bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microsatellite Instability assessment in Black South African Colorectal Cancer patients reveal an increased incidence of suspected Lynch syndrome
Authors: McCabe M. , Perner Y. , Magobo R. , Magangane P. , Mirza S. , Penny C. 
Published: October 2019

AbstractMicrosatellite Instability (MSI) is a hallmark of colorectal cancer (CRC) and occurs in 15–16% of CRC. Molecular biological information of CRC in South Africa (SA) is largely unrecorded. This study was undertaken to determine the frequency of MSI, with particular reference to Lynch syndrome (LS) with a view to improve surveillance and prevention strategies. This was a retrospective study on CRC samples diagnosed between 2011–2015 at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Samples diagnosed between 2011–2012 were screened for MSI by PCR and mismatch repair (MMR) immunohistochemistry (IHC), and additional BRAFV600E mutational analysis performed. T-tests, Fischer’s exact and Chi square statistical tests were applied. Twelve percent of patients displayed MSI, with increased frequency in black (15%) versus other ethnic group (OEG) (8%) patients. MSI patients were significantly younger than microsatellite stable (MSS) patients, however when stratified by ethnicity, black patients were predominantly younger (median age: 47), with increased MSH2/6 loss, and no BRAF mutations. These findings suggest a large proportion of young black SA CRC patients develop via the LS pathway due to earlier age onset and predominant MSH2/6 protein loss. SA patients of other ethnicities appear to follow the more well established sporadic MSI pathway.
Insights into replicative senescence of human testicular peritubular cells
Authors: Schmid Nina , Flenkenthaler Florian , Stöckl Jan B. , Dietrich Kim-Gwendolyn , Köhn Frank M. , Schwarzer J. Ullrich , Kunz Lars , Luckner Manja , Wanner Gerhard , Arnold Georg J. , Fröhlich Thomas , Mayerhofer Artur 
Published: October 2019

AbstractThere is evidence for an age-related decline in male reproductive functions, yet how the human testis may age is not understood. Human testicular peritubular cells (HTPCs) transport sperm, contribute to the spermatogonial stem cell (SSC) niche and immune surveillance, and can be isolated and studied in vitro. Consequences of replicative senescence of HTPCs were evaluated to gain partial insights into human testicular aging. To this end, early and advanced HTPC passages, in which replicative senescence was indicated by increased cell size, altered nuclear morphology, enhanced β-galactosidase activity, telomere attrition and reduced mitochondrial DNA (mtDNA), were compared. These alterations are typical for senescent cells, in general. To examine HTPC-specific changes, focused ion beam scanning electron microscopy (FIB/SEM) tomography was employed, which revealed a reduced mitochondrial network and an increased lysosome population. The results coincide with the data of a parallel proteomic analysis and indicate deranged proteostasis. The mRNA levels of typical contractility markers and growth factors, important for the SSC niche, were not significantly altered. A secretome analysis identified, however, elevated levels of macrophage migration inhibitory factor (MIF) and dipeptidyl peptidase 4 (DPP4), which may play a role in spermatogenesis. Testicular DPP4 may further represent a possible drug target.
Species-specific and collection method-dependent differences in endometrial susceptibility to seminal plasma-induced RNA degradation
Authors: Fernandez-Fuertes Beatriz , Sánchez José María , Bagés-Arnal Sandra , McDonald Michael , Yeste Marc , Lonergan Pat 
Published: October 2019

AbstractThis study aimed to determine the effect of bull seminal plasma (SP) and sperm on endometrial function. Bovine endometrial explants were incubated with: ejaculated sperm with or without SP, epididymal sperm, or SP alone. Neither ejaculated nor epididymal sperm induced differential expression ofIL1A, IL1B, IL6, IL8, PTGES2, TNFA, andLIF. Interestingly, SP had a detrimental effect on endometrial RNA integrity. Addition of an RNase inactivation reagent to SP blocked this effect, evidencing a role for a SP-RNase. Because bulls deposit the ejaculate in the vagina, we hypothesized that the bovine endometrium is more sensitive to SP-RNase than vaginal and cervical tissues (which come into contact with SP during mating), or to endometrium from intrauterine ejaculators (such as the horse). In addition, due to differences in SP-RNase abundance depending on SP collection method (i.e., with an artificial vagina, AV, or by electroejaculation, EE), this effect was also tested. Bull SP, collected by AV, degrades RNA of mare endometrium, and bovine vagina, cervix and endometrium. However, stallion SP or bull SP collected by EE did not elicit this effect. Thus, results do not support a role for SP in modulating endometrial function to establish pregnancy in cattle.
Loss of the dermis zinc transporter ZIP13 promotes the mildness of fibrosarcoma by inhibiting autophagy
Authors: Lee Mi-Gi , Choi Min-Ah , Chae Sehyun , Kang Mi-Ae , Jo Hantae , Baek Jin-myoung , In Kyu-Ree , Park Hyein , Heo Hyojin , Jang Dongmin , Brito Sofia , Kim Sung Tae , Kim Dae-Ok , Lee Jong-Soo , Kim Jae-Ryong , Bin Bum-Ho 
Published: October 2019

AbstractFibrosarcoma is a skin tumor that is frequently observed in humans, dogs, and cats. Despite unsightly appearance, studies on fibrosarcoma have not significantly progressed, due to a relatively mild tumor severity and a lower incidence than that of other epithelial tumors. Here, we focused on the role of a recently-found dermis zinc transporter, ZIP13, in fibrosarcoma progression. We generated two transformed cell lines from wild-type and ZIP13-KO mice-derived dermal fibroblasts by stably expressing the Simian Virus (SV) 40-T antigen. The ZIP13−/− cell line exhibited an impairment in autophagy, followed by hypersensitivity to nutrient deficiency. The autophagy impairment in the ZIP13−/− cell line was due to the low expression of LC3 gene and protein, and was restored by the DNA demethylating agent, 5-aza-2’-deoxycytidine (5-aza) treatment. Moreover, the DNA methyltransferase activity was significantly increased in the ZIP13−/− cell line, indicating the disturbance of epigenetic regulations. Autophagy inhibitors effectively inhibited the growth of fibrosarcoma with relatively minor damages to normal cells in xenograft assay. Our data show that proper control over autophagy and zinc homeostasis could allow for the development of a new therapeutic strategy to treat fibrosarcoma.
The quick Sepsis-related Organ Failure Assessment (qSOFA) is a good predictor of in-hospital mortality in very elderly patients with bloodstream infections: A retrospective observational study
Authors: Ramos-Rincón José M. , Fernández-Gil Adela , Merino Esperanza , Boix Vicente , Gimeno Adelina , Rodríguez-Diaz Juan C. , Valero Beatriz , Sánchez-Martínez Rosario , Portilla Joaquín 
Published: October 2019

AbstractPeople over 80 years old are now the fastest-growing age group. Bloodstream infections (BSI) in these patients may present with specific characteristics. The objective of this study was to analyze independent factors affecting in-hospital mortality (IHM) due to BSI in very elderly patients (≥80 years of age) and to compare the clinical presentation of BSI in patients aged 80–89 years versus those aged 90 or more. Retrospective, cross-sectional and observational study of BSI in patients aged 80 years or older. The study used IHM as the primary outcome. Stepwise multiple logistic regression models were used to identify associations between potential predictors and IHM. Of the 336 included patients, 76.8% (n = 258) were in the 80–89-year age group and 23.2% (n = 78) in the 90+ age group; 17.3% (n = 58) of patients died during admission. This outcome was independently associated with quick Sepsis Related Organ Failure Assessment (qSOFA) of 2 or more (adjusted odds ratio [aOR] 4.7, 95% confidence interval [CI] 2.3–9.4; p < 0.001). Other predictors included an origin of BSI outside the urinary tract (aOR 5.5, 95% CI 2.4–12.6; p < 0.001), thrombocytopenia (aOR 4.9, 95% CI 1.8–13.4; p = 0.002), hospital-acquired infection (aOR 3.0, 95% CI 1.2–7.5; p = 0.015), and inappropriate empiric antibiotics (aOR 2.0, 95% CI 1.1–3.9; p = 0.04). IHM was 23.1% in the 90+ age group and 15.5% in patients aged 80 to 89 (p = 0.012). However, the 90+ age group was more likely to have a score of at least 2 on the qSOFA (29.9% vs. 19.1%, p = 0.043) and Pitt bacteremia scales (44.9% vs. 30.2%; p = 0.02), as well as chronic kidney disease (56.4% vs. 36.0%; p = 0.001) and altered mental state (40.3% vs. 25.7%; p = 0.013). In conclusion: A qSOFA score of 2 or more and a BSI originating outside the urinary tract were independent predictors of IHM. The 90+ age group was at higher risk than the 80–89-year age group of having a qSOFA score and Pitt bacteremia score of 2 or more as well as an altered mental state.
The effect of lattice disorder on the low-temperature heat capacity of (U1−yThy)O2 and 238Pu-doped UO2
Authors: Vălu Sorin-Octavian , De Bona Emanuele , Popa Karin , Griveau Jean-Christophe , Colineau Eric , Konings Rudy J. M. 
Published: October 2019

AbstractThe low-temperature heat capacity of (U1−yThy)O2 and 238Pu-doped UO2 samples were determined using hybrid adiabatic relaxation calorimetry. Results of the investigated systems revealed the presence of the magnetic transition specific for UO2 in all three intermediate compositions of the uranium-thorium dioxide (y = 0.05, 0.09 and 0.12) and in the 238Pu-doped UO2 around 25 K. The magnetic behaviour of UO2 exposed to the high alpha dose from the 238Pu isotope was studied over time and it was found that 1.6% 238Pu affects the magnetic transition substantially, even after short period of time after annealing. In both systems the antiferromagnetic transition changes intensity, shape and Néel temperature with increasing Th-content and radiation dose, respectively, related to the increasing disorder on the crystal lattice resulting from substitution and defect creation.
Losartan does not inhibit cigarette smoke-induced lung inflammation in mice
Authors: Hepworth M. L. , Passey S. L. , Seow H. J. , Vlahos R. 
Published: October 2019

AbstractChronic Obstructive Pulmonary Disease (COPD) is a progressive lung disease largely caused by cigarette smoking (CS) and is characterized by lung inflammation and airflow limitation that is not fully reversible. Approximately 50% of people with COPD die of a cardiovascular comorbidity and current pharmacological strategies provide little benefit. Therefore, drugs that target the lung and the cardiovascular system concurrently may be an advantageous therapeutic strategy. The aim of this study was to see whether losartan, an angiotensin-II AT1a receptor antagonist widely used to treat hypertension associated with cardiovascular disease, protects against CS-induced lung inflammation in mice. Male BALB/c mice were exposed to CS for 8 weeks and treated with either losartan (30 mg/kg) or vehicle daily. Mice were euthanized and bronchoalveolar lavage fluid (BALF) inflammation, and whole lung cytokine, chemokine and protease mRNA expression assessed. CS caused significant increases in BALF total cells, macrophages, neutrophils and whole lung IL-6, TNF-α, CXCL-1, IL-17A and MMP12 mRNA expression compared to sham-exposed mice. However, losartan only reduced CS-induced increases in IL-6 mRNA expression. Angiotensin-II receptor expression was reduced in lung tissue from CS-exposed mice. In conclusion, losartan did not inhibit CS-induced BALF cellularity despite reducing whole lung IL-6 mRNA and Ang-II receptor expression.
Impact of Early Life Antibiotic Exposure and Neonatal Hyperoxia on the Murine Microbiome and Lung Injury
Authors: Althouse Melissa H. , Stewart Christopher , Jiang Weiwu , Moorthy Bhagavatula , Lingappan Krithika 
Published: October 2019

AbstractCross talk between the intestinal microbiome and the lung and its role in lung health remains unknown. Perinatal exposure to antibiotics disrupts the neonatal microbiome and may have an impact on the preterm lung. We hypothesized that perinatal antibiotic exposure leads to long-term intestinal dysbiosis and increased alveolar simplification in a murine hyperoxia model. Pregnant C57BL/6 wild type dams and neonatal mice were treated with antibiotics before and/or immediately after delivery. Control mice received phosphate-buffered saline (PBS). Neonatal mice were exposed to 95% oxygen for 4 days or room air. Microbiome analysis was performed using 16S rRNA gene sequencing. Pulmonary alveolarization and vascularization were analyzed at postnatal day (PND) 21. Perinatal antibiotic exposure modified intestinal beta diversity but not alpha diversity in neonatal mice. Neonatal hyperoxia exposure altered intestinal beta diversity and relative abundance of commensal bacteria in antibiotic treated mice. Hyperoxia disrupted pulmonary alveolarization and vascularization at PND 21; however, there were no differences in the degree of lung injury in antibiotic treated mice compared to vehicle treated controls. Our study suggests that exposure to both hyperoxia and antibiotics early in life may cause long-term alterations in the intestinal microbiome, but intestinal dysbiosis may not significantly influence neonatal hyperoxic lung injury.
A micropatterned substrate for on-surface enzymatic labelling of linearized long DNA molecules
Authors: Varapula Dharma , LaBouff Eric , Raseley Kaitlin , Uppuluri Lahari , Ehrlich Garth D. , Noh Moses , Xiao Ming 
Published: October 2019

AbstractOptical mapping of linearized DNA molecules is a promising new technology for sequence assembly and scaffolding, large structural variant detection, and diagnostics. This is currently achieved either using nanochannel confinement or by stretching single DNA molecules on a solid surface. While the first method necessitates DNA labelling before linearization, the latter allows for modification post-linearization, thereby affording increased process flexibility. Each method is constrained by various physical and chemical limitations. One of the most common techniques for linearization of DNA uses a hydrophobic surface and a receding meniscus, termed molecular combing. Here, we report the development of a microfabricated surface that can not only comb the DNA molecules efficiently but also provides for sequence-specific enzymatic fluorescent DNA labelling. By modifying a glass surface with two contrasting functionalities, such that DNA binds selectively to one of the two regions, we can control DNA extension, which is known to be critical for sequence-recognition by an enzyme. Moreover, the surface modification provides enzymatic access to the DNA backbone, as well as minimizing non-specific fluorescent dye adsorption. These enhancements make the designed surface suitable for large-scale and high-resolution single DNA molecule studies.
Thiotrophic bacterial symbiont induces polyphenism in giant ciliate host Zoothamnium niveum
Authors: Bright Monika , Espada-Hinojosa Salvador , Volland Jean-Marie , Drexel Judith , Kesting Julia , Kolar Ingrid , Morchner Denny , Nussbaumer Andrea , Ott Jörg , Scharhauser Florian , Schuster Lukas , Zambalos Helena Constance , Nemeschkal Hans Leo 
Published: October 2019

AbstractEvolutionary theory predicts potential shifts between cooperative and uncooperative behaviour under fluctuating environmental conditions. This leads to unstable benefits to the partners and restricts the evolution of dependence. High dependence is usually found in those hosts in which vertically transmitted symbionts provide nutrients reliably. Here we study host dependence in the marine, giant colonial ciliate Zoothamnium niveum and its vertically transmitted, nutritional, thiotrophic symbiont from an unstable environment of degrading wood. Previously, we have shown that sulphidic conditions lead to high host fitness and oxic conditions to low fitness, but the fate of the symbiont has not been studied. We combine several experimental approaches to provide evidence for a sulphide-tolerant host with striking polyphenism involving two discrete morphs, a symbiotic and an aposymbiotic one. The two differ significantly in colony growth form and fitness. This polyphenism is triggered by chemical conditions and elicited by the symbiont’s presence on the dispersing swarmer. We provide evidence of a single aposymbiotic morph found in nature. We propose that despite a high fitness loss when aposymbiotic, the ciliate has retained a facultative life style and may use the option to live without its symbiont to overcome spatial and temporal shortage of sulphide in nature.
Local redox conditions in cells imaged via non-fluorescent transient states of NAD(P)H
Authors: Tornmalm Johan , Sandberg Elin , Rabasovic Mihailo , Widengren Jerker 
Published: October 2019

AbstractThe autofluorescent coenzyme nicotinamide adenine dinucleotide (NADH) and its phosphorylated form (NADPH) are major determinants of cellular redox balance. Both their fluorescence intensities and lifetimes are extensively used as label-free readouts in cellular metabolic imaging studies. Here, we introduce fluorescence blinking of NAD(P)H, as an additional, orthogonal readout in such studies. Blinking of fluorophores and their underlying dark state transitions are specifically sensitive to redox conditions and oxygenation, parameters of particular relevance in cellular metabolic studies. We show that such dark state transitions in NAD(P)H can be quantified via the average fluorescence intensity recorded upon modulated one-photon excitation, so-called transient state (TRAST) monitoring. Thereby, transitions in NAD(P)H, previously only accessible from elaborate spectroscopic cuvette measurements, can be imaged at subcellular resolution in live cells. We then demonstrate that these transitions can be imaged with a standard laser-scanning confocal microscope and two-photon excitation, in parallel with regular fluorescence lifetime imaging (FLIM). TRAST imaging of NAD(P)H was found to provide additional, orthogonal information to FLIM and allows altered oxidative environments in cells treated with a mitochondrial un-coupler or cyanide to be clearly distinguished. We propose TRAST imaging as a straightforward and widely applicable modality, extending the range of information obtainable from cellular metabolic imaging of NAD(P)H fluorescence.
New Method for Evaluating Surface Roughness Parameters Acquired by Laser Scanning
Authors: Tonietto Leandro , Gonzaga Luiz , Veronez Mauricio Roberto , Kazmierczak Claudio de Souza , Arnold Daiana Cristina Metz , Costa Cristiano André da 
Published: October 2019

AbstractQuality evaluation of a material’s surface is performed through roughness analysis of surface samples. Several techniques have been presented to achieve this goal, including geometrical analysis and surface roughness analysis. Geometric analysis allows a visual and subjective evaluation of roughness (a qualitative assessment), whereas computation of the roughness parameters is a quantitative assessment and allows a standardized analysis of the surfaces. In civil engineering, the process is performed with mechanical profilometer equipment (2D) without adequate accuracy and laser profilometer (3D) with no consensus on how to interpret the result quantitatively. This work proposes a new method to evaluate surface roughness, starting from the generation of a visual surface roughness signature, which is calculated through the roughness parameters computed in hierarchically organized regions. The evaluation tools presented in this new method provide a local and more accurate evaluation of the computed coefficients. In the tests performed it was possible to quantitatively analyze roughness differences between ceramic blocks and to find that a quantitative microscale analysis allows to identify the largest variation of roughness parameters Raavg, Rasdv, Ramin and Ramax between samples, which benefit the evaluation and comparison of the sampled surfaces.
Prematurely ruptured dominant follicles often retain competent oocytes in infertile women
Authors: Teramoto S. , Osada H. , Shozu M. 
Published: October 2019

AbstractOvulation consists of a follicle’s rupture and subsequent oocyte extrusion, although there is a paucity of evidence regarding whether every follicle’s rupture is associated with extrusion of its oocyte. We examined this issue in a large-scale window-of-opportunity study by attempting aspiration of single dominant follicles that were found to have ruptured before a scheduled oocyte retrieval during in vitro fertilisation and embryo transfer treatment of infertile women. We were able to aspirate 587 of 1,071 ultrasonographically confirmed post-rupture dominant follicles from 1,071 women (i.e. one dominant follicle per woman) and retrieved 225 oocytes (oocyte recovery ratio: 43.4% of aspirated follicles), which yielded 28 live births (live birth ratio: 11.0% of retrieved oocytes). Interestingly, the live birth ratio for post-rupture dominant follicles was not statistically different from that achieved using regular pre-rupture aspiration of dominant follicles (1,085/8,977, 12.1%). These findings suggest that oocyte extrusion frequently does not occur after follicle rupture in infertile women undergoing in vitro fertilisation treatment, although the oocyte retained in the follicle can remain competent for use during that treatment.
Depletion of CD11c+ dendritic cells in apolipoprotein E-deficient mice limits angiotensin II-induced abdominal aortic aneurysm formation and growth
Authors: Krishna Smriti M. , Moran Corey S. , Jose Roby J. , Lazzaroni Sharon , Huynh Pacific , Golledge Jonathan 
Published: October 2019

AbstractObjective: The role of chronic inflammation in abdominal aortic aneurysm (AAA) is controversial. CD11c+ antigen-presenting cells (APCs) (dendritic cells (DCs)) have been reported in human AAA samples but their role is unclear. The effect of conditional depletion of CD11c+ cells on experimental AAA was investigated in the angiotensin II (AngII)-infused apolipoprotein E-deficient (ApoE–/–) mouse model.Approach: CD11c-diphtheria toxin (DT or D.tox) receptor (DTR), ovalbumin (OVA) fragment aa 140–386, and enhanced green fluorescent protein (eGFP)-ApoE–/– (CD11c.DOG.ApoE–/–) mice were generated and CD11c+ cell depletion achieved with D.tox injections (8 ng/g body weight, i.p., every-other-day). AAA formation and growth were assessed by measurement of supra-renal aortic (SRA) diameter in vivo by serial ultrasound and by morphometry assessment of harvested aortas at the end of the study.Results: Depletion of CD11c+ cells by administration of D.tox on alternative days was shown to reduce the maximum diameter of AAAs induced by 28 days AngII infusion compared with controls (D.tox, 1.58 ± 0.03 mm vs Vehicle control, 1.81 ± 0.06 mm, P&lt;0.001). CD11c+ depletion commencing after AAA establishment by 14 days of AngII infusion, was also shown to lead to smaller AAAs than controls after a further 14 days (D.tox, 1.54 ± 0.04 mm vs Vehicle control, 1.80 ± 0.03 mm, P&lt;0.001). Flow cytometry revealed significantly lower numbers of circulating CD44hi CD62Llo effector CD4 T cells, CD44hi CD62Llo effector CD8 T cells and B220+ B cells in CD11c+ cell-depleted mice versus controls. CD11c+ depletion attenuated SRA matrix degradation indicated by decreased neutrophil elastase activity (P=0.014), lower elastin degradation score (P=0.012) and higher collagen content (P=0.002).Conclusion: CD11c+ cell-depletion inhibited experimental AAA development and growth associated with down-regulation of circulating effector T cells and attenuated matrix degradation. The findings suggest involvement of autoreactive immune cells in AAA pathogenesis.