cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5123977
title: Supplementary Material for: <b><i>Francisella </i></b>Is Sensitive to Insect Antimicrobial Peptides

description: <i>Francisella tularensis</i> causes the zoonotic disease tularemia. Arthropod vectors are important transmission routes for the disease, although it is not known how <i>Francisella</i> survives the efficient arthropod immune response. Here, we used <i>Drosophila melanogaster</i> as a model host for <i>Francisella</i> infections and investigated whether the bacteria are resistant to insect humoral immune responses, in particular to the antimicrobial peptides (AMPs) secreted into the insect hemolymph. Moreover, we asked to what extent such resistance might depend on lipopolysaccharide (LPS) structure and surface characteristics of the bacteria. We analyzed <i>Francisella novicida</i> mutant strains in genes, directly or indirectly involved in specific steps of LPS biosynthesis, for virulence in wild-type and <i>Relish</i><sup><i>E20</i></sup> immune-deficient flies, and tested selected mutants for sensitivity to AMPs in vitro. We demonstrate that <i>Francisella</i> is sensitive to specific fly AMPs, i.e. Attacin, Cecropin, Drosocin and Drosomycin. Furthermore, six bacterial genes, <i>kpsF, manB, lpxF, slt, tolA </i>and<i> pal</i>, were found to be required for resistance to <i>Relish</i>-dependent immune responses, illustrating the importance of structural details of <i>Francisella</i> lipid A and Kdo core for interactions with AMPs. Interestingly, a more negative surface charge and lack of O-antigen did not render mutant bacteria more sensitive to cationic AMPs and did not attenuate virulence in flies.
DOI: 10.6084/m9.figshare.5123980
title: Supplementary Material for: Replication of Respiratory Syncytial Virus Is Inhibited by the Host Defense Molecule Viperin

description: Respiratory syncytial virus (RSV) is an important viral pathogen of otitis media, bronchiolitis, and pneumonia. As infection of the upper airways is a precondition for the development of these diseases, understanding RSV pathogenesis and the host response induced by RSV in this niche may enable the development of novel therapeutic strategies against this virus. We have used a microarray approach and showed that expression of the gene that encodes the antiviral protein viperin was significantly upregulated in the chinchilla nasopharynx up to 1 week after RSV challenge. Overexpression of human viperin in vitro diminished the ability of RSV to infect HeLa or A549 cells. Furthermore, transduction of the chinchilla airways with a recombinant adeno-associated virus vector that encodes <i>viperin</i> resulted in reduced titers of RSV in the nasopharyngeal lavage fluid. Collectively, these data indicated that viperin plays a significant role in the innate immune defense against RSV.
DOI: 10.6084/m9.figshare.5123983.v1
title: Supplementary Material for: Simultaneous and Sequential Concurrent Myeloproliferative and Lymphoproliferative Neoplasms

description: Concurrent manifestation of two chronic-stage myeloid and lymphoid/plasmacytoid neoplasms in one patient is rare and occurs in ≤1% of patients. There has been no systematic analysis of which combinations are frequent/infrequent and whether two concurrent diseases in one patient are clonally related or represent independent diseases. We therefore characterised a series of cases from our own archive (n = 65) and collected a large number of previously reported cases of patients in whom myeloid and lymphoid/plasmacytoid neoplasms co-occurred (n = 185). The most frequent combination was Philadelphia chromosome-negative myeloproliferative neoplasm with concurrent B cell chronic lymphocytic leukaemia, accounting for approximately 50% of double-disease patients. We compared the quantity of unsorted bone marrow cell-derived JAK2<sup>V617F</sup> and KIT<sup>D816V</sup> alleles with the quantity of the lymphoid/plasmacytoid compartment and analysed a subfraction of cases with fluorescence in situ hybridisation. Although a common aberrant progenitor has been reported in some cases in the literature, we found evidence of two independent chronic-stage myeloid and lymphoid/plasmacytoid neoplasms.
DOI: 10.6084/m9.figshare.5123986.v1
title: Supplementary Material for: Spinal Transection Induces Widespread Proliferation of Cells along the Length of the Spinal Cord in a Weakly Electric Fish

description: The ability to regenerate spinal cord tissue after tail amputation has been well studied in several species of teleost fish. The present study examined the proliferation and survival of cells following complete spinal cord transection rather than tail amputation in the weakly electric fish <i>Apteronotus leptorhynchus</i>. To quantify cell proliferation along the length of the spinal cord, fish were given a single bromodeoxyuridine (BrdU) injection immediately after spinal transection or sham surgery. Spinal transection significantly increased the density of BrdU<sup>+</sup> cells along the entire length of the spinal cord at 1 day posttransection (dpt), and most newly generated cells survived up to 14 dpt. To examine longer-term survival of the newly proliferated cells, BrdU was injected for 5 days after the surgery, and fish were sacrificed at 14 or 30 dpt. Spinal transection significantly increased cell proliferation and/or survival, as indicated by an elevated density of BrdU<sup>+</sup> cells in the spinal cords of spinally transected compared to sham-operated and intact fish. At 14 dpt, BrdU<sup>+</sup> cells were abundant at all levels of the spinal cord. By 30 dpt, the density of BrdU<sup>+</sup> cells had decreased at all levels of the spinal cord except at the tip of the tail. Thus, newly generated cells in the caudal-most segment of the spinal cord survived longer than those in more rostral segments. Our findings indicate that spinal cord transection stimulates widespread cellular proliferation; however, there were regional differences in the survival of the newly generated cells.
DOI: 10.6084/m9.figshare.5123971
title: Supplementary Material for: Role of TRPC1 and TRPC3 Channels in Contraction and Relaxation of Mouse Thoracic Aorta

description: <b><i>Background/Aims:</i></b> Canonical transient receptor potential (TRPC) channels modulate membrane potential and intracellular Ca<sup>2+</sup>. We examined the role of TRPC1 and TRPC3 channels in vasocontraction and relaxation in mouse aorta. <b><i>Methods:</i></b> Vasocontraction and relaxation of aorta from wild-type (WT), TRPC1 KO and TRPC3 knockout (KO) mice were measured for phenylephrine (Phe) and carbachol (CCh). Intracellular Ca<sup>2+</sup> was measured in primary aorta endothelial cells (EC) and whole cell K<sup>+</sup> current in freshly isolated smooth muscle cells (SMC). <b><i>Results and Conclusion:</i></b> TRPC1 KO aorta showed increased vasocontraction to Phe compared to WT and TRPC3 KO aorta due to diminished role of BK<sub>Ca</sub> channels. BK<sub>Ca</sub> mRNA (aorta) and whole cell current (SMC) were reduced versus WT. Contraction in WT aorta was increased to TRPC1 KO level by BK<sub>Ca</sub> channel inhibition. Relaxation to CCh was reduced in TRPC1 KO and TRPC3 KO aortas with concomitant reduction in EC Ca<sup>2+</sup> response. Pyr3 (TRPC3 blocker) reduced the Ca<sup>2+</sup> response to CCh in EC from WT, but not TRPC3 KO mice. In summary, TRPC1 attenuates receptor-mediated contraction through activation and/or expression of SMC BK<sub>Ca</sub> channels while TRPC3 does not contribute to receptor-mediated constriction. Both TRPC1 and TRPC3 participate in EC Ca<sup>2+</sup> influx and vasorelaxation of aorta.
DOI: 10.6084/m9.figshare.5123974
title: Supplementary Material for: Serum Total Immunoglobulin E Is a Surrogate of Atopy in Adult-Onset Asthma: A Longitudinal Study

description: <b><i>Background:</i></b> Studies have shown that serum total immunoglobulin E (IgE) levels are higher in asthmatics. However, the role of the serum total IgE level, independently from atopy, in adult asthma is not understood. We studied the associations between serum total IgE, the number of sensitizations and the sum of specific IgEs and new-onset asthma using longitudinal data from the European Community Respiratory Health Survey. <b><i>Methods:</i></b> Serum total and specific IgE to 4 common inhalant allergens were measured at baseline in 9,175 participants, with a follow-up of 9 years. Individuals with asthma history and/or asthma symptoms were excluded. Atopy was defined as the presence of at least one specific IgE ≥0.35 kU/l. Total and specific IgEs were regressed against new-onset asthma using multivariate logistic regression with a random intercept for the study centre. <b><i>Results:</i></b> Two hundred and ninety-seven participants had developed asthma during follow-up (incidence rate 5.7 per 1,000 person-years). A 10% higher level of total IgE was associated with a 12% increased risk of new-onset asthma (p = 0.005). However, after adjustment for the number of positive specific IgEs [odds ratio (OR) for multiple sensitization 1.74, 95% confidence interval (CI) 1.05–2.88] and the sum of allergen-specific IgEs (OR 1.18, 95% CI 1.00–1.40), the association between total IgE and asthma disappeared (OR 1.00, 95% CI 0.91–1.10). Seventeen percent of new-onset asthma cases could be attributed to atopy, and this estimate was not largely modified when the total IgE level was simultaneously taken into account. <b><i>Conclusions:</i></b> After taking into account the number and intensity of 4 specific IgEs, the serum total IgE level was not associated with new-onset asthma in adults.
DOI: 10.6084/m9.figshare.5123974.v1
title: Supplementary Material for: Serum Total Immunoglobulin E Is a Surrogate of Atopy in Adult-Onset Asthma: A Longitudinal Study

description: <b><i>Background:</i></b> Studies have shown that serum total immunoglobulin E (IgE) levels are higher in asthmatics. However, the role of the serum total IgE level, independently from atopy, in adult asthma is not understood. We studied the associations between serum total IgE, the number of sensitizations and the sum of specific IgEs and new-onset asthma using longitudinal data from the European Community Respiratory Health Survey. <b><i>Methods:</i></b> Serum total and specific IgE to 4 common inhalant allergens were measured at baseline in 9,175 participants, with a follow-up of 9 years. Individuals with asthma history and/or asthma symptoms were excluded. Atopy was defined as the presence of at least one specific IgE ≥0.35 kU/l. Total and specific IgEs were regressed against new-onset asthma using multivariate logistic regression with a random intercept for the study centre. <b><i>Results:</i></b> Two hundred and ninety-seven participants had developed asthma during follow-up (incidence rate 5.7 per 1,000 person-years). A 10% higher level of total IgE was associated with a 12% increased risk of new-onset asthma (p = 0.005). However, after adjustment for the number of positive specific IgEs [odds ratio (OR) for multiple sensitization 1.74, 95% confidence interval (CI) 1.05–2.88] and the sum of allergen-specific IgEs (OR 1.18, 95% CI 1.00–1.40), the association between total IgE and asthma disappeared (OR 1.00, 95% CI 0.91–1.10). Seventeen percent of new-onset asthma cases could be attributed to atopy, and this estimate was not largely modified when the total IgE level was simultaneously taken into account. <b><i>Conclusions:</i></b> After taking into account the number and intensity of 4 specific IgEs, the serum total IgE level was not associated with new-onset asthma in adults.
DOI: 10.6084/m9.figshare.5123977.v1
title: Supplementary Material for: <b><i>Francisella </i></b>Is Sensitive to Insect Antimicrobial Peptides

description: <i>Francisella tularensis</i> causes the zoonotic disease tularemia. Arthropod vectors are important transmission routes for the disease, although it is not known how <i>Francisella</i> survives the efficient arthropod immune response. Here, we used <i>Drosophila melanogaster</i> as a model host for <i>Francisella</i> infections and investigated whether the bacteria are resistant to insect humoral immune responses, in particular to the antimicrobial peptides (AMPs) secreted into the insect hemolymph. Moreover, we asked to what extent such resistance might depend on lipopolysaccharide (LPS) structure and surface characteristics of the bacteria. We analyzed <i>Francisella novicida</i> mutant strains in genes, directly or indirectly involved in specific steps of LPS biosynthesis, for virulence in wild-type and <i>Relish</i><sup><i>E20</i></sup> immune-deficient flies, and tested selected mutants for sensitivity to AMPs in vitro. We demonstrate that <i>Francisella</i> is sensitive to specific fly AMPs, i.e. Attacin, Cecropin, Drosocin and Drosomycin. Furthermore, six bacterial genes, <i>kpsF, manB, lpxF, slt, tolA </i>and<i> pal</i>, were found to be required for resistance to <i>Relish</i>-dependent immune responses, illustrating the importance of structural details of <i>Francisella</i> lipid A and Kdo core for interactions with AMPs. Interestingly, a more negative surface charge and lack of O-antigen did not render mutant bacteria more sensitive to cationic AMPs and did not attenuate virulence in flies.
DOI: 10.6084/m9.figshare.5123962
title: Supplementary Material for: Accessing Carboxylesterase Diversity from Termite Hindgut Symbionts through Metagenomics

description: A shotgun metagenomic library was constructed from termite hindgut symbionts and subsequently screened for esterase activities. A total of 68 recombinant clones conferring esterolytic phenotypes were identified, of which the 14 most active were subcloned and sequenced. The nucleotide lengths of the esterase-encoding open reading frames (ORFs) ranged from 783 to 2,592 bp and encoded proteins with predicted molecular masses of between 28.8 and 97.5 kDa. The highest identity scores in the GenBank database, from a global amino acid alignment ranged from 39 to 83%. The identified ORFs revealed the presence of the G-X-S-X-D, G-D-S-X, and S-X-X-K sequence motifs that have been reported to harbour a catalytic serine residue in other previously reported esterase primary structures. Five of the ORFs (EstT5, EstT7, EstT9, EstT10, and EstT12) could not be classified into any of the original eight esterase families. One of the ORFs (EstT9) showed a unique primary structure consisting of an amidohydrolase-esterase fusion. Six of the 14 esterase-encoding genes were recombinantly expressed in <i>Escherichia coli</i> and the purified enzymes exhibited temperature optima of between 40–50°C. Substrate-profiling studies revealed that the characterised enzymes were ‘true’ carboxylesterases based on their preferences for short to medium chain length <i>p</i>-nitrophenyl ester substrates. This study has demonstrated a successful application of a metagenomic approach in accessing novel esterase-encoding genes from the gut of termites that could otherwise have been missed by classical culture enrichment approaches.
DOI: 10.6084/m9.figshare.5123965
title: Supplementary Material for: Reduction in Body Weight but Worsening Renal Function with Late Ultrafiltration for Treatment of Acute Decompensated Heart Failure

description: <b><i>Objectives:</i></b> The safety, effectiveness and indications for ultrafiltration (UF) are not well established. We hypothesized that UF would not worsen renal function in patients with heart failure (HF) who were not responding to medical therapy. <b><i>Methods:</i></b> Data was collected for patients who underwent UF between 2006 and 2010 (n = 72, median age 61 years, 54% males, 61% Caucasian, 54% left ventricular ejection fraction ≥40%). <b><i>Results:</i></b> Baseline GFR was 38 ml/min/ 1.73 m<sup>2</sup>. All patients were initially treated with loop diuretics and 58% required a thiazide-like diuretic or vasoactive agent. UF resulted in total fluid removal of 11.3 liters and weight loss was 9.7 kg. The median decrease in eGFR during UF was 4.5 ml/min/m<sup>2</sup> (IQR –13, 0; p &lt;0.01) and 43% of patients experienced a ≥20% decrease in eGFR. Ten percent of patients required dialysis and 13% died, received a ventricular assist device/cardiac transplant or were discharged to hospice. <b><i>Conclusions:</i></b> In a cohort of HF patients who did not respond to medical therapy, UF was associated not only with a significant reduction of body weight and fluid removal, but also acute worsening of renal function. Further research to identify the appropriate population for UF, long-term outcomes and the intensity of treatment is required if UF is to gain wide acceptance for HF management.
DOI: 10.6084/m9.figshare.5123959
title: Supplementary Material for: Identification of Interstitial Cajal-Like Cells in the Human Thoracic Duct

description: Interstitial Cajal-like cells (ICLCs) are speculated to be pacemakers in smooth muscle tissues. While the human thoracic duct (TD) is spontaneously active, the origin of this activity is unknown. We hypothesized that ICLCs could be present in the TD and using histological techniques, immunohistochemistry and immunofluorescence we have investigated the presence of ICLCs, protein markers for ICLCs and the cellular morphology of the human TD. Transmission electron microscopy was employed to investigate ultrastructure. Methylene blue staining, calcium-dependent fluorophores and confocal microscopy were used to identify ICLCs in live tissue. Methylene blue stained cells with morphology suggestive of ICLCs in the TD. Immunoreactivity localized the ICLC protein markers c-kit, CD34 and vimentin to many cells and processes associated with smooth muscle cells (SMCs): coexpression of c-kit with vimentin or CD34 was observed in some cells. Electron microscopy analysis confirmed ICLCs as a major cell type of the human TD. Lymphatic ICLCs possess caveolae, dense bands, a patchy basal lamina, intermediate filaments and specific junctions to SMCs. ICLCs were ultrastructurally differentiable from other interstitial cells observed: fibroblasts, mast cells, macrophages and pericytes. Lymphatic ICLCs were localized to the subendothelial region of the wall as well as in intimate association with smooth muscle bundles throughout the media. ICLCs were morphologically distinct with multiple processes and also spindle shapes. Confocal imaging with calcium-dependent fluorophores corroborated cell morphology and localization observed in fixed tissues. Lymphatic ICLCs thus constitute a significant cell type of the human TD and physically interact with lymphatic SMCs.
DOI: 10.6084/m9.figshare.5123965.v1
title: Supplementary Material for: Reduction in Body Weight but Worsening Renal Function with Late Ultrafiltration for Treatment of Acute Decompensated Heart Failure

description: <b><i>Objectives:</i></b> The safety, effectiveness and indications for ultrafiltration (UF) are not well established. We hypothesized that UF would not worsen renal function in patients with heart failure (HF) who were not responding to medical therapy. <b><i>Methods:</i></b> Data was collected for patients who underwent UF between 2006 and 2010 (n = 72, median age 61 years, 54% males, 61% Caucasian, 54% left ventricular ejection fraction ≥40%). <b><i>Results:</i></b> Baseline GFR was 38 ml/min/ 1.73 m<sup>2</sup>. All patients were initially treated with loop diuretics and 58% required a thiazide-like diuretic or vasoactive agent. UF resulted in total fluid removal of 11.3 liters and weight loss was 9.7 kg. The median decrease in eGFR during UF was 4.5 ml/min/m<sup>2</sup> (IQR –13, 0; p &lt;0.01) and 43% of patients experienced a ≥20% decrease in eGFR. Ten percent of patients required dialysis and 13% died, received a ventricular assist device/cardiac transplant or were discharged to hospice. <b><i>Conclusions:</i></b> In a cohort of HF patients who did not respond to medical therapy, UF was associated not only with a significant reduction of body weight and fluid removal, but also acute worsening of renal function. Further research to identify the appropriate population for UF, long-term outcomes and the intensity of treatment is required if UF is to gain wide acceptance for HF management.
DOI: 10.6084/m9.figshare.5123980.v1
title: Supplementary Material for: Replication of Respiratory Syncytial Virus Is Inhibited by the Host Defense Molecule Viperin

description: Respiratory syncytial virus (RSV) is an important viral pathogen of otitis media, bronchiolitis, and pneumonia. As infection of the upper airways is a precondition for the development of these diseases, understanding RSV pathogenesis and the host response induced by RSV in this niche may enable the development of novel therapeutic strategies against this virus. We have used a microarray approach and showed that expression of the gene that encodes the antiviral protein viperin was significantly upregulated in the chinchilla nasopharynx up to 1 week after RSV challenge. Overexpression of human viperin in vitro diminished the ability of RSV to infect HeLa or A549 cells. Furthermore, transduction of the chinchilla airways with a recombinant adeno-associated virus vector that encodes <i>viperin</i> resulted in reduced titers of RSV in the nasopharyngeal lavage fluid. Collectively, these data indicated that viperin plays a significant role in the innate immune defense against RSV.
DOI: 10.6084/m9.figshare.5123953
title: Supplementary Material for: A Problem Shared Is a Problem Reduced: Seeking Efficiency in the Conservation of Felids and Primates

description: Threats faced by mammalian species can be grouped into one of a handful of categories, such as habitat loss, unsustainable hunting and persecution. Insofar as they face common threats, diverse species may benefit from the same conservation intervention, thereby offering efficiencies in conservation action. We explore this proposition for primates and felids by examining coarse scale overlaps in geographical distributions, using IUCN Red List assessments of the primary threats posed to each species. A global analysis of primates and felids that face common threats reveals the greatest overlap is in Central and South Asia, where up to 14 primates and felids co-occur. More than 80% of the land where at least 1 threatened species of either primate or felid occurs also contains at least one threatened species of the other taxon, yet over 60% of these grid cells containing both threatened primates and felids lie outside Conservation International’s hot spots. A review of IUCN Action Plans of the threats to felids and primates strongly supports the hypothesis that they are often the same and occur in the same place. In principle, steps to conserve big cats have the potential to benefit several species of threatened primates, and vice versa.