cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5123755
title: Supplementary Material for: Neuropeptide TLQP-21, a VGF Internal Fragment, Modulates Hormonal Gene Expression and Secretion in GH3 Cell Line

description: In the present study we demonstrated that TLQP-21, a biologically active peptide derived from the processing of the larger pro-VGF granin, plays a role in mammotrophic cell differentiation. We used an established in vitro model, the GH3 cell line, which upon treatment with epidermal growth factor develops a mammotrophic phenotype consisting of induction of prolactin expression and secretion, and inhibition of growth hormone. Here we determined for the first time that during mammotrophic differentiation, epidermal growth factor also induces Vgf gene expression and increases VGF protein precursor processing and peptide secretion. After this initial observation we set out to determine the specific role of the VGF encoded TLQP-21 peptide on this model. TLQP-21 induced a trophic effect on GH3 cells and increased prolactin expression and its own gene transcription without affecting growth hormone expression. TLQP-21 was also able to induce a significant rise of cytoplasmic calcium, as measured by Fura2AM, due to the release from a thapsigargin-sensitive store. TLQP-21-dependent rise in cytoplasmic calcium was, at least in part, dependent on the activation of phospholipase followed by phosphorylation of PKC and ERK. Taken together, the present results demonstrate that TLQP-21 contributes to differentiation of the GH3 cell line toward a mammotrophic phenotype and suggest that it may exert a neuroendocrine role in vivo on lactotroph cells in the pituitary gland.
DOI: 10.6084/m9.figshare.5123764.v1
title: Supplementary Material for: Chromosome Evolution in Eulipotyphla

description: We integrated chromosome painting information on 5 core-insectivora species available in the literature with new Zoo-FISH data for Iberian shrew <i>(Sorex granarius)</i> and Altai mole <i>(Talpa altaica)</i>. Our analysis of these 7 species allowed us to determine the chromosomal features of Eulipotyphla genomes and to update the previously proposed ancestral karyotype for 2 main groups of the <i>Sorex </i>genus. The chromosome painting evidence with human painting probes (HSA) reveals the presence of the 2 unique associations HSA4/5 and 1/10p/12/22b, which support Eulipotyphla. There are a series of synapomorphies both for Erinaceidae (HSA3/1/5, 3/17, 11/15 and 10/20) and for Soricinae (HSA5/9, 6/7/16, 8/3/21 and 11/12/22). We found associations that link Talpidae/Erinaceidae (HSA7/8, 1/5 and 1/19p), Talpidae/Soricidae (HSA1/8/4) and Erinaceidae/Soricidae (HSA4/20 and 2/13). Genome conservation in Eulipotyphla was estimated on the basis of the number of evolutionary breaks in the ancestral mammalian chromosomes. In total, 7 chromosomes of the boreo-eutherian ancestor (BEA8 or 10, 9, 17, 18, 20–22) were retained in all eulipotyphlans studied; among them moles show the highest level of chromosome conservation. The integration of sequence data into the chromosome painting information allowed us to further examine the chromosomal syntenies within a phylogenetic perspective. Based on our analysis we offer the most parsimonious reconstruction of phylogenetic relationships in Eulipotyphla. The cytogenetic reconstructions based on these data do not conflict with molecular phylogenies supporting basal position of Talpidae in the order.
DOI: 10.6084/m9.figshare.5123743
title: Supplementary Material for: Differential Regulation by Toll-Like Receptor Agonists Reveals That<b><i> MCPIP1</i></b> Is the Potent Regulator of Innate Immunity in Bacterial and Viral Infections

description: Toll-like receptors (TLRs) are key molecules in innate immunity that recognize a variety of pathogen-associated molecular patterns. Activation of TLRs by their agonists initiates several signaling cascades, which eventually result in the expression of immune modifiers. Despite the fact that MCPIP1 is reported as an important immune regulator involved in macrophage activation, modulation of its expression by all known TLR agonists has never been documented. In this study, we present for the first time that in human monocyte-derived macrophages all TLR agonists, except CpG, markedly induced the expression of MCPIP1. The level of the induced transcript, as well as the protein and time of their appearance varied depending on the agonist. Furthermore, we confirmed the strong and differential upregulation of <i>MCPIP1</i> during bacteria, virus and fungus infection. <i>MCPIP1 </i>belongs to a group of early-response genes; however, in the present study, we show for the first time the sustained high level of <i>MCPIP1 </i>expression during long-term <i>Staphylococcus aureus</i> infection. Taken together, our results implicate <i>MCPIP1</i> as a potent regulator of innate immunity, which can be strongly engaged in the pathogenesis of acute and chronic infective diseases.
DOI: 10.6084/m9.figshare.5123752
title: Supplementary Material for: Effective Improvement of <i>D</i>-Phenylglycine Aminotransferase Solubility by Protein Crystal Contact Engineering

description: Structure-guided genetic engineering of <i>D</i>-phenylglycine aminotransferase (<i>D</i>-PhgAT) aimed at increasing protein solubility was attempted. In silico analyses predicted the Asn439 and Gln444 as highly solvent-exposed β-turn residues involved with protein crystal contact (CC) potential candidates for solubility-improving mutations. They were replaced with Asp and Glu creating the N439D and Q444E single mutants, and N439D/Q444E double mutant with 2.5-, 3.3- and 5.9-fold increases in solubility, respectively. The protein CC prevention effect rather than the net charge effect accounted for the dramatically improved solubility since the N439D, Q444E and N439D/Q444E mutations altered the isoelectric point of <i>D</i>-PhgAT by only 0.1, 0.1 and 0.3 units, respectively. Examination of the <i>D</i>-PhgAT structural model revealed that the N439D mutation weakened the CC attraction force and the Q444E mutation created electrostatic repulsion at the CC point. Analysis of circular dichroism spectra, melting temperature, and <i>D</i>-PhgAT-specific activity showed that the mutations posed no unfavorable effect on the conformational stability and catalytic performance of the enzyme. The protein solubility-improving strategy employed on <i>D</i>-PhgAT in this study was successful with minimal protein structure modification required. It should be applicable with a high chance of success for other proteins, especially those with 3-D structural models available.
DOI: 10.6084/m9.figshare.5123758.v1
title: Supplementary Material for: Characterization of New Organic Nitrate Hybrid Drugs Covalently Bound to Valsartan and Cilostazol

description: <b><i>Background and Purpose:</i></b> Organic nitrates represent a group of nitrovasodilators that are clinically used for the treatment of ischemic heart disease. With the present studies we synthesized and characterized new organic nitrate hybrid molecules. Compounds CLC-1265 (valsartan mononitrate) and CLC-1280 (valsartan dinitrate) are derivatives of the angiotensin receptor blocker valsartan, with CLC-1265 containing a single organic nitrate linker and CLC-1280 also containing a second, different linker. Compounds CLC-2000 (cilostazol mononitrate) and CLC-2100 (cilostazol dinitrate) are nitrate derivatives of the phosphodiesterase III inhibitor cilostazol. All compounds are designed as hybrid molecules, potentially combining the NO-donating properties of organic nitrates with the AT1-blocking activity of valsartan or the phosphodiesterase-III–inhibiting effect of cilostazol. <b><i>Experimental Approach:</i></b> The properties of new drugs were assessed by isometric tension recording, inhibition of platelet aggregation and formation of mitochondrial reactive oxygen and nitrogen species. <b><i>Key Results:</i></b> In this report, all new nitrate compounds are shown, in vitro, to induce vasodilation in the range of other, classical organic nitrates, without inducing oxidative stress or classical nitrate tolerance. In addition, the new hybrid nitrate molecules displayed superior antiaggregatory properties over classical mono- and dinitrates. <b><i>Conclusions and Implications:</i></b> Our results demonstrate that organic nitrates can be successfully linked to existing therapeutic molecules to create a new class of molecular entities with a potential dual mechanism of action via combining the established pharmacological properties of valsartan or cilostazol with the vasodilating properties of organic nitrates. Future experimental studies have to demonstrate whether the combined action of these compounds translates to superior therapeutic effects.
DOI: 10.6084/m9.figshare.5123743.v1
title: Supplementary Material for: Differential Regulation by Toll-Like Receptor Agonists Reveals That<b><i> MCPIP1</i></b> Is the Potent Regulator of Innate Immunity in Bacterial and Viral Infections

description: Toll-like receptors (TLRs) are key molecules in innate immunity that recognize a variety of pathogen-associated molecular patterns. Activation of TLRs by their agonists initiates several signaling cascades, which eventually result in the expression of immune modifiers. Despite the fact that MCPIP1 is reported as an important immune regulator involved in macrophage activation, modulation of its expression by all known TLR agonists has never been documented. In this study, we present for the first time that in human monocyte-derived macrophages all TLR agonists, except CpG, markedly induced the expression of MCPIP1. The level of the induced transcript, as well as the protein and time of their appearance varied depending on the agonist. Furthermore, we confirmed the strong and differential upregulation of <i>MCPIP1</i> during bacteria, virus and fungus infection. <i>MCPIP1 </i>belongs to a group of early-response genes; however, in the present study, we show for the first time the sustained high level of <i>MCPIP1 </i>expression during long-term <i>Staphylococcus aureus</i> infection. Taken together, our results implicate <i>MCPIP1</i> as a potent regulator of innate immunity, which can be strongly engaged in the pathogenesis of acute and chronic infective diseases.
DOI: 10.6084/m9.figshare.5123746
title: Supplementary Material for: Morphometric Analysis of Telencephalic Structure in a Variety of Neognath and Paleognath Bird Species Reveals Regional Differences Associated with Specific Behavioral Traits

description: Birds exhibit a huge array of behavior, ecology and physiology, and occupy nearly every environment on earth, ranging from the desert outback of Australia to the tropical rain forests of Panama. Some birds have adopted a fully nocturnal lifestyle, such as the barn owl and kiwi, while others, such as the albatross, spend nearly their entire life flying over the ocean. Each species has evolved unique adaptations over millions of years to function in their respective niche. In order to increase processing power or network efficiency, many of these adaptations require enlargements and/or specializations of the brain as a whole or of specific brain regions. In this study, we examine the relative size and morphology of 9 telencephalic regions in a number of Paleognath and Neognath birds and relate the findings to differences in behavior and sensory ecology. We pay particular attention to those species that have undergone a relative enlargement of the telencephalon to determine whether this relative increase in telencephalic size is homogeneous across different brain regions or whether particular regions have become differentially enlarged. The analysis indicates that changes in the relative size of telencephalic regions are not homogeneous, with every species showing hypertrophy or hypotrophy of at least one of them. The three-dimensional structure of these regions in different species was also variable, in particular that of the mesopallium in kiwi. The findings from this study provide further evidence that the changes in relative brain size in birds reflect a process of mosaic evolution.
DOI: 10.6084/m9.figshare.5123749
title: Supplementary Material for: Identification of Two DNA Helicases UvrD and DinG as Suppressors for Lethality Caused by Mutant cspA mRNAs

description: CspA is a major cold shock-inducible protein (70 aa), and its major role in the cold shock response was shown to be as an RNA chaperone destabilizing secondary structure of mRNAs at low temperature. Previously, we showed that the overexpression of mutant <i>cspA</i> containing premature non-sense codons at various positions led to stalled ribosomes on mutant <i>cspA</i> transcripts, ultimately leading to cell death. This lethality is primarily due to the highly translatable <i>cspA</i> 5′-<i>UTR</i> that recruits most of the ribosomes from other mRNAs, which are then stalled at the abnormal stop codon. This was called the ‘LACE’ effect. We show here that non-sense mutation even at the 67th position as well as substitutions of aromatic amino acid residues present on the RNA-binding surface of CspA protein to alanine caused the LACE effect by trapping a substantial amount of ribosomes on <i>cspA</i> mRNAs. In an attempt to identify a suppressor(s), which may help the cells to recover from the inhibitory LACE effect, genetic screening of an <i>Escherichia coli</i> genomic library was performed. We isolated suppressors that contained the genomic fragments encoding <i>uvrD</i> and <i>dinG</i>, respectively, whose gene products are ATP-dependent DNA helicases. The nucleic acid-binding and ATPase activities of these two helicases were found to be essential for their suppression activity. This genomic screening offers an approach to shed light on the mechanistic of 5′-<i>UTR</i> of <i>cspA</i> mRNA and novel roles of <i>E. coli</i> helicases that function in DNA repair.
DOI: 10.6084/m9.figshare.5123740
title: Supplementary Material for: Natural History of Postoperative Nonfunctioning Pituitary Adenomas: A Systematic Review and Meta-Analysis

description: <b><i>Objective:</i></b> Previous studies attempting to define the natural history of postoperative nonfunctioning pituitary adenomas (pNFPAs) were somewhat limited by selection bias and/or small numbers and/or lack of consistency among the study findings. The aim of this study was to scrutinize the literature in order to analyze the natural history of pNFPAs. <b><i>Methods:</i></b> Electronic database including MEDLINE, PubMed and Cochrane CENTRAL were searched. The literature relating to the patients with pNFPAs without postoperative radiotherapy and pharmacotherapy was collected. Eligible studies reported on the rate of tumor recurrence, the tumor growth-free survival rate (TGFSR) at 5 and 10 years, and/or the residual tumor volume doubling time (TVDT). <b><i>Results:</i></b> 19 studies met the criteria. The pNFPAs were divided into two groups: the pooled recurrence rate of group I without detectable residual tumor (371 patients) was 12% (95% CI 6–19%), the TGFSR at 5 and 10 years were 96% (95% CI 89–99%) and 82% (95% CI 65–94%), respectively. The pooled recurrence rate of group II with residual tumor (600 patients) was 46% (95% CI 36–56%), the TGFSR at 5 and 10 years were 56% (95% CI 41–71%) and 40% (95% CI 27–53%), respectively. The mean TVDT was 3.4 years (95% CI 2.4–4.5 years). <b><i>Conclusions:</i></b> pNFPAs, with or without detectable residual tumor, need stratification of treatment and radiological/endocrinological follow-up strategy. According to the TVDT, residual tumor regrowth is very slow, which permits an extensive and safe follow-up program for most patients.
DOI: 10.6084/m9.figshare.5123746.v1
title: Supplementary Material for: Morphometric Analysis of Telencephalic Structure in a Variety of Neognath and Paleognath Bird Species Reveals Regional Differences Associated with Specific Behavioral Traits

description: Birds exhibit a huge array of behavior, ecology and physiology, and occupy nearly every environment on earth, ranging from the desert outback of Australia to the tropical rain forests of Panama. Some birds have adopted a fully nocturnal lifestyle, such as the barn owl and kiwi, while others, such as the albatross, spend nearly their entire life flying over the ocean. Each species has evolved unique adaptations over millions of years to function in their respective niche. In order to increase processing power or network efficiency, many of these adaptations require enlargements and/or specializations of the brain as a whole or of specific brain regions. In this study, we examine the relative size and morphology of 9 telencephalic regions in a number of Paleognath and Neognath birds and relate the findings to differences in behavior and sensory ecology. We pay particular attention to those species that have undergone a relative enlargement of the telencephalon to determine whether this relative increase in telencephalic size is homogeneous across different brain regions or whether particular regions have become differentially enlarged. The analysis indicates that changes in the relative size of telencephalic regions are not homogeneous, with every species showing hypertrophy or hypotrophy of at least one of them. The three-dimensional structure of these regions in different species was also variable, in particular that of the mesopallium in kiwi. The findings from this study provide further evidence that the changes in relative brain size in birds reflect a process of mosaic evolution.
DOI: 10.6084/m9.figshare.5123731
title: Supplementary Material for: Less Cognitive and Neurological Deficits in Schizophrenia Patients Carrying Risk Variant in <b><i>ZNF804A</i></b>

description: <b><i>Background:</i></b> The rs1344706 single nucleotide polymorphism in the <i>ZNF804A</i> gene is a common variant with strong evidence for association with schizophrenia. Recent studies show an association of rs1344706 with cognitive functioning, and there is some evidence suggesting that the risk allele may increase susceptibility for a subtype of schizophrenia with relatively spared cognition. <b><i>Methods:</i></b> We tested the effect of rs1344706 genotype in 89 schizophrenia patients on 3 basic cognitive domains (working memory, processing speed and attention) shown to be severely impaired in schizophrenia. Also we investigated the effect of rs1344706 on the severity of neurological soft signs, subtle impairments in motor and sensory functions highly frequent in schizophrenia patients. Neurological soft signs and cognitive deficits are central features of schizophrenia and are tightly linked with clinical, social and functional outcome. <b><i>Results:</i></b> Our results show an association of higher rs1344706 risk allele load with improved performance on processing speed and with fewer neurological soft signs. <b><i>Conclusions:</i></b> Together with other studies, our findings suggest that <i>ZNF804A</i> is associated with a subtype of schizophrenia with better cognitive and neurological functioning. Discovery of the specific pathways through which <i>ZNF804A</i> is exerting this effect may lead to better prevention, diagnosis and treatment for a specific group of schizophrenia patients.
DOI: 10.6084/m9.figshare.5123728
title: Supplementary Material for: Comparative Study on the Difference in Functional Outcomes at Discharge between Proximal and Total Gastrectomy

description: Several studies have regarded proximal gastrectomy (PG) as optimal compared to total gastrectomy (TG) for upper stomach cancer. In addition to the traditional outcomes of complication and mortality, change in functional status should be considered as another relevant outcome in aging generations. However, there has been no community-based appraisal of functional outcomes between PG and TG. Using an administrative database, we compared functional outcomes between PG and TG. Among 12,508 patients who survived for ≥15 years and underwent open gastrectomy between 2008 and 2010, we examined patient characteristics, comorbidities, functional status estimated by the Barthel index (BI) at admission and discharge, complications, ICU care, ventilation administration, blood transfusion, operating room time, resumption of oral intake, length of stay and total charges. With reference to distal gastrectomy (DG), we performed multivariate analyses to assess the impacts of PG and TG on complications and BI deterioration. A total of 434 PGs and 4,941 TGs were observed in 148 and 295 hospitals, respectively. Patient characteristics, care process, resumption of oral intake, operating room time, length of stay and total charges were also significantly different among the three gastrectomy types. PG, TG and DG were not associated with complications or functional deterioration. Patient characteristics, preoperative blood transfusion and longer operating room time were significantly associated with more complications and BI deterioration. Since patient case mix and longer operating room time were associated with poor outcomes, physicians should recognize the role of PG and might optimally challenge and complete gastrectomies within the appropriate indications.
DOI: 10.6084/m9.figshare.5123734
title: Supplementary Material for: Novel Uromodulin Mutation in Familial Juvenile Hyperuricemic Nephropathy

description: <b><i>Background:</i></b> Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant disorder characterized by early onset of hyperuricemia, decreased fractional renal urate excretion and progressive interstitial nephropathy. Mutations in the uromodulin<i> (UMOD)</i> gene encoding uromodulin/Tamm-Horsfall, a glycosylphosphatidylinositol (GPI)-anchored protein, cause this disease. <b><i>Methods:</i></b> One Chinese family with 13 FJHN-affected individuals is described. Clinical data, blood and urine samples of 7 affected members (all alive patients in this family) and 15 unaffected members were collected. Mutation analysis of the <i>UMOD</i> gene was performed by polymerase chain reaction and direct sequencing. Urinary uromodulin from affected or unaffected members of this family and healthy controls was examined by enzyme-linked immunosorbent assay kit. Expression of uromodulin in renal tissue was shown with immunofluorescence. <b><i>Results:</i></b> A novel mutation (p.T605G) within the uromodulin GPI anchor signal segment was identified in the affected individuals of this FJHN family. There was a markedly increased expression of uromodulin in renal tissue and significantly decreased urinary excretion of uromodulin in affected patients with an estimated glomerular filtration rate &lt;60 ml/min/1.73 m<sup>2</sup>. <b><i>Conclusions:</i></b> The present study reported a novel mutation in exon 9 of <i>UMOD</i> in the Chinese Han population, within the GPI anchor signal segment of uromodulin. Since the GPI anchor is linked with the release or secretion of proteins, our finding may provide further evidence for the underlying mechanism of decreased urinary excretion of uromodulin in FJHN.