Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct neuropsychological profiles correspond to distribution of cortical thinning in inherited prion disease caused by insertional mutation

Background The human prion diseases are a group of universally fatal neurodegenerative disorders associated with the auto-catalytic misfolding of the normal cell surface prion protein (PrP). Mutations causative of inherited human prion disease (IPD) include an insertion of six additional octapeptide repeats (6-OPRI) and a missense mutation (P102L) with large families segregating for each mutation residing in southern England. Here we report for the first time the neuropsychological and clinical assessments in these two groups. Method The cognitive profiles addressing all major domains were obtained for 26 patients (18 6-OPRI, 8 P102L) and the cortical thickness determined using 1.5T MRI in a subset of 10 (six 6-OPRI, four P102L). Results The cognitive profiles were different in patients with the two mutations in the symptomatic phase of the disease. The 6-OPRI group had lower premorbid optimal levels of functioning (assessed on the NART) than the P102L group. In the symptomatic phase of the disease the 6-OPRI patients had significantly more executive dysfunction than the P102L group and were more impaired on tests of perception and nominal functions. There was anecdotal evidence of low premorbid social performance in the 6-OPRI but not P102L patients. Cortical thinning distribution correlated with the neuropsychological profile in the 6-OPRI group principally involving the parietal, occipital and posterior frontal regions. The small number of patients in the P102L group precluded statistical comparison between the groups. Conclusions The 6-OPRI patients had more widespread and severe cognitive dysfunction than the P102L group and this correlated with cortical thinning distribution.
Plasma proteins as potential targets of abnormal Savda syndrome in asthma patients treated with unique Uighur prescription

The therapeutic effect of Uighur prescription on abnormal Savda in asthma patients was evaluated using plasma proteomics in order to elucidate the biological mechanism and identify potential therapeutic targets of abnormal Savda. In the present study, 40 asthma patients with abnormal Savda including abnormal Savda Munziq and Savda Mushil were enrolled and treated with Uighur prescription. The effect of Uighur prescription on protein expression and potential targets was investigated by isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics and bioinformatics analysis. Expression of candidate proteins was verified by an enzyme-linked immunosorbent assay. Following treatment with the Uighur prescription, 22 proteins were differentially expressed in the plasma of patients with asthma and abnormal Savda. The majority of these proteins were localized in intermediate filaments and the cytoskeleton and acted as antioxidant enzymes and binding proteins. Furthermore, they participated in the defense and inflammatory response, and the response to oxidative stress and wound healing. Peroxiredoxin 2 and carboxypeptidase B2 expression was significantly upregulated, whereas S100A7 was considerably downregulated in the whole plasma of patients (all P<0.05) in accordance with the iTRAQ proteomics data. Uighur prescription of abnormal Savda may affect the whole regulatory network of protein expression that is altered following the development of abnormal Savda in patients with asthma.
Effect of micro-alga supplementation on goat and cow milk fatty acid composition

The microalgae cultivation has been developed over the last decades because it is capable of producing valuable metabolites, such as n-3 fatty acids for nutraceutical purposes. Aim of this study was to investigate the effect of the micro-alga as fat supplement on fatty acid profile of goat and cow milk, with particular reference to n-3 fatty acids and rumenic acid. Twenty dairy goats and 16 dairy cows were randomly allocated to two isonitrogenous treatment groups to investigate the effect of micro-alga supplementation on the composition and fatty acid profile of milk. The 1st goat group was fed with alfalfa hay and concentrate; the 2nd goat group received the same forages but the concentrate was supplemented with 10 g kg-1 DM intake micro-alga. The control group cows were fed with alfalfa hay, corn silage and concentrate, while the experimental animals were fed with the same forages but the concentrate was supplemented with 7.4 g kg-1 DM intake micro-alga. The experimental periods lasted for 17 d. The micro-alga supplements considerably increased rumenic acid concentration in milk (1.20% vi. 1.54%, P < 0.001 for goats; 0.75% vs. 0.85%, P < 0.05 for cows). The n-3 fatty acids were higher in milk (1.02 vs. 1.35; P < 0.001 for goats; 0.47 vs. 0.56; P < 0.05 for cows) and in addition the n-6/n-3 ratio was also more favorable in the micro-alga supplemented groups (3.53 vs. 2.88; P < 0.01 for goats; 4.18 vs. 3.36; P < 0.05 for cows). It is concluded that the diet with micro-alga supplementation significantly increased the concentration of beneficial fatty acids in both goat and cow milk.
Effects of an anti-VEGF-A monoclonal antibody on laser-induced choroidal neovascularization in mice: optimizing methods to quantify vascular changes.

PURPOSE The purpose of this study was to evaluate different methods of detecting and quantifying experimentally induced choroidal neovascularization (CNV) and vascular changes induced on CNV by an anti-VEGF-A monoclonal antibody. METHODS Choroidal neovascularization was induced by 532-nm diode laser in C57BL/6 mice. Ten days after the laser, the following methods were used to detect the new vessels: high-resolution angiography with fluorescein isothiocyanate-dextran; immunohistochemistry with biotinylated isolectin, rabbit anti-NG2, rat anti-CD31, rabbit anti-VWF, rat ani-CD105, rabbit anti-collagen IV, rat anti-ICAM-2, rabbit anti-desmin, and rat anti-MECA 32; and intravital injection of fluorescein-labeled Lycopersicon esculentum (tomato) lectin. To verify the validity of these staining methods in the quantification of treated CNV, the authors applied the most effective of these techniques to three groups of mice after laser induction of CNV and treatment with an anti-VEGF full antibody (G6-31). RESULTS Fluorescein isothiocyanate-dextran angiography, rat anti-ICAM-2 immunostaining, and tomato lectin intravital injection resulted in the most effective means of identifying choroidal neovascularization. A certain amount of nonspecific fluorescence was detected in the area of CNV for each METHOD This fluorescence appeared more intense when fluorescein isothiocyanate-dextran was used. Tomato lectin injection and rat anti-ICAM-2 immunostaining were the methods that better recorded the antiangiogenic drug effect. CONCLUSIONS Because of easy execution, low background fluorescence, and detailed visualization of new vessels, intravital injection of tomato lectin followed by a quantification based on threshold fluorescence represents the best technique for measuring CNV and the vascular changes induced by anti-VEGF-A monoclonal antibody in mice.
The Origin of Man : A Chromosomal Pictorial Legacy

AMan, gorilla, and chimpanzee likely shared an ancestor in whom thefine genetic organization of chromosomes was similar to that of present man. A comparative analysis of high-resolution chromosomes from orangutan, gorilla, chimpanzee, and man suggests that 18 of23 pairs of chromosomes of modern man are virtually identical to those ofour "common hominoid ancestor," with the remaining pairs slightly different. From this lineage, gorilla separated first, and three major chromosomal rearrangements presumably occurred in a progenitor of chimpanzee and man before the final divergence of these two species. A precursor of the hominoid ancestor and orangutan is also assumed. 1525 o n S ep te m be r 4, 2 01 4 w w w . s ci en ce m ag . o rg D ow nl oa de d fr om o n S ep te m be r 4, 2 01 4 w w w . s ci en ce m ag . o rg D ow nl oa de d fr om o n S ep te m be r 4, 2 01 4 w w w . s ci en ce m ag . o rg D ow nl oa de d fr om o n S ep te m be r 4, 2 01 4 w w w . s ci en ce m ag . o rg D ow nl oa de d fr om o n S ep te m be r 4, 2 01 4 w w w . s ci en ce m ag . o rg D ow nl oa de d fr om o n S ep te m be r 4, 2 01 4 w w w . s ci en ce m ag . o rg D ow nl oa de d fr om 11 (9 I~~~~~~~~~~~~~~~~~~~~~~~~~91 1 2 3 4 5
Impact of Host Developmental Age on the Transcriptome of the Symbiotic Bacterium Buchnera aphidicola in the Pea Aphid (Acyrthosiphon pisum)

ABSTRACT Of the 617 genes from Buchnera aphidicola, the obligate bacterial symbiont of the pea aphid, 23% were differentially expressed in embryos compared to adults. Genes involved in flagellar apparatus and riboflavin synthesis exhibited particularly robust upregulation in embryos, suggesting functional differences between the symbiosis in the adult and embryo insect.
Infestation of the Copepod Acartia tonsa with the Stalked Ciliate Zoothamnium

An entire population of the copepod Acartia tonsa in the Patuxent River, Maryland, was infested with a stalked protozoan of the genus Zoothamnium. Each copepod had 25 to 200 ciliates attached around the appendages. The infestation occurred at the time when Acartia tonsa was being replaced as the dominant copepod by Acartia clausi.
Isentropic equation of state of 2-flavor QCD

Using Taylor expansions of the pressure obtained previously in studies of 2-flavor QCD at nonzero chemical potential we calculate expansion coefficients for the energy and entropy densities up to $\mathcal{O}({\ensuremath{\mu}}_{q}^{6})$ in the quark chemical potential. We use these series in ${\ensuremath{\mu}}_{q}/T$ to determine lines of constant entropy per baryon number ($S/{N}_{B}$) that characterize the expansion of dense matter created in heavy ion collisions. In the high temperature regime these lines are found to be well approximated by lines of constant ${\ensuremath{\mu}}_{q}/T$. In the low temperature phase, however, the quark chemical potential is found to increase with decreasing temperature. This is in accordance with resonance gas model calculations. Along the lines of constant $S/{N}_{B}$ we calculate the energy density and pressure. Within the accuracy of our present analysis we find that the ratio $p/ϵ$ for $Tg{T}_{0}$ as well as the softest point of the equation of state, $(p/ϵ{)}_{\mathrm{min}}\ensuremath{\simeq}0.075$, show no significant dependence on $S/{N}_{B}$.
Role of Dendritic Dopamine of the Substantia Nigra in the Modulation of Nigrocollicular γ‐Aminobutyric Acid Release: In Vivo Studies in the Rat

The release of γ‐[3H]aminobutyric acid ([3H]GABA) newly synthesized from [3H]glutamine was estimated in the superior colliculus of ketamine‐anesthetized rats superfused via a push‐pull cannula. A significant amount of [3H]GABA was spontaneously released in the superior colliculus (582 ± 49 pCi/10 min). A major part of the large K+‐evoked increase of the [3H]GABA release was Ca2+ dependent. When neuronal activity of the substantia nigra was enhanced by nigral application of K+ (30 mM) or bicuculline (10–4M), a persistent increase of the collicular [3H]GABA release was observed (60 and 80%, respectively). Conversely, when nigral activity was reduced by nigral application of GABA (10–4M) or superfusion with a Ca2+ free medium, a sustained decrease of the collicular [3H]GABA release was observed (‐30 and ‐40%. respectively). Following the nigral application of a selective D2‐receptor agonist, RU 24926 (10–5M), for 30 min in 6‐hydroxydopamine‐lesioned rats, a phasic increase (60%) of the collicular [3H]GABA release was detected. This effect could result from an activation of nigrocollicular GABAergic neurons by D2‐receptor stimulation, because nigral activity and collicular release of [3H]GABA changed in a parallel direction.
Pathophysiology of the Lower Urinary Tract: Continence and Incontinence

Introduction To better understand the pathophysiologic mechanisms occurring in incontinence, we begin with a brief review of the normal mechanisms of continence. We subsequently review how incontinence can occur when these systems do not function normally. Both anatomic and neurologic hypotheses for the causes of stress urinary incontinence (SUI) are discussed. Pathophysiology of overactive detrusor is discussed in terms of its neurogenic and non-neurogenic causes. The chapter finishes with a review of the relationship between urinary symptoms and pelvic organ prolapse. Normal Mechanisms of Continence In the normal adult, urinary control can be subdivided into a bladder filling and urine storage phase, and a bladder emptying and voiding phase. Therefore, normal lower urinary tract function requires the ability to store urine at low pressure while the detrusor muscle is quiescent, as well as the ability to completely empty the bladder voluntarily with low resistance urine passage. The bladder and urethra are the most important structures for proper storage and emptying. Other important components include pelvic floor musculature, ligaments, and neural control. Anatomy has been discussed in previous sections and bladder filling, emptying, and neural control has been discussed in previous sections and therefore these topics will not be reviewed here. Correspondence: Margot S. Damaser, PhD, Research Biomedical Engineer and Associate Professor, Research Service (151), Hines VA Hospital, 5 Avenue and Roosevelt Road, Hines, IL, 60141. E-mail: margot.Damaser@ med.va. gov CLINICAL OBSTETRICS AND GYNECOLOGY Volume 47, Number 1, 28–35 © 2004, Lippincott Williams & Wilkins, Inc.
Novel metal-matrix composites with integrally-bound nanoscale carbon

Abstract : We characterized the chemical, thermophysical, and mechanical properties of nanomaterials with up to 5 wt% nanocarbon (aka covetics) in aluminum and copper metals. The nanocarbon is detectable by EDS and XPS but not by analytical methods such as LECO and GDMS. Nanocarbon raises the melting point and significantly alters surface tension, and thus porosity, during solidification. Open questions remain about the observation of higher density than would be predicted by the rule of mixtures. In aluminum alloys, we observed an increase in as-rolled strength and hardness with increasing amounts of nanocarbon. In copper, thermal conductivity was anisotropic: up to 50% higher in the extrusion direction and at least 25% lower in the transverse direction,and was different between transient and steady state test conditions. In aluminum, we observed a significant increase in electrical conductivity with nanocarbon, from 47 to 67% IACS. These materials are commercially promising because they are produced by conversion of inexpensive carbon powder to nanocarbon in the melt? paving the way for the production of nanomaterials in pyrometallurgical operations with economies of scale.
Quinacrine Overcomes Resistance to Erlotinib by Inhibiting FACT, NF-κB, and Cell-Cycle Progression in Non–Small Cell Lung Cancer

Erlotinib is a tyrosine kinase inhibitor approved for the treatment of patients with advanced non–small cell lung cancer (NSCLC). In these patients, erlotinib prolongs survival but its benefit remains modest because many tumors express wild-type (wt) EGFR or develop a second-site EGFR mutation. To test drug combinations that could improve the efficacy of erlotinib, we combined erlotinib with quinacrine, which inhibits the FACT (facilitates chromatin transcription) complex that is required for NF-κB transcriptional activity. In A549 (wtEGFR), H1975 (EGFR-L858R/T790M), and H1993 (MET amplification) NSCLC cells, this drug combination was highly synergistic, as quantified by Chou–Talalay combination indices, and slowed xenograft tumor growth. At a sub-IC50 but more clinically attainable concentration of erlotinib, quinacrine, alone or in combination with erlotinib, significantly inhibited colony formation and induced cell-cycle arrest and apoptosis. Quinacrine decreased the level of active FACT subunit SSRP1 and suppressed NF-κB–dependent luciferase activity. Knockdown of SSRP1 decreased cell growth and sensitized cells to erlotinib. Moreover, transcriptomic profiling showed that quinacrine or combination treatment significantly affected cell-cycle–related genes that contain binding sites for transcription factors that regulate SSRP1 target genes. As potential biomarkers of drug combination efficacy, we identified genes that were more strongly suppressed by the combination than by single treatment, and whose increased expression predicted poorer survival in patients with lung adenocarcinoma. This preclinical study shows that quinacrine overcomes erlotinib resistance by inhibiting FACT and cell-cycle progression, and supports a clinical trial testing erlotinib alone versus this combination in advanced NSCLC. Mol Cancer Ther; 13(9); 2203–14. ©2014 AACR.
Strategic and sporadic marine consumption at the onset of the Neolithic: increasing temporal resolution in the isotope evidence

Stable isotope analysis has provided crucial new insights into dietary change at the Neolithic transition in north-west Europe, indicating an unexpectedly sudden and radical shift from marine to terrestrial resources in coastal and island locations. Investigations of early Neolithic skeletal material from Sumburgh on Shetland, at the far-flung margins of the Neolithic world, suggest that this general pattern may mask significant subtle detail. Analysis of juvenile dentine reveals the consumption of marine foods on an occasional basis. This suggests that marine foods may have been consumed as a crucial supplementary resource in times of famine, when the newly introduced cereal crops failed to cope with the demanding climate of Shetland. This isotopic evidence is consistent with the presence of marine food debris in contemporary middens. The occasional and contingent nature of marine food consumption underlines how, even on Shetland, the shift from marine to terrestrial diet was a key element in the Neolithic transition.
Myocardial Effects of Desflurane in Hamsters with Hypertrophic Cardiomyopathy

Background The effects of desflurane on myocardial contraction and relaxation in diseased myocardium have not been completely understood. Methods The effects of desflurane (1.8 to 9.4 vol%) in left ventricular papillary muscles of healthy hamsters and those with genetically induced cardiomyopathy (strain BIO 14.6) were investigated in vitro (29 [degree sign]C, pH 7.40, Ca2+ 2.5 mM; stimulation frequency, 3/min) under low (isotony) and high (isometry) load. Data are mean percentages of baseline +/− SD. Results Desflurane induced no significant inotropic effect in healthy muscles (maximum unloaded shortening velocity and isometric active force at 9.4 vol%: 97 +/− 9% and 92 +/− 20%, respectively). In contrast, in cardiomyopathic muscles, desflurane induced a moderate negative inotropic effect (maximum unloaded shortening velocity and active force at 9.4 vol%: 84 +/− 19% and 75 +/− 25%, respectively). The negative inotropic effect was more pronounced than that in healthy muscles under low (P < 0.05) but not high load, and even when concentrations were corrected for minimum alveolar concentrations in each strain. Adrenoceptor blockade or pretreatment with reserpine did not modify the inotropic effect of desflurane, suggesting the absence of intramyocardial catecholamine release. However, tyramine also did not induce any significant catecholamine release in hamster myocardium. In both strains, desflurane induced no significant lusitropic effect under low or high load. Conclusions Desflurane had no inotropic effect in healthy muscles and a moderate negative inotropic effect in cardiomyopathic muscles. The absence of desflurane‐induced intramyocardial catecholamine release was related to hamster myocardium characteristics.
University of Dundee Modelling and investigation of the CD 4 + T cells-macrophages paradox in melanoma

It is generally accepted that tumour cells can be eliminated by M1 anti-tumour macrophages and CD8+ T cells. However, experimental results over the past 10–15 years have shown that B16 mouse melanoma cells can be eliminated by the CD4+ T cells alone (either Th1 or Th2 sub-types), in the absence of CD8+ T cells. In some studies, elimination of B16 melanoma was associated with a Th1 immune response (i.e., elimination occurred in the presence of cytokines produced by Th1 cells), while in other studies melanoma elimination was associated with a Th2 immune response (i.e., elimination occurred in the presence of cytokines produced by Th2 cells). Moreover, macrophages have been shown to be present inside the tumours, during both Th1 and Th2 immune responses. To investigate the possible biological mechanisms behind these apparently contradictory results, we develop a class of mathematical models for the dynamics of Th1 and Th2 cells, and M1 and M2 macrophages in the presence/absence of tumour cells. Using this mathematical model, we show that depending on the repolarisation rates between M1 and M2 macrophages, we obtain tumour elimination in the presence of a type-I immune response (i.e., more Th1 and M1 cells, compared to the Th2 and M2 cells), or in the presence of a typeII immune response (i.e., more Th2 and M2 cells). Moreover, tumour elimination is also possible in the presence of a mixed type-I/type-II immune response. Tumour growth always occurs in the presence of a type-II immune response, as observed experimentally. Finally, tumour dormancy is the result of a delicate balance between the pro-tumour effects of M2 cells and the anti-tumour effects of M1 and Th1 cells.
Homozygous mutation of P450 side-chain cleavage enzyme gene (CYP11A1) in 46, XY patient with adrenal insufficiency, complete sex reversal, and agenesis of corpus callosum.

CONTEXT The cholesterol side-chain cleavage enzyme catalyzes the conversion of cholesterol to pregnanalone in the first step of steroidogenic pathways. Defective enzyme activity leads to the deficiency of all steroid hormones, including progesterone, which is essential to sustain term pregnancy. RESULTS We report a homozygous point mutation in the CYP11A1 gene in a 46, XY phenotypic female born at term to healthy heterozygous parents, presenting relatively late at the age of 1 yr 9 months with life-threatening adrenal insufficiency and complete sex reversal. She was found to have complete agenesis of corpus callosum. The mutation resulted in a single amino acid substitution: valine for alanine at position 359. The functional analysis of the mutant enzyme revealed markedly reduced enzyme activity, but about 11% residual activity was demonstrated. We explained the completion of pregnancy to term and the late presentation by a possible difference in the mutant enzyme activity in vivo and in vitro or by the residual mutant activity, which would have been enough to maintain pregnancy and viability of the patient. The clinical findings of nearly undetectable levels of steroid hormones at presentation are explained by the total disruption of steroidogenic cells later on, with recurrent ACTH stimulation leading to intramitochondrial cholesterol accumulation and cell death (a two-hit mechanism). CONCLUSION This report of a homozygous mutation in CYP11A1 gene in a child with agenesis of corpus callosum shows that homozygous mutations in CYP11A1 gene can be compatible with term pregnancy and delayed presentation.