicated that prediction ability of lines not observed in certain environments could be relatively high for genomic selection when predicting G×E interaction in multi-environment trials.
Genetic Causes of Phenotypic Adaptation to the Second Fermentation of Sparkling Wines inSaccharomyces cerevisiae
Authors: Martí-Raga Maria , Peltier Emilien , Mas Albert , Beltran Gemma , Marullo Philippe 
Published: February 2017

AbstractHybridization is known to improve complex traits due to heterosis and phenotypic robustness. However, these phenomena have been rarely explained at the molecular level. Here, the genetic determinism of Saccharomyces cerevisiae fermentation performance was investigated using a QTL mapping approach on an F1-progeny population. Three main QTL were detected, with positive alleles coming from both parental strains. The heterosis effect found in the hybrid was partially explained by three loci showing pseudooverdominance and dominance effects. The molecular dissection of those QTL revealed that the adaptation to second fermentation is related to pH, lipid, or osmotic regulation. Our results suggest that the stressful conditions of second fermentation have driven the selection of rare genetic variants adapted to maintain yeast cell homeostasis and, in particular, to low pH conditions.
Transcriptome Analysis ofDrosophila melanogasterThird Instar Larval Ring Glands Points to Novel Functions and Uncovers a Cytochrome p450 Required for Development
Authors: Christesen Danielle , Yang Ying Ting , Somers Jason , Robin Charles , Sztal Tamar , Batterham Philip , Perry Trent 
Published: February 2017

AbstractIn Drosophila melanogaster larvae, the ring gland (RG) is a control center that orchestrates major developmental transitions. It is a composite organ, consisting of the prothoracic gland, the corpus allatum, and the corpora cardiaca, each of which synthesizes and secretes a different hormone. Until now, the RG’s broader developmental roles beyond endocrine secretion have not been explored. RNA sequencing and analysis of a new transcriptome resource from D. melanogaster wandering third instar larval RGs has provided a fascinating insight into the diversity of developmental signaling in this organ. We have found strong enrichment of expression of two gene pathways not previously associated with the RG: immune response and fatty acid metabolism. We have also uncovered strong expression for many uncharacterized genes. Additionally, RNA interference against RG-enriched cytochrome p450s Cyp6u1 and Cyp6g2 produced a lethal ecdysone deficiency and a juvenile hormone deficiency, respectively, flagging a critical role for these genes in hormone synthesis. This transcriptome provides a valuable new resource for investigation of roles played by the RG in governing insect development.
A Network of Chromatin Factors Is Regulating the Transition to Postembryonic Development inCaenorhabditis elegans
Authors: Erdelyi Peter , Wang Xing , Suleski Marina , Wicky Chantal 
Published: February 2017

AbstractMi2 proteins are evolutionarily conserved, ATP-dependent chromatin remodelers of the CHD family that play key roles in stem cell differentiation and reprogramming. In Caenorhabditis elegans, the let-418 gene encodes one of the two Mi2 homologs, which is part of at least two chromatin complexes, namely the Nucleosome Remodeling and histone Deacetylase (NuRD) complex and the MEC complex, and functions in larval development, vulval morphogenesis, lifespan regulation, and cell fate determination. To explore the mechanisms involved in the action of LET-418/Mi2, we performed a genome-wide RNA interference (RNAi) screen for suppressors of early larval arrest associated with let-418 mutations. We identified 29 suppressor genes, of which 24 encode chromatin regulators, mostly orthologs of proteins present in transcriptional activator complexes. The remaining five genes vary broadly in their predicted functions. All suppressor genes could suppress multiple aspects of the let-418 phenotype, including developmental arrest and ectopic expression of germline genes in the soma. Analysis of available transcriptomic data and quantitative PCR revealed that LET-418 and the suppressors of early larval arrest are regulating common target genes. These suppressors might represent direct competitors of LET-418 complexes for chromatin regulation of crucial genes involved in the transition to postembryonic development.
upSET, the Drosophila homologue of SET3, Is Required for Viability and the Proper Balance of Active and Repressive Chromatin Marks
Authors: McElroy Kyle A , Jung Youngsook L , Zee Barry M , Wang Charlotte I , Park Peter J , Kuroda Mitzi I 
Published: February 2017

Abstract
Chromatin plays a critical role in faithful implementation of gene expression programs. Different post-translational modifications (PTMs) of histone proteins reflect the underlying state of gene activity, and many chromatin proteins write, erase, bind, or are repelled by, these histone marks. One such protein is UpSET, the Drosophila homolog of yeast Set3 and mammalian KMT2E (MLL5). Here, we show that UpSET is necessary for the proper balance between active and repressed states. Using CRISPR/Cas-9 editing, we generated S2 cells that are mutant for upSET. We found that loss of UpSET is tolerated in S2 cells, but that heterochromatin is misregulated, as evidenced by a strong decrease in H3K9me2 levels assessed by bulk histone PTM quantification. To test whether this finding was consistent in the whole organism, we deleted the upSET coding sequence using CRISPR/Cas-9, which we found to be lethal in both sexes in flies. We were able to rescue this lethality using a tagged upSET transgene, and found that UpSET protein localizes to transcriptional start sites (TSS) of active genes throughout the genome. Misregulated heterochromatin is apparent by suppressed position effect variegation of the wm4 allele in heterozygous upSET-deleted flies. Using nascent-RNA sequencing in the upSET-mutant S2 lines, we show that this result applies to heterochromatin genes generally. Our findings support a critical role for UpSET in maintaining heterochromatin, perhaps by delimiting the active chromatin environment.
The Nuclear Cap-Binding Complex Mediates Meiotic Silencing by Unpaired DNA
Authors: Decker Logan M , Xiao Hua , Boone Erin C , Vierling Michael M , Shanker Benjamin S , Kingston Shanika L , Boone Shannon F , Haynes Jackson B , Shiu Patrick K T 
Published: February 2017

AbstractIn the filamentous fungus Neurospora crassa, cross walls between individual cells are normally incomplete, making the entire fungal network vulnerable to attack by viruses and selfish DNAs. Accordingly, several genome surveillance mechanisms are maintained to help the fungus combat these repetitive elements. One of these defense mechanisms is called meiotic silencing by unpaired DNA (MSUD), which identifies and silences unpaired genes during meiosis. Utilizing common RNA interference (RNAi) proteins, such as Dicer and Argonaute, MSUD targets mRNAs homologous to the unpaired sequence to achieve silencing. In this study, we have identified an additional silencing component, namely the cap-binding complex (CBC). Made up of cap-binding proteins CBP20 and CBP80, CBC associates with the 5′ cap of mRNA transcripts in eukaryotes. The loss of CBC leads to a deficiency in MSUD activity, suggesting its role in mediating silencing. As confirmed in this study, CBC is predominantly nuclear, although it is known to travel in and out of the nucleus to facilitate RNA transport. As seen in animals but not in plants, CBP20’s robust nuclear import depends on CBP80 in Neurospora. CBC interacts with a component (Argonaute) of the perinuclear meiotic silencing complex (MSC), directly linking the two cellular factors.