Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterisation of the effect of oxygen tension on response of fetal rabbit ductus arteriosus to vasodilators.

OBJECTIVE The aims of the study were (1) to elucidate the effects of raised oxygen tension on the response of the ductus arteriosus to a range of vasodilators; and (2) to establish the effect, if any, of cyclo-oxygenase inhibition on the interaction between oxygen and prostaglandin (PG)E2. METHODS Rings of ductus arteriosus were isolated from fetal New Zealand White rabbits at 28 d gestation (term = 31) and precontracted with 10 microM noradrenaline in the presence of the cyclo-oxygenase inhibitor indomethacin (1 microM). Cumulative relaxation response curves were obtained from a range of vasodilators and their pEC50 (-log10 of the interpolated molar concentration causing 50% of the maximum response) and maximum relaxant response (MRR) were determined in 15% oxygen (neonatal oxygen tension, 13-14.3 kPa) and 2% oxygen (fetal oxygen tension, 2.5-3.0 kPa). In addition, the effects of (1) omitting indomethacin and (2) its substitution by 1 microM flubriprofen were studied on the interaction between oxygen and PGE2. RESULTS In 1 microM indomethacin, nifedipine and atrial natriuretic peptide had no effect on ductal tone in either oxygen tension. In 15% oxygen, the rank order of MRR was forskolin > cicaprost > PGE2 >> cromakalim >> sodium nitroprusside approximately adenosine approximately 0. The MRR of all agonists was increased in 2% oxygen except forskolin which caused complete relaxation in 15% oxygen. In 15% oxygen, the rank order of pEC50 was PGE2 >> cicaprost approximately cromakalim approximately forskolin. PGE2 was 70.8 times more potent than cicaprost. The pEC50 of all four agonists was increased in 2% oxygen. The increase in pEC50 could not be explained by a decreased extent of precontraction. The MRR to PGE2 in 15% oxygen and the magnitude of the increase in pEC50 to PGE2 going from 15% to 2% oxygen were the same in 1 microM flubriprofen, 1 microM indomethacin, or in the absence of these drugs. However, in 2% oxygen, the MRR to PGE2 was increased in 1 microM indomethacin or 1 microM flubriprofen compared with control. CONCLUSIONS (1) Increasing oxygen tension from fetal to neonatal levels desensitises the ductus arteriosus to a range of vasodilators. (2) There is evidence that prostacyclin has a physiological role in the control of the rabbit ductus arteriosus. (3) The effect of oxygen on the potency of PGE2 is independent of cyclo-oxygenase products, whereas its effect on the efficacy of PGE2 is modulated by an endogenous cyclo-oxygenase product.
Lignin‐modifying enzymes in filamentous basidiomycetes – ecological, functional and phylogenetic review

Filamentous fungi owe powerful abilities for decomposition of the extensive plant material, lignocellulose, and thereby are indispensable for the Earth's carbon cycle, generation of soil humic matter and formation of soil fine structure. The filamentous wood‐decaying fungi belong to the phyla Basidiomycota and Ascomycota, and are unique organisms specified to degradation of the xylem cell wall components (cellulose, hemicelluloses, lignins and extractives). The basidiomycetous wood‐decaying fungi form brackets, caps or resupinaceous (corticioid) fruiting bodies when growing on wood for dissemination of their sexual basidiospores. In particular, the ability to decompose the aromatic lignin polymers in wood is mostly restricted to the white rot basidiomycetes. The white‐rot decay of wood is possible due to secretion of organic acids, secondary metabolites, and oxidoreductive metalloenzymes, heme peroxidases and laccases, encoded by divergent gene families in these fungi. The brown rot basidiomycetes obviously depend more on a non‐enzymatic strategy for decomposition of wood cellulose and modification of lignin. This review gives a current ecological, genomic, and protein functional and phylogenetic perspective of the wood and lignocellulose‐decaying basidiomycetous fungi. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Investigation of acute nanoparticulate aluminum toxicity in zebrafish

In freshwater fish, aluminum is a well‐recognized gill toxicant, although responses are influenced by pH. Aluminum nanomaterials are being used in diverse applications that are likely to lead to environmental release and exposure. However, it is unclear if the effects of nanoparticulate aluminum are similar to those of other forms of aluminum or require special consideration. To examine the acute toxicological effects of exposure to aluminum nanoparticle (Al‐NP)s, adult female zebrafish were exposed to either Al‐NPs or aluminum chloride for up to 48 hours in moderately hard fresh water. Al‐NPs introduced into test water rapidly aggregated and up to 80% sedimented from the water column during exposures. No mortality was caused by concentrations of Al‐NP up to 12.5 mg/L. After exposure, tissue concentrations of aluminum, effects on gill morphology, Na+, K+ ‐ATPase (NKA) activity, and global gene expression patterns were examined. Exposure to both aluminum chloride and nanoparticulate aluminum resulted in a concentration dependent decrease in sodium potassium ATPase activity, although Al‐NP exposure did not alter gill morphology as measured by filament widths. Decreased ATPase activity coincided with decreases in filamental NKA staining and mucous cell counts. Analysis of gill transcriptional responses demonstrated that exposure to 5 mg/L Al‐NP only resulted in significant changes in expression of two genes, whereas aluminum chloride exposure significantly affected the expression of 105 genes. Taken together, these results indicate that nanoparticulate aluminum has little acute toxicity for zebrafish in moderately hard freshwater. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2010.
The Jun Kinase/Stress-activated Protein Kinase Pathway Functions to Regulate DNA Repair and Inhibition of the Pathway Sensitizes Tumor Cells to Cisplatin*

We have studied the role of Jun/stress-activated protein kinase (JNK/SAPK) pathway in DNA repair and cisplatin resistance in T98G glioblastoma cells. JUN/SAPK is activated by DNA damage and phosphorylates serines 63 and 73 in the N-terminal domain of c-Jun, which is known to increase its transactivation properties. We show that treatment of T98G glioblastoma cells with cisplatin but not the transplatin isomer activates JNK/SAPK about 10-fold. T98G cells, which are highly resistent to cisplatin (IC50 = 140 ± 13 μm), modified to express a nonphosphorylatable dominant negative c-Jun (termed dnJun) exhibit decreased viability following treatment with cisplatin, but not transplatin, in proportion (r Pearson = 0.98) to the level of dnJun expressed leading to a 7-fold decreased IC50. Similar effects are observed in U87 cells, PC-3 cells, and MCF-7 cells, as well as in T98G cells modified to express TAM-67, a known inhibitor of c-Jun function. In contrast, no sensitization effect was observed in cells modified to express wild-type c-Jun. Furthermore, through quantitative polymerase chain reaction-stop assays, we show that dnJun expressing cells were inhibited in repair of cisplatin adducts (p = 0.55), whereas repair is readily detectable (p = 0.003) in parental cells. These observations indicate that the JNK/SAPK pathway is activated by cisplatin-induced DNA damage and that this response is required for DNA repair and viability following cisplatin treatment. Regulation of DNA repair following genotoxic stress may be a normal physiological role of the JNK/SAPK pathway.
Clinical characteristics and outcome of southern Chinese males with systemic lupus erythematosus

The aims were to study the gender differences in clinical manifestations, disease course and organ damage in systemic lupus erythematosus (SLE). Clinical manifestations, autoantibody profile, relapses and damage scores were obtained from 51 Chinese males with SLE and compared with 201 consecutive female SLE controls. Fifty-one males were identified among 630 SLE patients who attended our clinics, giving a male prevalence of 8% and a female to male ratio of 11.4–1. Both the male SLE patients and the female controls had similar age and SLEDAI score at disease onset. Male SLE patients had less alopecia (P = 0.03), Raynaud's phenomenon (P = 0.01) and anti-Ro (P = 0.049) during the course of the disease but none of the differences were statistically significant after correction for multiple observations. The prevalence of major organ involvement in either sex was not different. Both groups of patients had a comparable mean duration of follow-up (104 vs 102 months, P = 0.87). Males had a significantly lower rate of relapses (total No. of flares/patient-year: 0.23 in men vs 0.33 in women, P = 0.04), but the frequency of severe flares (No. of severe flares/patient/year in men 0.08 vs 0.12 in women, P = 0.16) was not significantly different from the females. Male patients with positive anti-Ro had significantly less overall flares than their female counterparts who were anti-Ro positive (0.16 vs 0.34, P = 0.006). However, the use of immunosuppressive agents for disease control in patients of both sexes was similar. 22 (43%) of the males and 78 (39%) of the females had organ damage. A higher percentage of male patients had impairment of renal function (P = 0.006) but the proportion of patients who required dialysis was not different (4% in men vs 2% in females, P = 0.92). There was also a trend of more cardiovascular damage in the males but the difference was not statistically significant (P = 0.09). The mean SLICC/ACR scores were not significantly higher in the males than the females (0.71 vs 0.60, P ‘ 0.47). Males tend to differ from females in clinical manifestations, immunological profile and disease course in SLE. However, there was no gender difference in the involvement of major organs/systems. Males had less overall disease flares than the females but the rate of severe flares was not significantly lower. For patients who were anti-Ro positive, males had significantly less total number of flares/patient-year than their female counterparts. More renal impairment and cardiovascular damage was present in our male lupus patients but the overall damage scores were not significantly higher.
The influence of positive and negative emotional associations on semantic processing in depression: An fMRI study

In depression, patients suffer from emotional and cognitive deficits, among others in semantic processing. If these semantic deficits are cognitive or interact with emotional dysfunctions, is still an open question. The aim of the current study was to investigate the influence of emotional valence on the neural correlates of semantic priming in major depression. In a lexical decision task, positive, negative, and neutral word pairs were presented during fMRI measurement. Nineteen inpatients and 19 demographically matched controls were recruited. Behaviorally, positive and neutral valence induced a priming effect whereas negative valence induced no effect (controls) or even inhibition (slower RT for related stimuli) in patients. At the neural level, the semantic relation effect revealed similar neural activation in right middle frontal regions for patients and controls. Group differences emerged in the right fusiform gyrus and the ACC. Activity associated with positive valence differed at the DLPFC and amygdala and for negative valence at putamen and cerebellum. The activation of amygdala and DLPFC correlated negatively with the severity of depression. To conclude, semantic processing deficits in depression are modulated by emotional valence of the stimulus on the behavioral as well as on neural level in right‐lateralized prefrontal areas and the amygdala. The results highlighted an influence of depression severity on emotion information processing as the severity of symptoms correlated negatively with neural responses to positively and negatively valenced information. Hence, the dysfunctional emotion processing may further enhance the cognitive deficits in depression. Hum Brain Mapp 35:471–482, 2014. © 2012 Wiley Periodicals, Inc.
VITRIFICATION OF IN VIVO AND IN VITRO PRODUCED OVINE BLASTOCYSTS

Although cryopreservation of bovine embryo has made great progress in recent years, little achievement was obtained in ovine embryo freezing, especially in vitro produced embryos. However, a simple and efficient method for cryopreservation of sheep embryos will be important for application of ovine embryonic techniques such as in vitro fertilization, transgenic, cloning and etc. In this study ovine blastocysts, produced in vivo or in vitro, were cryopreserved by vitrification in EFS40 (40% ethylene glycol (EG), 18% ficoll and 0.5 M sucrose) or GFS40 (40% glycerol (GL), 18% ficoll and 0.5 Mol sucrose). In Vitro produced, early blastocysts were directly plunged into liquid nitrogen (LN2) after preparation by one of the following procedures at 25°C: (A) equilibration in EFS40 for 1 min; (B) equilibration in EFS40 for 2 min; (C) equilibration in EFS40 for 30 s following pretreatment in 10% EG for 5 min; (D) equilibration in EFS40 for 30s following pretreatment in EFS20 for 2 min (E) equilibration in GFS30 for 30 s following pretreatment in 10% GL for 5 min. The survival rates observed after thawing and in vitro culture for 12 h were A 78.0% (39/50), B 50.0% (26/52), C 93.3% (70/75), D 92.0% (46/50) and E 68.0% (34/50). Survival rates were not significantly different for treatments C and D (p>0.05), but those for groups C and D were significantly higher than for A, B and E (p<0.05). After 24 h in vitro culture, hatched blastocyst rates were A 28.0% (14/50), B 21.1% (11/52), C 49.3% (37/75), D 48.0% (24/50), E 32.0% (16/50) and control 54.0% (27/50). The hatching rates for groups A, B and E were significantly lower than the control (p<0.05) in which early IVF blastocysts were cultured in fresh SOFaaBSA medium following treatment in PBS containing 0.3% BSA for 30 min, but for groups C and D it was similar to the control (p>0.05). The freezing procedures A, B and C were used to vitrify in vivo produced, early blastocysts recovered from superovulated ewes. The survival rates of frozen-thawed in vivo embryos were A 94.7% (72/76), B 75.0% (45/60) and C 96.4% (54/56) and for group B was significantly lower than for the other two treatment groups (p<0.05). Hatched blastocyst rates were A 46.0% (35/76), B 26.6% (16/60), C 51.8% (29/56) and the control 56.7% (34/60) in which early blastocysts from superovulation were cultured in fresh SOFaaBSA medium following treatment in PBS containing 0.3% BSA for 30 min. The hatching rate for treatment B was significantly lower than for the control (p<0.05) but did not differ between groups A, C and the control (p>0.05). Frozen-thawed embryos vitrified by procedure C were transferred into synchronous recipient ewes. Pregnancy and lambing rates were similar for embryos transferred fresh or frozen/thawed for both in vivo and in vitro produced embryos. These rates did not differ between in vivo and in vitro embryos transferred fresh (p>0.05). However, for frozen-thawed embryos, both rates were significantly lower for in vitro than for in vivo produced embryos (p<0.05).
A Brain Electrical Activity Electroencephalographic-Based Biomarker of Functional Impairment in Traumatic Brain Injury: A Multi-Site Validation Trial.

The potential clinical utility of a novel quantitative electroencephalographic (EEG)-based Brain Function Index (BFI) as a measure of the presence and severity of functional brain injury was studied as part of an independent prospective validation trial. The BFI was derived using quantitative EEG (QEEG) features associated with functional brain impairment reflecting current consensus on the physiology of concussive injury. Seven hundred and twenty adult patients (18-85 years of age) evaluated within 72 h of sustaining a closed head injury were enrolled at 11 U.S. emergency departments (EDs). Glasgow Coma Scale (GCS) score was 15 in 97%. Standard clinical evaluations were conducted and 5 to 10 min of EEG acquired from frontal locations. Clinical utility of the BFI was assessed for raw scores and percentile values. A multinomial logistic regression analysis demonstrated that the odds ratios (computed against controls) of the mild and moderate functionally impaired groups were significantly different from the odds ratio of the computed tomography (CT) postive (CT+, structural injury visible on CT) group (p = 0.0009 and p = 0.0026, respectively). However, no significant differences were observed between the odds ratios of the mild and moderately functionally impaired groups. Analysis of variance (ANOVA) demonstrated significant differences in BFI among normal (16.8%), mild TBI (mTBI)/concussed with mild or moderate functional impairment, (61.3%), and CT+ (21.9%) patients (p < 0.0001). Regression slopes of the odds ratios for likelihood of group membership suggest a relationship between the BFI and severity of impairment. Findings support the BFI as a quantitative marker of brain function impairment, which scaled with severity of functional impairment in mTBI patients. When integrated into the clinical assessment, the BFI has the potential to aid in early diagnosis and thereby potential to impact the sequelae of TBI by providing an objective marker that is available at the point of care, hand-held, non-invasive, and rapid to obtain.
Distinct proteomic features of two fibrogenic liver cell populations: Hepatic stellate cells and portal myofibroblasts

In chronic liver diseases, the accumulation of extracellular matrix leading to fibrosis is caused by myofibroblasts, the origins of which are debatable. We performed a comparative proteomic study to identify markers and gain insight into distinct functions of myofibroblasts derived either from hepatic stellate cells (HSCs) or from portal mesenchymal cells. After isolation from normal liver and culture in similar conditions, myofibroblastic HSCs (MF‐HSCs) presented enlarged cytoplasms whereas portal myofibroblasts (PMFs) were more proliferative, and formed more stress fibers. The two cell types were subjected to comparative analyses by 2‐D MS/MS. Six proteins were overexpressed in PMFs, with myofibroblast‐related typical functions. Among them, cofilin‐1 showed the greatest difference in expression and a lower pI than expected. Immunoblot demonstrated higher levels of phosphorylation, a modification of the protein implicated in stress fiber formation. Eleven proteins, mostly involved in stress response, were overexpressed in MF‐HSCs. Cytoglobin had the highest level of overexpression, as confirmed by reverse transcription quantitative real‐time PCR, immunoblot and immunocytochemical analyses. These results identify cytoglobin as the best marker for distinguishing MF‐HSCs from PMFs and suggest different functions for the two cell populations in the liver wound healing response, with a prominent role for PMFs in scar formation.
Scalar coupling and zero‐quantum coherence relaxation in STEAM: Implications for spectral editing of lactate

Accurate values were obtained for the lactate zero‐quantum coherence frequency, ωZQ = ωi‐ωs = CH3–CH chemical shift difference, and scalar coupling constant, J, by using the methyl signal's amplitude modulation during the TM period of a STEAM sequence, 90°–TE/2–90°–TM–90°–TE/2‐ Acquire. Although most previous work has used J= 7.35 Hz, or 1/J= 136 ms, the actual value is J= 6.93 ± 0.05 Hz or 1/J = 144.3 ± 1 ms. In addition, the CH3–CH chemical shift difference = 2.7956 ± 0.0005 ppm, and the relaxation time for zero‐quantum coherence, TZQ, was much shorter than either T2 or T1 for the methyl resonance. A small component of the signal with TE= 144 ms, which was not modulated at the zero‐quantum coherence frequency or by scalar coupling, was assigned to longitudinal two‐spin order magnetization (IzSz) created by imperfect radio frequency pulse profiles. This information will allow improved editing of the lactate signal and more accurate quantitation of lactate concentrations.
Targetable activating mutations are very frequent in GCB and ABC diffuse large B‐cell lymphoma

Diffuse large B cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy that can be divided in two major subgroups, germinal center B‐cell‐like (GCB) and activated B‐cell‐like (ABC). Activating mutations of genes involved in the BCR and NF‐κB pathways (CD79A, CD79B, MYD88, and CARD11) or in epigenetic regulation (EZH2) have been recently reported, preferentially in one of the two DLBCL subtypes. We analyzed the mutational status of these five recurrently mutated genes in a cohort of 161 untreated de novo DLBCL. Overall, 93 mutations were detected, in 61 (38%) of the patients. The L265P MYD88 mutation was the most frequent MYD88 variant (n = 18), observed exclusively in the ABC subtype. CD79A/CD79B ITAM domains were targeted in ABC DLBCL (12/77; 16%), whereas CARD11 mutations were equally distributed in the two subtypes. The EZH2 Y641 substitution was found almost exclusively in the GCB subgroup (15/62; 24%). Twenty cases (12%) displayed two activating mutations, including the most frequent CD79/MYD88 variants combination (n = 8) which is observed exclusively in the ABC subtype. When considering only ABC DLBCL patients treated by rituximab plus chemotherapy, the presence of an activating NF‐κB mutation was associated with an unfavorable outcome (3‐years OS 26% for mutated cases versus 67% for the cases without mutations, P = 0.0337). Our study demonstrates that activating and targetable mutations are observed at a very high frequency in DLBCL at the time of diagnosis, indicating that sequencing of a limited number of genes could help tailor an optimal treatment strategy in DLBCL. © 2013 Wiley Periodicals, Inc.
Inuit women's attitudes and experiences towards cervical cancer and prevention strategies in Nunavik, Quebec

Objectives: To describe the attitudes about and experiences with cervical cancer, Pap smear screenings and the HPV vaccine among a sample of Inuit women from Nunavik, Quebec, Canada. We also evaluated demographic and social predictors of maternal interest in HPV vaccination. Study design: A mixed method design was used with a cross-sectional survey and focus group interviews. Methods: Women were recruited through convenience sampling at 2 recruitment sites in Nunavik from March 2008 to June 2009. Differences in women's responses by age, education, and marital status were assessed. Unconditional logistic regression was used to determine predictors of women's interest in HPV vaccination for their children. Results: Questionnaires were completed by 175 women aged 18–63, and of these women a total of 6 women aged 31–55 participated in 2 focus groups. Almost half the survey participants had heard of cervical cancer. Women often reported feelings of embarrassment and pain during the Pap smear and older women were more likely to feel embarrassed than younger women. Only 27% of women had heard of the HPV vaccine, and 72% of these women were interested in vaccinating their child for HPV. No statistically significant predictors of maternal interest in HPV vaccination were found. Conclusions: Our findings indicate that health service planners and providers in Nunavik should be aware of potential barriers to Pap smear attendance, especially in the older age groups. Given the low awareness of cervical cancer, the Pap smear and the HPV vaccine, education on cervical cancer and prevention strategies may be beneficial. 1Published ‘ahead-of-print’ 26 October 2011 (at www.ijch.fi) in accordance with previous publisher's routines.