cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5125762
title: Supplementary Material for: Karyological Characterization of the Endemic Iberian Rock Lizard, <b><i>Iberolacerta monticola</i></b> (Squamata, Lacertidae): Insights into Sex Chromosome Evolution

description: Rock lizards of the genus <i>Iberolacerta</i> constitute a promising model to examine the process of sex chromosome evolution, as these closely related taxa exhibit remarkable diversity in the degree of sex chromosome differentiation with no clear phylogenetic segregation, ranging from cryptic to highly heteromorphic ZW chromosomes and even multiple chromosome systems (Z<sub>1</sub>Z<sub>1</sub>Z<sub>2</sub>Z<sub>2</sub>/Z<sub>1</sub>Z<sub>2</sub>W). To gain a deeper insight into the patterns of karyotype and sex chromosome evolution, we performed a cytogenetic analysis based on conventional staining, banding techniques and fluorescence in situ hybridization in the species <i>I. monticola</i>, for which previous cytogenetic investigations did not detect differentiated sex chromosomes. The karyotype is composed of 2n = 36 acrocentric chromosomes. NORs and the major ribosomal genes were located in the subtelomeric region of chromosome pair 6. Hybridization signals of the telomeric sequences (TTAGGG)<sub>n</sub> were visualized at the telomeres of all chromosomes and interstitially in 5 chromosome pairs. C-banding showed constitutive heterochromatin at the centromeres of all chromosomes, as well as clear pericentromeric and light telomeric C-bands in several chromosome pairs. These results highlight some chromosomal markers which can be useful to identify species-specific diagnostic characters, although they may not accurately reflect the phylogenetic relationships among the taxa. In addition, C-banding revealed the presence of a heteromorphic ZW sex chromosome pair, where W is smaller than Z and almost completely heterochromatic. This finding sheds light on sex chromosome evolution in the genus <i>Iberolacerta</i> and suggests that further comparative cytogenetic analyses are needed to understand the processes underlying the origin, differentiation and plasticity of sex chromosome systems in lacertid lizards.
DOI: 10.6084/m9.figshare.5125753
title: Supplementary Material for: Dialysis Dose and Intradialytic Hypotension: Results from the HEMO Study

description: <b><i>Background:</i></b> Intradialytic hypotension (IDH) is common and is associated with increased morbidity and mortality in chronic hemodialysis patients. A higher dialysis ‘dose' may generate transient intradialytic osmotic gradients, predisposing to intracellular fluid shifts and resulting in hypotension. <b><i>Study Design:</i></b> We performed a post hoc analysis of the HEMO study, a multicenter trial that randomized chronic hemodialysis patients to high versus standard Kt/V and higher versus lower membrane flux. In order to achieve dose targets, per protocol, adjustments were made in membrane efficiency, blood flow or dialysate flow before changing session length. Detailed hemodynamic and urea kinetic modeling data were abstracted from 1,825 individuals. The primary outcome was the occurrence of hypotensive events necessitating clinical intervention (saline infusion, lowering of ultrafiltration rate or reduced blood flow). <b><i>Results:</i></b> Intradialytic hypotensive events occurred more frequently in the higher-Kt/V group (18.3 vs. 16.8%; p &lt; 0.001). Participants randomized to higher-target Kt/V had a greater adjusted risk of IDH than those randomized to standard Kt/V [odds ratio (OR) 1.12; 95% confidence interval (CI) 1.01-1.25]. Higher vs. lower dialyzer mass transfer-area coefficient for urea and rate of urea removal were associated with greater adjusted odds of IDH (OR 1.15; 95% CI 1.04-1.27 and OR 1.05; 95% CI 1.04-1.06 per mg/dl/h, respectively). <b><i>Conclusions:</i></b> Higher dialysis dose, at relatively constrained treatment times, may associate with an increased risk of IDH. These findings support the possibility that rapidity of intradialytic reductions in plasma osmolality may play an important role in mediating hemodynamic instability during dialysis.
DOI: 10.6084/m9.figshare.5125759
title: Supplementary Material for: An Integrated Stroke Model with a Consistent Penumbra for the Assessment of Neuroprotective Interventions

description: <b><i>Background/Aim:</i></b> A longer period of vessel occlusion reduces the coefficient of variation of the infarct lesion size [‘infarct variation coefficient' (IVC)] due to a gradual expansion of the lesion within a limited territory defined by the vascular anatomy, but it increases the mortality rate. A crucial issue in the induction of experimental focal cerebral ischemia has been to achieve a low IVC value and a low mortality rate. We attempted to improve IVC and mortality using the 3-vessel occlusion model. <b><i>Methods:</i></b> We introduced a new, transtemporal fascia approach to expose the zygomatic arch, in which the fascia of the temporal muscle is cut and retracted dorsally together with the facial nerve and the vein en bloc. <b><i>Results/Conclusion:</i></b> The approach avoided traumatic venous bleeding around the zygomatic arch. We established a bloodless model of focal ischemia that can produce a consistent degree of reduction in the regional cerebral blood flow within the ischemic penumbra. The model, characterized by a 15-min ischemia, an IVC of 15-21%, and low mortality after ischemia, is expected to produce reliable preclinical evidence in the assessment of neuroprotective interventions for ischemic stroke. The entire procedure is presented in the online supplementary video (www. karger.com/doi/10.1159/000356048).
DOI: 10.6084/m9.figshare.5125750
title: Supplementary Material for: Dissemination and Implementation of the ARIA Guidelines for Allergic Rhinitis in General Practice

description: <b><i>Background:</i></b> Allergic rhinitis (AR) is a prevalent problem in general practice. The first evidence-based guidelines for AR, the ARIA guidelines, were published and have been updated repeatedly since 2001 in order to improve the care of AR patients. Very limited information, however, is available on the impact of these guidelines on everyday clinical practice. The aim of this study was to evaluate the dissemination and implementation of the ARIA guidelines in general practice. <b><i>Methods:</i></b> Three hundred and fifty Flemish general practitioners (GPs) were recruited to complete a questionnaire covering their demographic and professional characteristics, awareness, perception and implementation of the ARIA guidelines. To assess compliance with the ARIA treatment recommendations, 4 fictitious case scenarios of AR were presented, in which the respondents were asked to select the treatment of choice. <b><i>Results:</i></b> Of the 350 GPs included, only 31% were aware of the ARIA guidelines and 10% stated that they implement them. For the diagnosis of AR, 71% of the GPs ask specific IgE tests or perform skin prick tests, whereas only 29% perform an anterior rhinoscopy. ARIA users are more likely to screen for concomitant asthma. In the clinical-case section, there was a large variability in proposed therapeutic strategies. Adherence to the evidence-based ARIA treatment guidelines was low, but recent graduation was a significant predictor of compliance with these recommendations. <b><i>Conclusions:</i></b> The ARIA guidelines remain relatively unknown among Flemish GPs and even those who are aware of them still tend to treat AR independently of the guideline recommendations.
DOI: 10.6084/m9.figshare.5125756.v1
title: Supplementary Material for: Supernumerary Isochromosome 1, idic(1)(p12), Leading to Tetrasomy 1q in Burkitt Lymphoma

description: Burkitt lymphoma (BL) is an aggressive mature B-cell neoplasm. The cytogenetic hallmark are <i>MYC</i>-involving translocations, most frequently as t(8;14)(q24;q32). Additional cytogenetic abnormalities are seen in the majority of cases. The most frequent additional aberration involves the long arm of chromosome 1, either as partial or complete trisomy 1q. A very rare additional aberration is a supernumerary isochromosome 1q, i(1)(q10), resulting in tetrasomy 1q. The biological significance of this aberration is unclear. We present a highly aggressive case of BL in a child with immature B-cell immunophenotype (IP) and supernumerary i(1)(q10). Diagnostic karyotyping showed 47,XY,+i(1)(q10),t(8;14)(q24;q32)[2]/47,idem,del(15)(q24)[21]/46,XY[2]. aCGH analysis detected a gain of 1p12qter and a loss of 15q22q25. FISH analysis confirmed the isodicentric chromosome 1, which has not previously been reported in BL. In the literature, supernumerary i(1)(q10) was found in 11 cases of which &gt;80% presented with immature B-cell IP and &gt;60% relapsed or died. Tetrasomy 1q resulting from supernumerary idic(1)(p12) or i(1)(q10) is a rare genetic event in BL and probably associated with immature B-cell IP. We propose that high amplification of genes on chromosome 1p12qter may contribute to the BL IP and disease progression.
DOI: 10.6084/m9.figshare.5125762.v1
title: Supplementary Material for: Karyological Characterization of the Endemic Iberian Rock Lizard, <b><i>Iberolacerta monticola</i></b> (Squamata, Lacertidae): Insights into Sex Chromosome Evolution

description: Rock lizards of the genus <i>Iberolacerta</i> constitute a promising model to examine the process of sex chromosome evolution, as these closely related taxa exhibit remarkable diversity in the degree of sex chromosome differentiation with no clear phylogenetic segregation, ranging from cryptic to highly heteromorphic ZW chromosomes and even multiple chromosome systems (Z<sub>1</sub>Z<sub>1</sub>Z<sub>2</sub>Z<sub>2</sub>/Z<sub>1</sub>Z<sub>2</sub>W). To gain a deeper insight into the patterns of karyotype and sex chromosome evolution, we performed a cytogenetic analysis based on conventional staining, banding techniques and fluorescence in situ hybridization in the species <i>I. monticola</i>, for which previous cytogenetic investigations did not detect differentiated sex chromosomes. The karyotype is composed of 2n = 36 acrocentric chromosomes. NORs and the major ribosomal genes were located in the subtelomeric region of chromosome pair 6. Hybridization signals of the telomeric sequences (TTAGGG)<sub>n</sub> were visualized at the telomeres of all chromosomes and interstitially in 5 chromosome pairs. C-banding showed constitutive heterochromatin at the centromeres of all chromosomes, as well as clear pericentromeric and light telomeric C-bands in several chromosome pairs. These results highlight some chromosomal markers which can be useful to identify species-specific diagnostic characters, although they may not accurately reflect the phylogenetic relationships among the taxa. In addition, C-banding revealed the presence of a heteromorphic ZW sex chromosome pair, where W is smaller than Z and almost completely heterochromatic. This finding sheds light on sex chromosome evolution in the genus <i>Iberolacerta</i> and suggests that further comparative cytogenetic analyses are needed to understand the processes underlying the origin, differentiation and plasticity of sex chromosome systems in lacertid lizards.
DOI: 10.6084/m9.figshare.5125744
title: Supplementary Material for: Label-Free Quantitative Mass Spectrometry Reveals Novel Pathways Involved in LL-37 Expression

description: Antimicrobial peptides are important for a healthy host-microbe homeostasis. In infections characterized by low levels of the human cathelicidin, LL-37, induction of its expression increases clearance of pathogens. Our aim was to discover signaling pathways and compounds capable of affecting the expression of LL-37. We recently observed a synergistic induction of LL-37 expression by stimulating the colonic epithelial cell-line HT-29 with lactose and phenylbutyrate (PBA). Here, we studied regulatory circuits mediating this synergism in HT-29 cells stimulated with lactose (60 g/l) and PBA (2 mM) for 24 h by using mass spectrometry and pathway analyses. Selected pathways were evaluated for their involvement in LL-37 regulation in a <i>CAMP</i> gene-luciferase reporter system. Three pathways were examined in detail: thyroid hormone receptor and retinoid X receptor (TR/RXR) activation, eicosanoid signaling and steroid biosynthesis. Induced expression of LL-37 was observed upon stimulation with triiodothyronine (T3, 2.5 nM-1 µM for 3-30 h) and thyroxine (T4, 2.5-10 nM for 24 h). Furthermore, the synergism of lactose and PBA was reduced in cells coincubated with inhibitors of phospholipase A2, cyclooxygenase 2 or HMG-CoA reductase. Based on these results, we conclude that proteomics and pathway analyses are valuable tools for dissecting the regulatory networks involved in LL-37 expression.
DOI: 10.6084/m9.figshare.5125753.v1
title: Supplementary Material for: Dialysis Dose and Intradialytic Hypotension: Results from the HEMO Study

description: <b><i>Background:</i></b> Intradialytic hypotension (IDH) is common and is associated with increased morbidity and mortality in chronic hemodialysis patients. A higher dialysis ‘dose' may generate transient intradialytic osmotic gradients, predisposing to intracellular fluid shifts and resulting in hypotension. <b><i>Study Design:</i></b> We performed a post hoc analysis of the HEMO study, a multicenter trial that randomized chronic hemodialysis patients to high versus standard Kt/V and higher versus lower membrane flux. In order to achieve dose targets, per protocol, adjustments were made in membrane efficiency, blood flow or dialysate flow before changing session length. Detailed hemodynamic and urea kinetic modeling data were abstracted from 1,825 individuals. The primary outcome was the occurrence of hypotensive events necessitating clinical intervention (saline infusion, lowering of ultrafiltration rate or reduced blood flow). <b><i>Results:</i></b> Intradialytic hypotensive events occurred more frequently in the higher-Kt/V group (18.3 vs. 16.8%; p &lt; 0.001). Participants randomized to higher-target Kt/V had a greater adjusted risk of IDH than those randomized to standard Kt/V [odds ratio (OR) 1.12; 95% confidence interval (CI) 1.01-1.25]. Higher vs. lower dialyzer mass transfer-area coefficient for urea and rate of urea removal were associated with greater adjusted odds of IDH (OR 1.15; 95% CI 1.04-1.27 and OR 1.05; 95% CI 1.04-1.06 per mg/dl/h, respectively). <b><i>Conclusions:</i></b> Higher dialysis dose, at relatively constrained treatment times, may associate with an increased risk of IDH. These findings support the possibility that rapidity of intradialytic reductions in plasma osmolality may play an important role in mediating hemodynamic instability during dialysis.
DOI: 10.6084/m9.figshare.5125738
title: Supplementary Material for: Cariogenic Effects of Probiotic <b><i>Lactobacillus rhamnosus GG </i></b>in a Dental Biofilm Model

description: Probiotic bacteria have been suggested to inhibit <i>Streptococcus mutans </i>(SM) and thus prevent dental caries. However, supporting evidence is weak and probiotic species might be cariogenic themselves. Thus, we compared and combined the probiotic <i>Lactobacillus rhamnosus</i> GG (LGG) with SM and analysed the resulting mineral loss (ΔZ) in dental tissues<i>. </i>We simulated three biofilm compositions (SM, LGG, SM × LGG), two lesion sites (smooth enamel, dentin cavity) and two nutrition supply frequencies (twice/day, 6 times/day) in a multi-station, continuous-culture biofilm model. A total of 240 bovine enamel and dentin samples were cut, polished and embedded. All experimental procedures were performed in independent duplicates, with 10 samples being allocated to each group for each experiment (final sample size n = 20/group). Biofilms were cultured on the specimens and supplied with 2% sucrose medium and artificial saliva in consecutive pulses. After 10 days, ΔZ and bacterial numbers were assessed. SM × LGG biofilms caused significantly increased ΔZ compared with SM or LGG biofilms (p &lt; 0.01, Mann-Whitney test), and ΔZ was significantly increased in dentin cavities compared with smooth enamel lesions (p &lt; 0.01). Bacterial numbers did not significantly differ between biofilms of different species (p &gt; 0.05, ANOVA). Frequent nutrition supply significantly increased bacterial numbers (p &lt; 0.01). Biofilms in dentin cavities compared to smooth enamel harboured significantly more bacteria (p &lt; 0.05). LGG induced mineral loss especially in dentin cavities and under highly cariogenic conditions. LGG did not have inhibitory effects on SM, but rather contributed to the caries process in vitro.
DOI: 10.6084/m9.figshare.5125741
title: Supplementary Material for: Methionine Sulfoxide Reductases Protect against Oxidative Stress in <b><i>Staphylococcus aureus</i></b> Encountering Exogenous Oxidants and Human Neutrophils

description: To establish infection successfully, <i>Staphylococcus aureus</i> must evade clearance by polymorphonuclear neutrophils (PMN). We studied the expression and regulation of the methionine sulfoxide reductases (Msr) that are involved in the repair of oxidized staphylococcal proteins and investigated their influence on the fate of <i>S. aureus </i>exposed to oxidants or PMN. We evaluated a mutant deficient in <i>msrA1 </i>and <i>msrB </i>for susceptibility to hydrogen peroxide, hypochlorous acid and PMN. The expression of <i>msrA1</i> in wild-type bacteria ingested by human PMN was assessed by real-time PCR. The regulation of <i>msr </i>was studied by screening a library of two-component regulatory system (TCS) mutants for altered <i>msr</i> responses. Relative to the wild-type bacteria, bacteria deficient in Msr were more susceptible to oxidants and PMN. Upregulation of staphylococcal <i>msrA1 </i>occurred within the phagosomes of normal PMN and PMN deficient in NADPH oxidase activity. Furthermore, PMN granule-rich extract stimulated the upregulation of <i>msrA1.</i> Modulation of <i>msrA1</i> within PMN was shown to be partly dependent on the VraSR TCS. Msr contributes to staphylococcal responses to oxidative attack and PMN. Our study highlights a novel interaction between the oxidative protein repair pathway and the VraSR TCS that is involved in cell wall homeostasis.
DOI: 10.6084/m9.figshare.5125744.v1
title: Supplementary Material for: Label-Free Quantitative Mass Spectrometry Reveals Novel Pathways Involved in LL-37 Expression

description: Antimicrobial peptides are important for a healthy host-microbe homeostasis. In infections characterized by low levels of the human cathelicidin, LL-37, induction of its expression increases clearance of pathogens. Our aim was to discover signaling pathways and compounds capable of affecting the expression of LL-37. We recently observed a synergistic induction of LL-37 expression by stimulating the colonic epithelial cell-line HT-29 with lactose and phenylbutyrate (PBA). Here, we studied regulatory circuits mediating this synergism in HT-29 cells stimulated with lactose (60 g/l) and PBA (2 mM) for 24 h by using mass spectrometry and pathway analyses. Selected pathways were evaluated for their involvement in LL-37 regulation in a <i>CAMP</i> gene-luciferase reporter system. Three pathways were examined in detail: thyroid hormone receptor and retinoid X receptor (TR/RXR) activation, eicosanoid signaling and steroid biosynthesis. Induced expression of LL-37 was observed upon stimulation with triiodothyronine (T3, 2.5 nM-1 µM for 3-30 h) and thyroxine (T4, 2.5-10 nM for 24 h). Furthermore, the synergism of lactose and PBA was reduced in cells coincubated with inhibitors of phospholipase A2, cyclooxygenase 2 or HMG-CoA reductase. Based on these results, we conclude that proteomics and pathway analyses are valuable tools for dissecting the regulatory networks involved in LL-37 expression.
DOI: 10.6084/m9.figshare.5125747
title: Supplementary Material for: The Human IgE Repertoire

description: IgE is a key mediator in allergic diseases. However, in strong contrast to other antibody isotypes, many details of the composition of the human IgE repertoire are poorly defined. The low levels of human IgE in the circulation and the rarity of IgE-producing B cells are important reasons for this lack of knowledge. In this review, we summarize the current knowledge on these repertoires both in terms of their complexity and activity, i.e. knowledge which despite the difficulties encountered when studying the molecular details of human IgE has been acquired in recent years. We also take a look at likely future developments, for instance through improvements in sequencing technology and methodology that allow the isolation of additional allergen-specific human antibodies mimicking IgE, as this certainly will support our understanding of human IgE in the context of human disease in the years to come.
DOI: 10.6084/m9.figshare.5125735
title: Supplementary Material for: Distinct Signaling Cascades of TREM-1, TLR and NLR in Neutrophils and Monocytic Cells

description: Triggering receptor expressed on myeloid cells 1 (TREM-1) is an important mediator of innate inflammatory responses in microbial infections and sepsis. TREM-1 ligation on neutrophils (PMN) or monocytes results in the production of proinflammatory cytokines. Engagement of TREM-1 induces the activation of MAP kinases as well as rapid Ca<sup>2+</sup> mobilization. However, a detailed understanding of TREM-1 signaling pathways is currently lacking. We evaluated the TREM-1 signaling hierarchy in monocytic cells and found that the acute myeloid leukemia cell line MUTZ-3 expresses TREM-1 in a natural and functional manner. We compared essential signaling molecules of the TREM-1, TLR and NLR cascade in MUTZ-3 cells as well as primary monocytes or PMN by Western blot analysis. These studies confirmed the essential role of phosphatidyl inositide 3-kinase (PI3K) and p38MAPK in the TREM-1 as well as the TLR or NLR cascade of monocytic cells. Importantly, PI3K and p38MAPK signals in monocytic cells both control Ca<sup>2+</sup> mobilization and are directly connected in the TREM-1 signaling hierarchy, which contrasts previous results obtained in PMN. Taken together, our results indicate cell type-specific differences in the TREM-1 signaling cascade and contribute to an enhanced understanding of the regulation of innate inflammatory responses.
DOI: 10.6084/m9.figshare.5125738.v1
title: Supplementary Material for: Cariogenic Effects of Probiotic <b><i>Lactobacillus rhamnosus GG </i></b>in a Dental Biofilm Model

description: Probiotic bacteria have been suggested to inhibit <i>Streptococcus mutans </i>(SM) and thus prevent dental caries. However, supporting evidence is weak and probiotic species might be cariogenic themselves. Thus, we compared and combined the probiotic <i>Lactobacillus rhamnosus</i> GG (LGG) with SM and analysed the resulting mineral loss (ΔZ) in dental tissues<i>. </i>We simulated three biofilm compositions (SM, LGG, SM × LGG), two lesion sites (smooth enamel, dentin cavity) and two nutrition supply frequencies (twice/day, 6 times/day) in a multi-station, continuous-culture biofilm model. A total of 240 bovine enamel and dentin samples were cut, polished and embedded. All experimental procedures were performed in independent duplicates, with 10 samples being allocated to each group for each experiment (final sample size n = 20/group). Biofilms were cultured on the specimens and supplied with 2% sucrose medium and artificial saliva in consecutive pulses. After 10 days, ΔZ and bacterial numbers were assessed. SM × LGG biofilms caused significantly increased ΔZ compared with SM or LGG biofilms (p &lt; 0.01, Mann-Whitney test), and ΔZ was significantly increased in dentin cavities compared with smooth enamel lesions (p &lt; 0.01). Bacterial numbers did not significantly differ between biofilms of different species (p &gt; 0.05, ANOVA). Frequent nutrition supply significantly increased bacterial numbers (p &lt; 0.01). Biofilms in dentin cavities compared to smooth enamel harboured significantly more bacteria (p &lt; 0.05). LGG induced mineral loss especially in dentin cavities and under highly cariogenic conditions. LGG did not have inhibitory effects on SM, but rather contributed to the caries process in vitro.