cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.6591551
title: ROS is the major player in regulating altered autophagy and lifespan in <i>sin-3</i> mutants of <i>C. elegans</i>

description: SIN3, a transcriptional corepressor has been implicated in varied functions both as transcription activator and repressor. Recent studies associated Sin3 with the macroautophagic/autophagic process as a negative regulator of Atg8 and Atg32. Though the role of SIN3 in autophagy is being explored, little is known about the overall effect of <i>SIN3</i> deletion on the survival of an organism. In this study using a <i>Caenorhabditis elegans sin-3(tm1279);him-5(e1490)</i> strain, we demonstrate that under <i>in vivo</i> conditions SIN-3 differentially modulates autophagy and lifespan. We provide evidence that the enhanced autophagy and decreased lifespan observed in <i>sin-3</i> deletion mutants is dependent on ROS and intracellular oxidative stress. Inability of the mutant worms to maintain redox balance along with dysregulation of enzymatic antioxidants, depletion of GSH and NADP reserves and elevation of ROS markers compromises the longevity of the worms. It is possible that the enhanced autophagic process observed in <i>sin-3(tm1279);him-5(e1490)</i> worms is required to compensate for oxidative stress generated in these worms. <b>Abbreviations:</b><i>cat</i>: catalase; DCFDA: 2ʹ,7ʹ-dichlorodihydrofluoroscein diacetate; GSH: reduced glutathione; GSSG: oxidized glutathione; H<sub>2</sub>O<sub>2</sub>: hydrogen peroxide; HDAC: Histone deacetylase; HID: HDAC interacting domain; <i>him-5</i>: high incidence of males; HLH-30: Helix Loop Helix-30; HNE: 4-hydroxyl-2-noneal; LIPL: LIPase Like; MDA: malondialdehyde; NGM: nematode growth medium; PAH: paired amphipathic α-helix; PE: phosphatidylethanolamine; RFU: relative fluorescence unit; ROS: reactive oxygen species; <i>sin-3/SIN3</i>: yeast Switch Independent; SOD: superoxide dismutase; NADP: nicotinamide adenine dinucleotide phosphate; SQST-1: SeQueSTosome related-1; ATG: AuTophaGy related
DOI: 10.6084/m9.figshare.6591551.v1
title: ROS is the major player in regulating altered autophagy and lifespan in <i>sin-3</i> mutants of <i>C. elegans</i>

description: SIN3, a transcriptional corepressor has been implicated in varied functions both as transcription activator and repressor. Recent studies associated Sin3 with the macroautophagic/autophagic process as a negative regulator of Atg8 and Atg32. Though the role of SIN3 in autophagy is being explored, little is known about the overall effect of <i>SIN3</i> deletion on the survival of an organism. In this study using a <i>Caenorhabditis elegans sin-3(tm1279);him-5(e1490)</i> strain, we demonstrate that under <i>in vivo</i> conditions SIN-3 differentially modulates autophagy and lifespan. We provide evidence that the enhanced autophagy and decreased lifespan observed in <i>sin-3</i> deletion mutants is dependent on ROS and intracellular oxidative stress. Inability of the mutant worms to maintain redox balance along with dysregulation of enzymatic antioxidants, depletion of GSH and NADP reserves and elevation of ROS markers compromises the longevity of the worms. It is possible that the enhanced autophagic process observed in <i>sin-3(tm1279);him-5(e1490)</i> worms is required to compensate for oxidative stress generated in these worms. <b>Abbreviations:</b><i>cat</i>: catalase; DCFDA: 2ʹ,7ʹ-dichlorodihydrofluoroscein diacetate; GSH: reduced glutathione; GSSG: oxidized glutathione; H<sub>2</sub>O<sub>2</sub>: hydrogen peroxide; HDAC: Histone deacetylase; HID: HDAC interacting domain; <i>him-5</i>: high incidence of males; HLH-30: Helix Loop Helix-30; HNE: 4-hydroxyl-2-noneal; LIPL: LIPase Like; MDA: malondialdehyde; NGM: nematode growth medium; PAH: paired amphipathic α-helix; PE: phosphatidylethanolamine; RFU: relative fluorescence unit; ROS: reactive oxygen species; <i>sin-3/SIN3</i>: yeast Switch Independent; SOD: superoxide dismutase; NADP: nicotinamide adenine dinucleotide phosphate; SQST-1: SeQueSTosome related-1; ATG: AuTophaGy related
DOI: 10.6084/m9.figshare.6591548
title: Cryptic exon splicing function of TARDBP interacts with autophagy in nervous tissue

description: TARDBP (TAR DNA binding protein) is one of the components of neuronal aggregates in sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. We have developed a simple quantitative method to evaluate TARDBP splicing function that was applied to spinal cord, brainstem, motor cortex, and occipital cortex in ALS (n = 8) cases compared to age- and gender-matched control (n = 17). Then, we quantified the abundance of a TARDBP-spliced cryptic exon present in <i>ATG4B</i> (autophagy related 4B cysteine peptidase) mRNA. Results of these analyses demonstrated that the loss of this <i>TARDBP</i> function in spinal cord, brainstem, motor cortex, and occipital cortex differentiated ALS from controls (area under the curve of receiver operating characteristic: 0.85). Significant correlations were also observed between cryptic exon levels, age, disease duration, and aberrant mRNA levels. To test if <i>TARDBP</i> function in splicing is relevant in <i>ATG4B</i> major function (autophagy) we downregulated <i>TARDBP</i> expression in human neural tissue and in HeLa cells, demonstrating that TARDBP is required for maintaining the expression of <i>ATG4B</i>. Further, <i>ATG4B</i> overexpression alone is sufficient to completely prevent the increase of SQSTM1 induced by <i>TARDBP</i> downregulation in human neural tissue cells and in cell lines. In conclusion, the present findings demonstrate abnormal alternative splicing of <i>ATG4B</i> transcripts in ALS neural tissue in agreement with <i>TARDBP</i> loss of function, leading to impaired autophagy. <b>Abbreviations</b>: ALS: amyotrophic lateral sclerosis; <i>ATG4B</i>: autophagy related 4B cysteine peptidase; AUC: area under the curve; FTLD: frontotemporal lobar degeneration; iPSC: induced pluripotent stem cells; ROC: receiver operating characteristic; <i>TARDBP</i>: TAR DNA binding protein; RT-qPCR: quantitative RT-PCR
DOI: 10.6084/m9.figshare.6591548.v2
title: Cryptic exon splicing function of TARDBP interacts with autophagy in nervous tissue

description: TARDBP (TAR DNA binding protein) is one of the components of neuronal aggregates in sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. We have developed a simple quantitative method to evaluate TARDBP splicing function that was applied to spinal cord, brainstem, motor cortex, and occipital cortex in ALS (n = 8) cases compared to age- and gender-matched control (n = 17). Then, we quantified the abundance of a TARDBP-spliced cryptic exon present in <i>ATG4B</i> (autophagy related 4B cysteine peptidase) mRNA. Results of these analyses demonstrated that the loss of this <i>TARDBP</i> function in spinal cord, brainstem, motor cortex, and occipital cortex differentiated ALS from controls (area under the curve of receiver operating characteristic: 0.85). Significant correlations were also observed between cryptic exon levels, age, disease duration, and aberrant mRNA levels. To test if <i>TARDBP</i> function in splicing is relevant in <i>ATG4B</i> major function (autophagy) we downregulated <i>TARDBP</i> expression in human neural tissue and in HeLa cells, demonstrating that TARDBP is required for maintaining the expression of <i>ATG4B</i>. Further, <i>ATG4B</i> overexpression alone is sufficient to completely prevent the increase of SQSTM1 induced by <i>TARDBP</i> downregulation in human neural tissue cells and in cell lines. In conclusion, the present findings demonstrate abnormal alternative splicing of <i>ATG4B</i> transcripts in ALS neural tissue in agreement with <i>TARDBP</i> loss of function, leading to impaired autophagy. <b>Abbreviations</b>: ALS: amyotrophic lateral sclerosis; <i>ATG4B</i>: autophagy related 4B cysteine peptidase; AUC: area under the curve; FTLD: frontotemporal lobar degeneration; iPSC: induced pluripotent stem cells; ROC: receiver operating characteristic; <i>TARDBP</i>: TAR DNA binding protein; RT-qPCR: quantitative RT-PCR
DOI: 10.6084/m9.figshare.6591548.v1
title: CRYPTIC EXON SPLICING FUNCTION OF TARDBP INTERACTS WITH AUTOPHAGY IN NERVOUS TISSUE

description: TARDBP (TAR DNA binding protein) is one of the components of neuronal aggregates in sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. We have developed a simple quantitative method to evaluate TARDBP splicing function that was applied to spinal cord, brainstem, motor cortex, and occipital cortex in ALS (n=8) cases compared to age- and gender-matched control (n=17). Then, we quantified the abundance of a TARDBP-spliced cryptic exon present in <i>ATG4B</i> (autophagy related 4B cysteine peptidase) mRNA. Results of these analyses demonstrated that the loss of this <i>TARDBP</i> function in spinal cord, brainstem, motor cortex, and occipital cortex differentiated ALS from controls (area under the curve of receiver operating characteristic: 0.85). Significant correlations were also observed between cryptic exon levels, age, disease duration, and aberrant mRNA levels. To test if <i>TARDBP</i> function in splicing is relevant in <i>ATG4B</i> major function (autophagy) we downregulated <i>TARDBP</i> expression in human neural tissue and in HeLa cells, demonstrating that TARDBP is required for maintaining the expression of <i>ATG4B</i>. Further, <i>ATG4B</i> overexpression alone is sufficient to completely prevent the increase of SQSTM1 induced by <i>TARDBP</i> downregulation in human neural tissue cells and in cell lines. In conclusion, the present findings demonstrate abnormal alternative splicing of <i>ATG4B</i> transcripts in ALS neural tissue in agreement with <i>TARDBP</i> loss of function, leading to impaired autophagy.
DOI: 10.6084/m9.figshare.6591515
title: New caviomorph rodents from the late Oligocene of Salla, Bolivia: taxonomic, chronological, and biogeographic implications for the Deseadan faunas of South America

description: Caviomorph rodents have been an important component of South American mammal faunas at least since the Oligocene. Those from the Deseadan South American Land Mammal Age (SALMA; late Oligocene) have been exhaustively studied because they are considered key to understanding the evolution of South American rodents. Deseadan faunas are widely distributed from northern Peru to central Patagonia, with those from Salla (Bolivia) and Cabeza Blanca (Argentinean Patagonia) being the most diverse. Recent studies of Deseadan rodents at some localities in high (Cabeza Blanca, Punta Nava, Scarritt Pocket) and low (Contamana) latitudes revealed greater taxonomic diversity. However, at middle latitudes, Salla has not received the same attention, despite being exceptional in terms of the abundance and high-quality preservation of specimens. The aim of this work is to report new caviomorph rodents from Salla, and to discuss their systematic and palaeobiogeographical implications in the context of the South American Deseadan caviomorph assemblages. We describe two new genera (†<i>Lapazomys</i> gen. nov. and †<i>Cholamys</i> gen. nov.) and five new species (†<i>Migraveramus lavocati</i> sp. nov., †<i>Sallamys woodi</i> sp. nov., †<i>Lapazomys hartenbergeri</i> sp. nov., †<i>Protosteiromys pattersoni</i> sp. nov. and †<i>Cholamys tetralophodonta</i> sp. nov.). These include the first erethizontids and the oldest Cavioidea <i>sensu stricto</i> for middle and low latitudes. The increase in the number of species corroborates the existence of an important rodent diversification already evidenced in the late early/early late Oligocene. In addition, the new rodents lessen the degree of endemism of the Salla rodent fauna proposed in previous papers. We interpret that the differences among Deseadan assemblages from low, middle and high latitudes are due essentially to climatic, historical and local environmental conditions, whereas diachronism seems less important in the modelling of faunas. http://zoobank.org/urn:lsid:zoobank.org:pub:A8A04332-12E1-4966-9807-47B66554718E
DOI: 10.6084/m9.figshare.6591515.v2
title: New caviomorph rodents from the late Oligocene of Salla, Bolivia: taxonomic, chronological, and biogeographic implications for the Deseadan faunas of South America

description: Caviomorph rodents have been an important component of South American mammal faunas at least since the Oligocene. Those from the Deseadan South American Land Mammal Age (SALMA; late Oligocene) have been exhaustively studied because they are considered key to understanding the evolution of South American rodents. Deseadan faunas are widely distributed from northern Peru to central Patagonia, with those from Salla (Bolivia) and Cabeza Blanca (Argentinean Patagonia) being the most diverse. Recent studies of Deseadan rodents at some localities in high (Cabeza Blanca, Punta Nava, Scarritt Pocket) and low (Contamana) latitudes revealed greater taxonomic diversity. However, at middle latitudes, Salla has not received the same attention, despite being exceptional in terms of the abundance and high-quality preservation of specimens. The aim of this work is to report new caviomorph rodents from Salla, and to discuss their systematic and palaeobiogeographical implications in the context of the South American Deseadan caviomorph assemblages. We describe two new genera (†<i>Lapazomys</i> gen. nov. and †<i>Cholamys</i> gen. nov.) and five new species (†<i>Migraveramus lavocati</i> sp. nov., †<i>Sallamys woodi</i> sp. nov., †<i>Lapazomys hartenbergeri</i> sp. nov., †<i>Protosteiromys pattersoni</i> sp. nov. and †<i>Cholamys tetralophodonta</i> sp. nov.). These include the first erethizontids and the oldest Cavioidea <i>sensu stricto</i> for middle and low latitudes. The increase in the number of species corroborates the existence of an important rodent diversification already evidenced in the late early/early late Oligocene. In addition, the new rodents lessen the degree of endemism of the Salla rodent fauna proposed in previous papers. We interpret that the differences among Deseadan assemblages from low, middle and high latitudes are due essentially to climatic, historical and local environmental conditions, whereas diachronism seems less important in the modelling of faunas. http://zoobank.org/urn:lsid:zoobank.org:pub:A8A04332-12E1-4966-9807-47B66554718E
DOI: 10.6084/m9.figshare.6591515.v1
title: New caviomorph rodents from the late Oligocene of Salla, Bolivia: taxonomic, chronological, and biogeographic implications for the Deseadan faunas of South America

description: Caviomorph rodents have been an important component of South American mammal faunas at least since the Oligocene. Those from the Deseadan South American Land Mammal Age (SALMA; late Oligocene) have been exhaustively studied because they are considered key to understanding the evolution of South American rodents. Deseadan faunas are widely distributed from northern Peru to central Patagonia, with those from Salla (Bolivia) and Cabeza Blanca (Argentinean Patagonia) being the most diverse. Recent studies of Deseadan rodents at some localities in high (Cabeza Blanca, Punta Nava, Scarritt Pocket) and low (Contamana) latitudes revealed greater taxonomic diversity. However, at middle latitudes, Salla has not received the same attention, despite being exceptional in terms of the abundance and high-quality preservation of specimens. The aim of this work is to report new caviomorph rodents from Salla, and to discuss their systematic and palaeobiogeographical implications in the context of the South American Deseadan caviomorph assemblages. We describe two new genera (†<i>Lapazomys</i> gen. nov. and †<i>Cholamys</i> gen. nov.) and five new species (†<i>Migraveramus lavocati</i> sp. nov., †<i>Sallamys woodi</i> sp. nov., †<i>Lapazomys hartenbergeri</i> sp. nov., †<i>Protosteiromys pattersoni</i> sp. nov. and †<i>Cholamys tetralophodonta</i> sp. nov.). These include the first erethizontids and the oldest Cavioidea <i>sensu stricto</i> for middle and low latitudes. The increase in the number of species corroborates the existence of an important rodent diversification already evidenced in the late early/early late Oligocene. In addition, the new rodents lessen the degree of endemism of the Salla rodent fauna proposed in previous papers. We interpret that the differences among Deseadan assemblages from low, middle and high latitudes are due essentially to climatic, historical and local environmental conditions, whereas diachronism seems less important in the modelling of faunas. http://zoobank.org/urn:lsid:zoobank.org:pub:A8A04332-12E1-4966-9807-47B66554718E
DOI: 10.6084/m9.figshare.6590993
title: Does S100B have a potential role in affective disorders? A literature review

description: <b>Background:</b> S100B is a calcium-binding protein located in glial cells; it is regarded as a potential biomarker in affective disorders. <b>Aim:</b> To review the literature investigating the role of S100B in patients with affective disorders. <b>Method:</b> A systematic review of original English language studies investigating S100B in serum, cerebrospinal fluid, plasma and lymphocytes, in patients with affective disorders, was conducted. The literature search was conducted within the PubMed database. Effect sizes were calculated to adjust for systematic measurement effects. <b>Results:</b> Twenty studies were included, with a total of 1292 participants. Of these, 398 patients had or have had depressive disorder, 301 patients had bipolar disorder and 593 were healthy controls. S100B levels in serum were consistently elevated in studies with statistically significant results which investigated acute affective episodes (comprising major depressive episode in major depressive disorder, and both manic and depressive episodes in patients with bipolar disorder), in comparison to healthy controls. There were few studies assessing S100B levels in cerebrospinal fluid, plasma or lymphocytes, and these had inconsistent results. <b>Conclusion:</b> The results indicated that elevated S100B levels might be associated with mood episodes in affective disorders. However, the role of S100B, and its possible impact in affective disorders, requires further investigation and at the present S100B does not have a role as clinically biomarker in affective disorder. Future longitudinal multicentre studies with larger transdiagnostic real life patient cohorts are warranted.
DOI: 10.6084/m9.figshare.6590993.v1
title: Does S100B have a potential role in affective disorders? A literature review

description: <b>Background:</b> S100B is a calcium-binding protein located in glial cells; it is regarded as a potential biomarker in affective disorders. <b>Aim:</b> To review the literature investigating the role of S100B in patients with affective disorders. <b>Method:</b> A systematic review of original English language studies investigating S100B in serum, cerebrospinal fluid, plasma and lymphocytes, in patients with affective disorders, was conducted. The literature search was conducted within the PubMed database. Effect sizes were calculated to adjust for systematic measurement effects. <b>Results:</b> Twenty studies were included, with a total of 1292 participants. Of these, 398 patients had or have had depressive disorder, 301 patients had bipolar disorder and 593 were healthy controls. S100B levels in serum were consistently elevated in studies with statistically significant results which investigated acute affective episodes (comprising major depressive episode in major depressive disorder, and both manic and depressive episodes in patients with bipolar disorder), in comparison to healthy controls. There were few studies assessing S100B levels in cerebrospinal fluid, plasma or lymphocytes, and these had inconsistent results. <b>Conclusion:</b> The results indicated that elevated S100B levels might be associated with mood episodes in affective disorders. However, the role of S100B, and its possible impact in affective disorders, requires further investigation and at the present S100B does not have a role as clinically biomarker in affective disorder. Future longitudinal multicentre studies with larger transdiagnostic real life patient cohorts are warranted.
DOI: 10.6084/m9.figshare.6590903
title: DNMT1 modulates interneuron morphology by regulating <i>Pak6</i> expression through crosstalk with histone modifications

description: Epigenetic mechanisms of gene regulation, including DNA methylation and histone modifications, call increasing attention in the context of development and human health. Thereby, interactions between DNA methylating enzymes and histone modifications tremendously multiply the spectrum of potential regulatory functions. Epigenetic networks are critically involved in the establishment and functionality of neuronal circuits that are composed of gamma-aminobutyric acid (GABA)-positive inhibitory interneurons and excitatory principal neurons in the cerebral cortex. We recently reported a crucial role of the DNA methyltransferase 1 (DNMT1) during the migration of immature POA-derived cortical interneurons by promoting the migratory morphology through repression of <i>Pak6</i>. However, the DNMT1-dependent regulation of <i>Pak6</i> expression appeared to occur independently of direct DNA methylation. Here, we show that in addition to its DNA methylating activity, DNMT1 can act on gene transcription by modulating permissive H3K4 and repressive H3K27 trimethylation in developing inhibitory interneurons, similar to what was found in other cell types. In particular, the transcriptional control of <i>Pak6</i>, interactions of DNMT1 with the Polycomb-repressor complex 2 (PCR2) core enzyme EZH2, mediating repressive H3K27 trimethylations at regulatory regions of the <i>Pak6</i> gene locus. Similar to what was observed upon <i>Dnmt1</i> depletion, inhibition of EZH2 caused elevated <i>Pak6</i> expression levels accompanied by increased morphological complexity, which was rescued by siRNA-mediated downregulation of <i>Pak6</i> expression. Together, our data emphasise the relevance of DNMT1-dependent crosstalk with histone tail methylation for transcriptional control of genes like <i>Pak6</i> required for proper cortical interneuron migration.