cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5121439
title: Supplementary Material for: Genome-Wide Gene Expression Analysis of the Switch between Acidogenesis and Solventogenesis in Continuous Cultures of <i>Clostridium acetobutylicum</i>

description: <i>Clostridium acetobutylicum</i> is able to switch from acidogenic growth to solventogenic growth. We used phosphate-limited continuous cultures that established acidogenic growth at pH 5.8 and solventogenic growth at pH 4.5. These cultures allowed a detailed transcriptomic study of the switch from acidogenesis to solventogenesis that is not superimposed by sporulation and other growth phase-dependent parameters. These experiments led to new insights into the physiological role of several genes involved in solvent formation. The <i>adc </i>gene for acetone decarboxylase is upregulated well before the rest of the <i>sol</i> locus during the switch, and pyruvate decarboxylase is induced exclusively for the period of this switch. The aldehyde-alcohol dehydrogenase gene <i>adhE1 </i>located in the <i>sol </i>operon is regulated antagonistically to the paralog <i>adhE2 </i>that is expressed during acidogenic conditions. A similar antagonistic pattern can be seen with the two paralogs of thiolase genes, <i>thlA </i>and <i>thlB</i>. Interestingly, the genes coding for the putative cellulosome in <i>C. acetobutylicum </i>are exclusively transcribed throughout solventogenic growth. The genes for stress response are only induced during the shift but not in the course of solventogenesis when butanol is present in the culture. Finally, the data clearly indicate that solventogenesis is independent from sporulation.
DOI: 10.6084/m9.figshare.5121442
title: Supplementary Material for: A Cost-Effectiveness Analysis of Docetaxel versus Pemetrexed in Second-Line Chemotherapy for Stage IIIb or IV Non-Small Cell Lung Cancer in China

description: <i>Background:</i> To study the cost-efficacy of docetaxel and pemetrexed as single agents versus platinum-based combination agents in second-line treatment of stage IIIb or IV non-small cell lung cancer (NSCLC) patients by evaluating chemotherapeutic indexes and medical costs. <i>Methods:</i> Treatment responses were evaluated by progression-free survival (PFS), overall survival (OS), hematological and gastrointestinal toxicities. <i>Results:</i> Two hundred and seven stage IIIb or IV NSCLC patients were recruited to this clinical observation retrospective study. Thirty-four subjects were treated with docetaxel (group A), 98 with platinum-based doublet chemotherapy with docetaxel (group B), 42 with pemetrexed (group C), and 33 patients with platinum-based doublet combination therapy with pemetrexed (group D). The average PFS of groups A and B was 3.28 and 4.58 months, respectively (p = 0.042). The mean PFS of groups C and D was 3.1 and 4.98 months, respectively (p = 0.017). The mean OS of these groups was 12.88, 13.17, 12.40 and 13.04 months, respectively, without significant differences. The total medical costs in these four groups amounted to USD 5,533, 7,745, 8,569 and 15,291, respectively. <i>Conclusions:</i> Platinum-based doublet chemotherapy with docetaxel or pemetrexed could significantly increase PFS, however, without significant OS improvement in comparison with using them as single agents. The medical expenses associated with doublet therapy were much higher than those associated with single therapy with a significant portion of the medical expenses spent on treating hematological and gastrointestinal toxicity.
DOI: 10.6084/m9.figshare.5121445
title: Supplementary Material for: Effects of Estrogen on Beta-Amyloid-Induced Cholinergic Cell Death in the Nucleus Basalis Magnocellularis

description: Alzheimer disease is characterized by accumulation of β-amyloid (Aβ) and cognitive dysfunctions linked to early loss of cholinergic neurons. As estrogen-based hormone replacement therapy has beneficial effects on cognition of demented patients, and it may prevent memory impairments, we investigated the effect of estrogen-pretreatment on Aβ-induced cholinergic neurodegeneration in the nucleus basalis magnocellularis (NBM). We tested which Aβ species induces the more pronounced cholinotoxic effect in vivo. We injected different Aβ assemblies in the NBM of mice, and measured cholinergic cell and cortical fiber loss. Spherical Aβ oligomers had the most toxic effect. Pretreatment of ovariectomized mice with estrogen before Aβ injection decreased cholinergic neuron loss and partly prevented fiber degeneration. By using proteomics, we searched for proteins involved in estrogen-mediated protection and in Aβ toxicity 24 h following injection. The change in expression of, e.g., DJ-1, NADH ubiquinone oxidoreductase, ATP synthase, phosphatidylethanolamine-binding protein 1, protein phosphatase 2A and dimethylarginine dimethylaminohydrolase 1 support our hypothesis that Aβ induces mitochondrial dysfunction, decreases MAPK signaling, and increases NOS activation in NBM. On the other hand, altered expression of, e.g., MAP kinase kinase 1 and 2, protein phosphatase 1 and 2A by Aβ might increase MAPK suppression and NOS signaling in the cortical target area. Estrogen pretreatment reversed most of the changes in the proteome in both areas. Our experiments suggest that regulation of the MAPK pathway, mitochondrial pH and NO production may all contribute to Aβ toxicity, and their regulation can be prevented partly by estrogen pretreatment.
DOI: 10.6084/m9.figshare.5121448.v1
title: Supplementary Material for: Validated Methods of Cough Assessment: A Systematic Review of the Literature

description: <i>Background:</i> Cough is a common symptom for which patients often seek medical advice and consume vast amounts of drugs. It is a real challenge for both the physician and the clinical researcher to evaluate a cough’s clinical importance and its precise response to treatment. <i>Objectives:</i> This systematic literature review has the following objectives: first, to make an inventory of the validated tools for assessing cough, and second, to investigate the extent to which the results of various assessment methods can be correlated. <i>Methods:</i> Two independent investigators searched the Medline, Embase, and Cochrane databases for validation studies on cough assessment tools. <i>Results:</i> Thirty-four studies were included. Several ambulatory cough monitors automatically identify cough and have been validated in a limited number of patients. Three cough-specific quality-of-life scales (Leicester Cough Questionnaire, Cough Quality of Life Questionnaire, and Burden of Cough Questionnaire) have been validated. No validation studies of descriptive scores or visual analogue scales were found. The correlations between quality-of-life scores and cough frequency were good. The correlations between descriptive scores or visual analogue scales and more objective methods, such as cough frequency monitoring or quality-of-life scores, were inconsistent. <i>Conclusion:</i> Cough-specific quality-of-life questionnaires can provide valid outcomes for research into cough. Although the current developments in cough monitoring devices are promising, further studies on a larger scale, under more realistic conditions, and for different patterns of cough are required before they can be recommended for widespread use.
DOI: 10.6084/m9.figshare.5121457.v1
title: Supplementary Material for: Sex and the Frontal Cortex: A Developmental CT Study in the Spotted Hyena

description: The purpose of this study was to examine developmental and individual variation in total endocranial volume and regional brain volumes, including the anterior cerebrum, posterior cerebrum and cerebellum/brain stem, in the spotted hyena <i>(Crocuta crocuta)</i>. The spotted hyena is a highly gregarious animal noted for living in large, hierarchically organized groups. The social lives of male and female spotted hyenas do not differ until after puberty, when males disperse from the natal group, while females remain philopatric. Here we sought to determine whether the divergent life histories of male and female spotted hyenas are linked to differences in brain size or organization. Three-dimensional virtual endocasts were created using computed tomography from 46 spotted hyenas skulls (23 females, 22 males, 1 unknown sex) ranging in age from 1 day to 18 years. Brain volume and skull length were highly correlated (r = 0.91), and both reached asymptotic values by 34 months of age. Analyses of total endocranial volume (relative to skull length) and cerebellum/brain stem volume (relative to total endocranial volume) revealed no sex differences. However, relative anterior cerebrum volume, comprised mainly of frontal cortex, was significantly greater in adult males than adult females, and relative posterior cerebrum volume was greater in adult females than adult males. We hypothesize that the demands of neural processing underlying enhanced social cognition required for successful male transfer between matriarchical social groups at dispersal may be greater than cognitive demands on philopatric females.
DOI: 10.6084/m9.figshare.5121436
title: Supplementary Material for: Extensive Changes in the Expression of the Opioid Genes between Humans and Chimpanzees

description: The various means by which the body perceives, transmits, and resolves the experiences of pain and nociception are mediated by a host of molecules, including neuropeptides within the opioid gene signaling pathway. The peptide ligands and receptors encoded by this group of genes have been linked to behavioral disorders as well as a number of psychiatric affective disorders. Our aim was to explore the recent evolutionary history of these two gene families by taking a comparative genomics approach, specifically through a comparison between humans and chimpanzees. Our analyses indicate differential expression of these genes between the two species, more than expected based on genome-wide comparisons, indicating that differential expression is pervasive among the opioid genes. Of the 8 family members, three genes showed significant expression differences <i>(PENK</i>, <i>PNOC</i>, and <i>OPRL1)</i>, with two others marginally significant <i>(OPRM1</i> and <i>OPRD1)</i>. Accelerated substitution rates along human and chimpanzee lineages within the putative regulatory regions of <i>OPRM1</i>, <i>POMC</i>, and <i>PDYN</i> between the human and chimpanzee branches are consistent with positive selection. Collectively, these results suggest that there may have been a selective advantage to modulating the expression of the opioid genes in humans compared with our closest living relatives. Information about the cognitive roles mediated by these genes in humans may help to elucidate the trait consequences of these putatively adaptive expression changes.
DOI: 10.6084/m9.figshare.5121442.v1
title: Supplementary Material for: A Cost-Effectiveness Analysis of Docetaxel versus Pemetrexed in Second-Line Chemotherapy for Stage IIIb or IV Non-Small Cell Lung Cancer in China

description: <i>Background:</i> To study the cost-efficacy of docetaxel and pemetrexed as single agents versus platinum-based combination agents in second-line treatment of stage IIIb or IV non-small cell lung cancer (NSCLC) patients by evaluating chemotherapeutic indexes and medical costs. <i>Methods:</i> Treatment responses were evaluated by progression-free survival (PFS), overall survival (OS), hematological and gastrointestinal toxicities. <i>Results:</i> Two hundred and seven stage IIIb or IV NSCLC patients were recruited to this clinical observation retrospective study. Thirty-four subjects were treated with docetaxel (group A), 98 with platinum-based doublet chemotherapy with docetaxel (group B), 42 with pemetrexed (group C), and 33 patients with platinum-based doublet combination therapy with pemetrexed (group D). The average PFS of groups A and B was 3.28 and 4.58 months, respectively (p = 0.042). The mean PFS of groups C and D was 3.1 and 4.98 months, respectively (p = 0.017). The mean OS of these groups was 12.88, 13.17, 12.40 and 13.04 months, respectively, without significant differences. The total medical costs in these four groups amounted to USD 5,533, 7,745, 8,569 and 15,291, respectively. <i>Conclusions:</i> Platinum-based doublet chemotherapy with docetaxel or pemetrexed could significantly increase PFS, however, without significant OS improvement in comparison with using them as single agents. The medical expenses associated with doublet therapy were much higher than those associated with single therapy with a significant portion of the medical expenses spent on treating hematological and gastrointestinal toxicity.
DOI: 10.6084/m9.figshare.5121427
title: Supplementary Material for: A Role for All-Trans-Retinoic Acid in the Early Steps of Lymphatic Vasculature Development

description: The molecular mechanisms that regulate the earliest steps of lymphatic vascular system development are unknown. To identify regulators of lymphatic competence and commitment, we used an in vitro vascular assay with mouse embryonic stem cell-derived embryoid bodies (EBs). We found that incubation with retinoic acid (RA) and, more potently, with RA in combination with cAMP, induced the expression of the lymphatic competence marker LYVE-1 in the vascular structures of the EBs. This effect was dependent on RA receptor (RAR)-α and protein kinase A signaling. RA-cAMP incubation also promoted the development of CD31+/LYVE-1+/Prox1+ cell clusters. In situ studies revealed that RAR-α is expressed by endothelial cells of the cardinal vein in ED 9.5–11.5 mouse embryos. Timed exposure of mouse and <i>Xenopus</i> embryos to excess of RA upregulated LYVE-1 and VEGFR-3 on embryonic veins and increased formation of Prox1-positive lymphatic progenitors. These findings indicate that RA signaling mediates the earliest steps of lymphatic vasculature development.
DOI: 10.6084/m9.figshare.5121430
title: Supplementary Material for: Molecular and Physiological Responses to Juvenile Traumatic Brain Injury: Focus on Growth and Metabolism

description: Traumatic brain injury (TBI), one of the most frequent causes of neurologic and neurobehavioral morbidity in the pediatric population, can result in lifelong challenges not only for patients, but also for their families. Survivors of a brain injury experienced during childhood – when the brain is undergoing a period of rapid development – frequently experience unique challenges as the consequences of their injuries are overlaid on normal developmental changes. Experimental studies have significantly advanced our understanding of the mechanisms and underlying molecular underpinnings of the injury response and recovery process following a TBI in the developing brain. In this paper, normal and TBI-related alterations in growth, development and metabolism are comprehensively reviewed in the postweanling/juvenile age range in the rat (postnatal days 21–60). As part of this review, TBI-related changes in gene expression are presented, with a focus on the injury-induced alterations related to cerebral growth and metabolism, and discussed in the context of existing literature related to physiological and behavioral responses to experimental TBI. Increasing evidence from the existing literature and from our own gene microarray data indicates that molecular responses related to growth, development and metabolism may play a particularly important role in the injury response and the recovery trajectory following developmental TBI. While gene expression analysis shows many of these changes occur at the level of transcription, a comprehensive review of other studies suggests that the control of metabolic substrates may preferentially be regulated through changes in transporters and enzymatic activity. The interrelation between cellular metabolism and activity-dependent neuroplasticity shows great promise as an area for future study for an optimal translation of experimental data to clinical TBI, with the ultimate goal of guiding therapeutic interventions.
DOI: 10.6084/m9.figshare.5121433
title: Supplementary Material for: Characterization and Genomic Organization of <i>PERI</i>, a Repetitive DNA in the <i>Drosophila buzzatii</i> Cluster Related to <i>DINE-1</i> Transposable Elements and Highly Abundant in the Sex Chromosomes

description: <i>Background/Aims: </i>Transposable elements (TEs) are dynamic components of eukaryotic genomes. We aimed to characterize TEs to help elucidate their impact on the genomic architecture, diversity and evolution of chromosomes in the <i>D. buzzatii</i> cluster of species (<i>repleta</i> group). <i>Methods: </i>A full TE element of <i>D. buzzatii</i>, named <i>PERI</i>, was identified in a BAC clone available in GenBank. <i>PERI</i> was further analysed using bioinformatics tools, PCR and in-situ hybridization to metaphase chromosomes and DNA fibers. <i>Results: </i><i>PERI</i> shares several structures in common with <i>DINE-1</i>, an abundant TE found widespread along the <i>Drosophila</i> genus. The central region of <i>PERI</i> is very dynamic but revealed a disrupted pattern of nucleotide variability among its internal tandem repeats. The minimal sequence variation in <i>D. serido</i> suggests recent amplification. <i>PERI</i> accumulates near or at heterochromatic regions of all 6 pairs of chromosomes, especially on the sex chromosomes, with some clustering. <i>Conclusions: </i><i>PERI</i> is an abundant type of <i>DINE-1</i> transposon but with characteristic sequence signatures and probably restricted to the <i>buzzatii </i>complex. The conservation of different central domains and association with genes suggests selective constraints. Although at or near heterochromatin, the distribution of <i>PERI</i> does not overlap with satDNAs, probably a consequence of functional or molecular constraints.
DOI: 10.6084/m9.figshare.5121436.v1
title: Supplementary Material for: Extensive Changes in the Expression of the Opioid Genes between Humans and Chimpanzees

description: The various means by which the body perceives, transmits, and resolves the experiences of pain and nociception are mediated by a host of molecules, including neuropeptides within the opioid gene signaling pathway. The peptide ligands and receptors encoded by this group of genes have been linked to behavioral disorders as well as a number of psychiatric affective disorders. Our aim was to explore the recent evolutionary history of these two gene families by taking a comparative genomics approach, specifically through a comparison between humans and chimpanzees. Our analyses indicate differential expression of these genes between the two species, more than expected based on genome-wide comparisons, indicating that differential expression is pervasive among the opioid genes. Of the 8 family members, three genes showed significant expression differences <i>(PENK</i>, <i>PNOC</i>, and <i>OPRL1)</i>, with two others marginally significant <i>(OPRM1</i> and <i>OPRD1)</i>. Accelerated substitution rates along human and chimpanzee lineages within the putative regulatory regions of <i>OPRM1</i>, <i>POMC</i>, and <i>PDYN</i> between the human and chimpanzee branches are consistent with positive selection. Collectively, these results suggest that there may have been a selective advantage to modulating the expression of the opioid genes in humans compared with our closest living relatives. Information about the cognitive roles mediated by these genes in humans may help to elucidate the trait consequences of these putatively adaptive expression changes.
DOI: 10.6084/m9.figshare.5121421
title: Supplementary Material for: Portrayal of the Notch System in Embryonic Stem Cell-Derived Embryoid Bodies

description: We portrayed the Notch system in embryonic stem cell (ESC)-derived embryoid bodies (EBs) differentiating under the standard protocols used to assess yolk sac (YS) hematopoiesis in vitro. Notch receptors and Notch ligands were detected in virtually all cells throughout EB development. Notch1 and Notch 2, but not Notch4, were visualized in the nucleus of EB cells, and all these receptors were also observed as patent cytoplasmic foci. Notch ligands (Delta-like1 and 4, Jagged1 and 2) were immunodetected mostly as cytoplasmic foci. Widespread Notch1 activation was evident at days 2–4 of EB differentiation, the time window of hemangioblast generation in this in vitro system. EBs experienced major spatial remodeling beyond culture day 4, the time point coincident with the transition between primitive and multilineage waves of YS hematopoiesis in vitro. At day 6, where definitive YS hematopoiesis is established in EBs, these exhibit an immature densely packed cellular region (DCR) surrounded by a territory of mesodermal-like cells and an outer layer of endodermal cells. Immunolabeling of Notch receptors and ligands was usually higher in the DCR. Our results show that Notch system components are continuously and abundantly expressed in the multicellular environments arising in differentiating EBs. In such an active Notch system, receptors and ligands do not accumulate extensively at the cell surface but instead localize at cytoplasmic foci, an observation that fits current knowledge on endocytic modulation of Notch signaling. Our data thus suggest that Notch may function as a territorial modulator during early development, where it may eventually influence YS hematopoiesis.
DOI: 10.6084/m9.figshare.5121424
title: Supplementary Material for: EIF2C Is Overexpressed and Amplified in Head and Neck Squamous Cell Carcinoma

description: <i>Aim:</i> To discover putative oncogenes in head and neck squamous cell carcinoma (HNSCC) by integrating data from whole-genome comparison of array-based comparative genomic hybridization (CGH) and expression microarray analysis of HNSCC. <i>Methods:</i> We integrated published data defining regions of loss/gain identified from the profiling of 21 HNSCC using high-resolution (&lt;1 Mb) CGH arrays and data from an mRNA expression microarray (approx. 12,000 genes) comparing 6 normal tissues and 8 HNSCC tumor tissues. Eukaryotic translation initiation factor 2C subunit 2<i> (EIF2C2)</i> was found to be the most significantly overexpressed gene by mRNA expression array, and corresponded to the most common region of amplification found by the CGH array described by Sparano et al. We validated <i>EIF2C2</i> overexpression in primary tissue, overexpression and amplification in HNSCC lines (JHU-011, JHU-012, FADU) relative to a minimally transformed oral keratinocyte cell line (OKF6) and performed knockdown experiments. <i>Results:</i> The tumor tissues had an average mRNA expression level of 123 (SD = 49) compared to the normal tissues (18.6, SD = 10) (p = 0.0005) by expression array. Quantitative RT-PCR validation of our expression arrays found that normal tissues had an average expression of 0.76 (SE = 0.08) and tumor tissues of 2.1 (SE = 0.35) (p = 0.0008). <i>EIF2C2</i> was found to be amplified and overexpressed in 3 HNSCC cell lines. Knockdown of <i>EIF2C2</i> in cell lines (JHU-012 and JHU-011) inhibited proliferation. <i>Conclusion:</i><i>EIF2C2</i> is amplified and overexpressed in HNSCC cell lines and primary tumors and functionally significant in cell lines.