cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5123476
title: Supplementary Material for: Comparative Genomic Analysis Reveals Novel Facts about <b><i>Leptospirillum</i></b> spp. Cytochromes

description: Chemolithoautotrophic acidophilic bacteria, which belong to the genus <i>Leptospirillum</i>, can only grow with Fe(II) as electron donor and oxygen as an electron acceptor. Members of this genus play an important role in bioleaching sulfide ores. We used nearly complete genome sequences of <i>Leptospirillum ferrooxidans</i> (group I), <i>Leptospirillum rubarum, Leptospirillum</i> ‘5-way CG’ (group II) and <i>Leptospirillum ferrodia</i><i>zotrophum</i> (group III) to identify cytochromes that are likely involved in electron transfer chain(s). The results show the presence of genes encoding a number of <i>c</i>-type cytochromes (18–20 genes were identified in each species), as well as <i>bd</i> and <i>cbb</i><sub><i>3</i></sub> oxidases. Genes encoding <i>cbb</i><sub><i>3</i></sub> oxidase are clustered, with predicted genes involved in <i>cbb</i><sub><i>3</i></sub> maturation proteins. Duplication of <i>cbb</i><sub><i>3</i></sub> encoding genes (<i>ccoNO)</i> was detected in all four genomes. Interestingly, these micro-organisms also contain genes that potentially encode <i>bc</i><sub><i>1 </i></sub><i>and b</i><sub><i>6</i></sub><i>f-like</i> complexes organized into two putative operon structures. To date, the <i>Leptospirillum </i>genus includes the only organisms reported to have genes coding for two different <i>bc </i>complexes. This study provides detailed insights into the components of electron transfer chains of <i>Leptospirillum</i> spp., revealing their conservation among leptospirilla groups and suggesting that there may be a single common pathway for electron transport between Fe(II) and oxygen.
DOI: 10.6084/m9.figshare.5123479
title: Supplementary Material for: Activation of MAPK/PI3K/SMAD Pathways by TGF-β<sub>1</sub> Controls Differentiation of Radial Glia into Astrocytes in vitro

description: The major neural stem cell population in the developing cerebral cortex is the radial glia cells, which generate neurons and glial cells. The mechanisms that modulate the maintenance of the radial glia stem cell phenotype, or its differentiation, are not completely elucidated. We previously demonstrated that transforming growth factor-β<sub>1</sub> (TGF-β<sub>1</sub>) promotes radial glia differentiation into astrocytes in vitro [Glia 2007;55:1023–1033]. Here we investigated the intracellular signaling pathways involved in the TGF-β<sub>1</sub>-induced radial glia fate commitment. We demonstrate that the mechanisms underlying the TGF-β<sub>1</sub> effect on radial glia cell differentiation or progenitor potential maintenance diverge. Whereas radial glia differentiation into astrocytes is mediated by the activation of the MAPK signaling pathway, neurogenesis is modulated by different levels of PI3K and SMAD2/3 activity. Our work demonstrates that radial glia cells are a heterogeneous population and a potential target of TGF-β<sub>1</sub>, and suggests that its effect on radial glia fate commitment is mediated by the recruitment of a complex multipathway mechanism that controls astrocyte and neuronal generation in the developing cerebral cortex.
DOI: 10.6084/m9.figshare.5123482
title: Supplementary Material for: An Asthma Action Plan Created by Physician, Educator and Patient Online Collaboration with Usability and Visual Design Optimization

description: <b><i>Background:</i></b> Asthma action plans (AAPs), which decrease hospitalizations and improve symptom control, are recommended in guidelines, but are seldom delivered to patients. Existing AAPs have been developed by experts, without the inclusion of all stakeholders (such as patients with asthma) and without specifically addressing usability and visual design. <b><i>Objective:</i></b> Our objective was to develop a more usable AAP by involving all stakeholders and considering design preferences. <b><i>Methods:</i></b> We created a Wiki-based system for multiuser AAP development. Pulmonologists, primary care physicians, asthma educators and patients used the system to collaboratively compile a single AAP by making multiple online selections over 1 week. We combined common elements from 3 AAPs developed in this way into 1, optimized visual design features and tested face validity in focus groups. <b><i>Results:</i></b> A total of 41 participants averaged 646 selections/week over a login-time of 28.8 h/week. Of 35 participants, 28 (80%) were satisfied with the final AAP and 32 (91%) perceived that they would be able to use it. The plans created by the 3 groups were very similar, with a unanimous or majority agreement in the handling of 100/110 (91%) AAP options. <b><i>Conclusions:</i></b> Inclusion of multiple stakeholders and focus on design preferences predict enhanced usability and uptake of medical tools. The validity of our AAP is further supported by the similarity between the AAPs created by each group, user engagement and satisfaction with the plan and agreement with existing validity criteria proposed by experts. This AAP can be implemented in care with a concurrent measurement of uptake and health impact.
DOI: 10.6084/m9.figshare.5123485
title: Supplementary Material for: A Familial History of Pulmonary Fibrosis in Patients with Chronic Hypersensitivity Pneumonitis

description: <b><i>Background:</i></b> Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease induced by the inhalation of a variety of antigens. Patients with chronic HP often have a family history of pulmonary fibrosis. This strongly suggests that both genetic and environmental factors play an important role in the pathogenesis of chronic HP. <b><i>Objectives:</i></b> We aimed to investigate the epidemiology and clinical features of chronic HP patients with a family history of pulmonary fibrosis. <b><i>Methods:</i></b> We retrospectively reviewed the clinical information of 114 cases diagnosed with chronic HP with insidious onset between 1992 and 2009. <b><i>Results:</i></b> Twenty cases (17.5%) were identified as having a family history of pulmonary fibrosis. All of these patients had lived apart from their afflicted relatives for at least several decades. The familial cases were younger than the nonfamilial cases at onset (57.5 ± 9.6 vs. 64.0 ± 7.0 years old, p = 0.008). The predicted vital capacity percentage and partial pressure of oxygen in arterial blood gas were significantly higher in the familial cases. There were no differences between the 2 groups in gender, smoking history, bronchoalveolar lavage fluid profile, radiologic findings or other clinical features. <b><i>Conclusions:</i></b> We found a familial clustering in patients with chronic HP. Various factors including genetic susceptibility to pulmonary fibrosis and environmental factors may contribute to the development of familial chronic HP.
DOI: 10.6084/m9.figshare.5123473
title: Supplementary Material for: Effect of Postnatal Intermittent Hypoxia on Growth and Cardiovascular Regulation of Rat Pups

description: <b><i>Background:</i></b> Intermittent hypoxic episodes are common among preterm infants, although longer term consequences on growth pattern and cardiovascular regulation are unclear. Furthermore, the effects of intermittent hypoxia (IH) may depend on the pattern of hypoxia-reoxygenation. <b><i>Objectives:</i></b> We tested the hypothesis that a clustered versus dispersed pattern of repetitive IH during early postnatal life would induce differential long-term alteration in growth and cardiovascular regulation. <b><i>Methods:</i></b> Sprague-Dawley rat pups were exposed to room air or to one of two patterns of IH (clustered vs. dispersed) from 1 to 7 days of life. Body weight was measured daily for the first 8 days and weekly from weeks 2 to 8. Blood pressure (BP) and heart rate were measured weekly from weeks 4 to 8 using a noninvasive tail-cuff method for awake, nonanesthetized animals. <b><i>Results:</i></b> Exposure to both patterns of repetitive IH induced early growth restriction followed by later catch-up of growth to controls 3 weeks after completion of IH exposures. IH-exposed rats exhibited a sustained decrease in heart rate regardless of the hypoxic exposure paradigm employed. In contrast, a differential response was seen for arterial pressure; the clustered paradigm was associated with a significantly lower BP versus controls, while the pups exposed to the dispersed paradigm showed no effect on BP. <b><i>Conclusion:</i></b> We speculate that repetitive IH during a critical developmental window and regardless of IH exposure paradigm contributes to prolonged changes in sympathovagal balance of cardiovascular regulation.
DOI: 10.6084/m9.figshare.5123479.v1
title: Supplementary Material for: Activation of MAPK/PI3K/SMAD Pathways by TGF-β<sub>1</sub> Controls Differentiation of Radial Glia into Astrocytes in vitro

description: The major neural stem cell population in the developing cerebral cortex is the radial glia cells, which generate neurons and glial cells. The mechanisms that modulate the maintenance of the radial glia stem cell phenotype, or its differentiation, are not completely elucidated. We previously demonstrated that transforming growth factor-β<sub>1</sub> (TGF-β<sub>1</sub>) promotes radial glia differentiation into astrocytes in vitro [Glia 2007;55:1023–1033]. Here we investigated the intracellular signaling pathways involved in the TGF-β<sub>1</sub>-induced radial glia fate commitment. We demonstrate that the mechanisms underlying the TGF-β<sub>1</sub> effect on radial glia cell differentiation or progenitor potential maintenance diverge. Whereas radial glia differentiation into astrocytes is mediated by the activation of the MAPK signaling pathway, neurogenesis is modulated by different levels of PI3K and SMAD2/3 activity. Our work demonstrates that radial glia cells are a heterogeneous population and a potential target of TGF-β<sub>1</sub>, and suggests that its effect on radial glia fate commitment is mediated by the recruitment of a complex multipathway mechanism that controls astrocyte and neuronal generation in the developing cerebral cortex.
DOI: 10.6084/m9.figshare.5123485.v1
title: Supplementary Material for: A Familial History of Pulmonary Fibrosis in Patients with Chronic Hypersensitivity Pneumonitis

description: <b><i>Background:</i></b> Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease induced by the inhalation of a variety of antigens. Patients with chronic HP often have a family history of pulmonary fibrosis. This strongly suggests that both genetic and environmental factors play an important role in the pathogenesis of chronic HP. <b><i>Objectives:</i></b> We aimed to investigate the epidemiology and clinical features of chronic HP patients with a family history of pulmonary fibrosis. <b><i>Methods:</i></b> We retrospectively reviewed the clinical information of 114 cases diagnosed with chronic HP with insidious onset between 1992 and 2009. <b><i>Results:</i></b> Twenty cases (17.5%) were identified as having a family history of pulmonary fibrosis. All of these patients had lived apart from their afflicted relatives for at least several decades. The familial cases were younger than the nonfamilial cases at onset (57.5 ± 9.6 vs. 64.0 ± 7.0 years old, p = 0.008). The predicted vital capacity percentage and partial pressure of oxygen in arterial blood gas were significantly higher in the familial cases. There were no differences between the 2 groups in gender, smoking history, bronchoalveolar lavage fluid profile, radiologic findings or other clinical features. <b><i>Conclusions:</i></b> We found a familial clustering in patients with chronic HP. Various factors including genetic susceptibility to pulmonary fibrosis and environmental factors may contribute to the development of familial chronic HP.
DOI: 10.6084/m9.figshare.5123482.v1
title: Supplementary Material for: An Asthma Action Plan Created by Physician, Educator and Patient Online Collaboration with Usability and Visual Design Optimization

description: <b><i>Background:</i></b> Asthma action plans (AAPs), which decrease hospitalizations and improve symptom control, are recommended in guidelines, but are seldom delivered to patients. Existing AAPs have been developed by experts, without the inclusion of all stakeholders (such as patients with asthma) and without specifically addressing usability and visual design. <b><i>Objective:</i></b> Our objective was to develop a more usable AAP by involving all stakeholders and considering design preferences. <b><i>Methods:</i></b> We created a Wiki-based system for multiuser AAP development. Pulmonologists, primary care physicians, asthma educators and patients used the system to collaboratively compile a single AAP by making multiple online selections over 1 week. We combined common elements from 3 AAPs developed in this way into 1, optimized visual design features and tested face validity in focus groups. <b><i>Results:</i></b> A total of 41 participants averaged 646 selections/week over a login-time of 28.8 h/week. Of 35 participants, 28 (80%) were satisfied with the final AAP and 32 (91%) perceived that they would be able to use it. The plans created by the 3 groups were very similar, with a unanimous or majority agreement in the handling of 100/110 (91%) AAP options. <b><i>Conclusions:</i></b> Inclusion of multiple stakeholders and focus on design preferences predict enhanced usability and uptake of medical tools. The validity of our AAP is further supported by the similarity between the AAPs created by each group, user engagement and satisfaction with the plan and agreement with existing validity criteria proposed by experts. This AAP can be implemented in care with a concurrent measurement of uptake and health impact.
DOI: 10.6084/m9.figshare.5123464
title: Supplementary Material for: Differential Sirtuin Expression Patterns in Amyotrophic Lateral Sclerosis (ALS) Postmortem Tissue: Neuroprotective or Neurotoxic Properties of Sirtuins in ALS?

description: <b><i>Background/Aims:</i></b> Sirtuins (SIRT1–7; class III histone deactylases) modulate fundamental mechanisms in age-related neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). We assessed the expression levels of sirtuins in human postmortem ALS and control brain and spinal cord. <b><i>Methods and Results:</i></b> By quantitative real-time PCR, a significant reduction of SIRT1 and SIRT2 was detected in homogenates of the primary motor cortex (white and gray matter), while there were no differences in spinal cord homogenates. When specifically analyzing mRNA and protein expression in the gray matter (cortical layers I–VI of the precentral gyrus, ventral/dorsal horn of the spinal cord) by in situ hybridization histochemistry and immunohistochemistry, we found increased levels of SIRT1, SIRT2 and SIRT5 in ALS which were significant for SIRT1 and SIRT5 mRNA in the spinal cord. <b><i>Conclusion:</i></b> Our results indicate a general reduction of SIRT1 and SIRT2 in ALS primary motor cortex, while in situ hybridization histochemistry and immunohistochemistry showed neuron-specific upregulation of SIRT1, SIRT2 and SIRT5, particularly in the spinal cord. Opposed effects have been described for SIRT1 and SIRT2: while SIRT1 activation is mainly associated with neuroprotection, SIRT2 upregulation is toxic to neuronal cells. Novel therapeutic approaches in ALS could therefore target SIRT1 activation or SIRT2 inhibition.
DOI: 10.6084/m9.figshare.5123470
title: Supplementary Material for: Hypothalamic Deep Brain Stimulation Influences Autonomic and Limbic Circuitry Involved in the Regulation of Aggression and Cardiocerebrovascular Control in the Göttingen Minipig

description: <b><i>Background:</i></b> Deep brain stimulation (DBS) in the ventral tuberal hypothalamus (VTH) is currently under investigation for the treatment of severe obesity. Stimulation impact on a number of closely related hypothalamic neural systems could potentially influence normal hypothalamic function and thereby generate adverse side effects. <b><i>Objective:</i></b> To assess the feasibility and safety of VTH DBS in a non-primate large animal model. <b><i>Methods:</i></b> In the VTH of 6 Göttingen minipigs, quadropolar leads were implanted bilaterally (n = 2) or unilaterally (n = 4), using optimized MRI sequences allowing identification of major diencephalic landmarks. Heart rate, weight, behavior and nighttime locomotor activity were recorded throughout the study period. Two of the unilaterally implanted minipigs were examined with [<sup>15</sup>O]H<sub>2</sub>O positron emission tomography (PET) scans performed in DBS-off and DBS-on mode. <b><i>Results:</i></b> VTH DBS elicited an amplitude-dependent increase in heart rate and transient aggressive behavior. PET demonstrated that VTH DBS caused a global increase in cerebral blood flow velocities and decreased mean transit time. <b><i>Conclusions:</i></b> VTH DBS results in behavioral and physiological changes, which may derive from activation of closely related limbic and autonomic networks. Caution and further studies of longer length should be requested before this procedure is used more widely in humans.
DOI: 10.6084/m9.figshare.5123461
title: Supplementary Material for: How Does Inhibition of the Renin-Angiotensin System Affect the Prognosis of Advanced Gastric Cancer Patients Receiving Platinum-Based Chemotherapy?

description: <b><i>Background:</i></b> The renin-angiotensin system (RAS) is related to the regulation of cell proliferation, angiogenesis, and tumor progression. <b><i>Patients and Methods:</i></b> We retrospectively analyzed the effect of angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) in 63 patients with advanced gastric cancer (AGC) with platinum-based chemotherapy. All patients analyzed had received medications for hypertension at the diagnosis of AGC. Patients were divided into two groups: an ACEI/ARB group (n = 30) and a non-ACEI/ARB group (n = 33). <b><i>Results:</i></b> Patient characteristics were not different between patients with and without ACEI/ARB. The response rate for all patients was 25.4% and the disease control rate was 77.8%. The median progression-free survival (PFS) for first-line chemotherapy was 5.5 months (95% CI 3.71–7.29) in the ACEI/ARB group and 4.3 months (95% CI 2.39–6.21) in the non-ACEI/ARB group (p = 0.506). There was a significant difference in overall survival (OS) in the ACEI/ARB group compared to the non-ACEI/ARB group (median OS: 8.2 vs. 13.9, p = 0.0095). In multivariate analysis, the use of ACEI/ARB was a significant independent prognostic factor for OS (p = 0.039) but not for PFS. <b><i>Conclusion:</i></b> ACEI/ARB in combination with standard chemotherapy might improve survival in patients with AGC and hypertension. These results support further investigation into the anticancer effects of ACEL/ARB.
DOI: 10.6084/m9.figshare.5123467
title: Supplementary Material for: Altered in vitro Proliferation of Mouse SOD1-G93A Skeletal Muscle Satellite Cells

description: <b><i>Background:</i></b> Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neurodegenerative disease characterized by ascending muscle weakness, atrophy and paralysis. Early muscle abnormalities that precede motor neuron loss in ALS may destabilize neuromuscular junctions, and we have previously demonstrated alterations in myogenic regulatory factor (MRF) expression in vivo and in the activation of myofiber-associated skeletal muscle satellite cells (SMSCs) in the mouse model of ALS (SOD1-G93A). <b><i>Methods:</i></b> To elucidate niche dependence versus cell-autonomous mutant SOD1 (mSOD1) toxicity in this model, we measured in vitro proliferation potential and MRF and cyclin gene expression in SMSC cultures derived from fast-twitch extensor digitorum longus and slow-twitch soleus muscles of SOD1-G93A mice. <b><i>Results:</i></b> SMSCs from early presymptomatic (p40) to terminal, semi-paralytic (p120) SOD1-G93A mice demonstrated generally lower proliferation potential compared with age-matched controls. However, induced proliferation was observed in surgically denervated wild-type animals and SOD1-G93A animals at p90, when critical denervation arises. SMSCs from fast and slow muscles were similarly affected by mSOD1 expression. Lowered proliferation rate was generally corroborated with decreased relative MRF expression levels, although this was most prominent in early age and was modulated by muscle type origin. Cyclins controlling cell proliferation did not show modifications in their mRNA levels; however, the expression of cyclin-dependent kinase inhibitor 1A <i>(Cdkn1a)</i>, which is known to promote myoblast differentiation, was decreased in SOD1-G93A cultures. <b><i>Conclusions:</i></b> Our data suggest that the function of SMSCs is impaired in SOD1-G93A satellite cells from the earliest stages of the disease when no critical motor neuron loss has been described.
DOI: 10.6084/m9.figshare.5123473.v1
title: Supplementary Material for: Effect of Postnatal Intermittent Hypoxia on Growth and Cardiovascular Regulation of Rat Pups

description: <b><i>Background:</i></b> Intermittent hypoxic episodes are common among preterm infants, although longer term consequences on growth pattern and cardiovascular regulation are unclear. Furthermore, the effects of intermittent hypoxia (IH) may depend on the pattern of hypoxia-reoxygenation. <b><i>Objectives:</i></b> We tested the hypothesis that a clustered versus dispersed pattern of repetitive IH during early postnatal life would induce differential long-term alteration in growth and cardiovascular regulation. <b><i>Methods:</i></b> Sprague-Dawley rat pups were exposed to room air or to one of two patterns of IH (clustered vs. dispersed) from 1 to 7 days of life. Body weight was measured daily for the first 8 days and weekly from weeks 2 to 8. Blood pressure (BP) and heart rate were measured weekly from weeks 4 to 8 using a noninvasive tail-cuff method for awake, nonanesthetized animals. <b><i>Results:</i></b> Exposure to both patterns of repetitive IH induced early growth restriction followed by later catch-up of growth to controls 3 weeks after completion of IH exposures. IH-exposed rats exhibited a sustained decrease in heart rate regardless of the hypoxic exposure paradigm employed. In contrast, a differential response was seen for arterial pressure; the clustered paradigm was associated with a significantly lower BP versus controls, while the pups exposed to the dispersed paradigm showed no effect on BP. <b><i>Conclusion:</i></b> We speculate that repetitive IH during a critical developmental window and regardless of IH exposure paradigm contributes to prolonged changes in sympathovagal balance of cardiovascular regulation.