Miracle-dz/UniFAR-FTUs huggingface dataset:
A Neuronal Activity-Dependent Dual Function Chromatin-Modifying Complex Regulates Arc Expression1,2,3

The regulation of neuronal gene expression requires dynamic changes in chromatin structure as evidenced by the fact that dysregulation of the enzymes responsible for chromatin modification often leads to intellectual disability. In this article, we characterize a chromatin-modifying complex containing the X-linked mental retardation-associated protein PHF8 and the Alzheimer’s disease-associated protein TIP60, which regulates the expression of an important neuronal activity-dependent gene, Arc. Abstract Chromatin modification is an important epigenetic mechanism underlying neuroplasticity. Histone methylation and acetylation have both been shown to modulate gene expression, but the machinery responsible for mediating these changes in neurons has remained elusive. Here we identify a chromatin-modifying complex containing the histone demethylase PHF8 and the acetyltransferase TIP60 as a key regulator of the activity-induced expression of Arc, an important mediator of synaptic plasticity. Clinically, mutations in PHF8 cause X-linked mental retardation while TIP60 has been implicated in the pathogenesis of Alzheimer’s disease. Within minutes of increased synaptic activity, this dual function complex is rapidly recruited to the Arc promoter, where it specifically counteracts the transcriptionally repressive histone mark H3K9me2 to facilitate the formation of the transcriptionally permissive H3K9acS10P, thereby favoring transcriptional activation. Consequently, gain-of-function of the PHF8−TIP60 complex in primary rat hippocampal neurons has a positive effect on early activity-induced Arc gene expression, whereas interfering with the function of this complex abrogates it. A global proteomics screen revealed that the majority of common interactors of PHF8 and TIP60 were involved in mRNA processing, including PSF, an important molecule involved in neuronal gene regulation. Finally, we proceeded to show, using super-resolution microscopy, that PHF8 and TIP60 interact at the single molecule level with PSF, thereby situating this chromatin modifying complex at the crossroads of transcriptional activation. These findings point toward a mechanism by which an epigenetic pathway can regulate neuronal activity-dependent gene transcription, which has implications in the development of novel therapeutics for disorders of learning and memory.
Repeat Gamma Knife surgery for recurrent trigeminal neuralgia: long-term outcomes and systematic review.

OBJECT The purpose of this study was to establish the safety and efficacy of repeat Gamma Knife surgery (GKS) for recurrent trigeminal neuralgia (TN). METHODS Using the prospective database of TN patients treated with GKS in Timone University Hospital (Marseille, France), data were analyzed for 737 patients undergoing GKS for TN Type 1 from July 1992 to November 2010. Among the 497 patients with initial pain cessation, 34.4% (157/456 with ≥ 1-year follow-up) experienced at least 1 recurrence. Thirteen patients (1.8%) were considered for a second GKS, proposed only if the patients had good and prolonged initial pain cessation after the first GKS, with no other treatment alternative at the moment of recurrence. As for the first GKS, a single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 4-14 mm) anterior to the emergence of the nerve (retrogasserian target). A median maximum dose of 90 Gy (range 70-90 Gy) was delivered. Data for 9 patients with at least 1-year followup were analyzed. A systematic review of literature was also performed, and results are compared with those of the Marseille study. RESULTS The median time to retreatment in the Marseille study was 72 months (range 12-125 months) and in the literature it was 17 months (range 3-146 months). In the Marseille study, the median follow-up period was 33.9 months (range 12-96 months), and 8 of 9 patients (88.9%) had initial pain cessation with a median of 6.5 days (range 1-180 days). The actuarial rate for new hypesthesia was 33.3% at 6 months and 50% at 1 year, which remained stable for 7 years. The actuarial probabilities of maintaining pain relief without medication at 6 months and 1 year were 100% and 75%, respectively, and remained stable for 7 years. The systematic review analyzed 20 peer-reviewed studies reporting outcomes for repeat GKS for recurrent TN, with a total of 626 patients. Both the selection of the cases for retreatment and the way of reporting outcomes vary widely among studies, with a median rate for initial pain cessation of 88% (range 60%-100%) and for new hypesthesia of 33% (range 11%-80%). CONCLUSIONS Results from the Marseille study raise the question of surgical alternatives after failed GKS for TN. The rates of initial pain cessation and recurrence seem comparable to, or even better than, those of the first GKS, according to different studies, but toxicity is much higher, both in the Marseille study and in the published data. Neither the Marseille study data nor literature data answer the 3 cardinal questions regarding repeat radiosurgery in recurrent TN: which patients to retreat, which target is optimal, and which dose to use.
Pandemic (H1N1) 2009 Influenza Virus Seroconversion Rates in HIV-Infected Individuals

The impact of pandemic (H1N1) 2009 influenza in HIV-infected individuals is unknown. Determining the prevalence of pandemic influenza in this at-risk group will guide vaccination programs. After the first pandemic wave, the seroprevalence rate of pandemic influenza in HIV-infected individuals in western Sydney, New South Wales, Australia, was 34.2%, similar to the rate observed in the general population. However, true seroprevalence is more accurately determined by seroconversion, defined as a 4-fold or greater rise between preexposure and postexposure antibody levels, which was 14.6% in the present study. Seroconversion rates were independent of CD4+ T-lymphocyte count and HIV plasma load. Neither HIV infection, nor severe immunosuppression, was a significant risk factor for pandemic influenza during the first southern hemisphere pandemic wave.
A computationally efficient optimisation-based method for parameter identification of kinematically determinate and over-determinate biomechanical systems

This paper introduces a general optimisation-based method for identification of biomechanically relevant parameters in kinematically determinate and over-determinate systems from a given motion. The method is designed to find a set of parameters that is constant over the time frame of interest as well as the time-varying system coordinates, and it is particularly relevant for biomechanical motion analysis where the system parameters can be difficult to accurately determine by direct measurements. Although the parameter identification problem results in a large-scale optimisation problem, we show that, due to a special structure in the linearised Karush–Kuhn–Tucker optimality conditions, the solution can be found very efficiently. The method is applied to a set of test problems relevant for gait analysis. These involve determining the local coordinates of markers placed on the model, segment lengths and joint axes of rotation from both gait and range of motion experiments.
Detection of Genital HPV Types in Fingertip Samples from Newly Sexually Active Female University Students

Background: Little is known about detection of genital human papilloma virus (HPV) types in women's fingertips. The study objectives were to determine the presence of genital HPV types in fingertip samples and the agreement between fingertip and genital samples for detecting HPV. Methods: At triannual visits, genital and fingertip samples were collected from female university students and tested for 37 HPV genotypes by PCR-based assay. Type-specific concordance between paired fingertip and genital samples was evaluated using κ statistics for percent positive agreement (κ+). Paired samples with type-specific concordant fingertip and genital results were selected for variant characterization. Results: A total of 357 fingertip samples were collected from 128 women. HPV prevalence in fingertip samples was 14.3%. Although percent positive agreement between fingertips and genitals for detecting type-specific HPV was low (17.8%; κ+ = 0.17; 95% confidence interval, 0.10-0.25), 60.4% of type-specific HPV detected in the fingertips was detected in a concurrent genital sample. All but one of 28 paired concordant samples were positive for the same type-specific variant in the fingertip and genital sample. Redetection of HPV types at the subsequent visit was more common in genital samples (73.3%) than in fingertip samples (14.5%; P < 0.001). Conclusions: Detection of genital HPV types in the fingertips was not uncommon. Although impossible to distinguish between deposition of DNA from the genitals to the fingertips and true fingertip infection, the rarity of repeat detection in the fingertips suggests that deposition is more common. Impact: Finger-genital transmission is plausible but unlikely to be a significant source of genital HPV infection. Cancer Epidemiol Biomarkers Prev; 19(7); 1682–5. ©2010 AACR.
The relationship between the age of onset of musical training and rhythm synchronization performance: validation of sensitive period effects

A sensitive period associated with musical training has been proposed, suggesting the influence of musical training on the brain and behavior is strongest during the early years of childhood. Experiments from our laboratory have directly tested the sensitive period hypothesis for musical training by comparing musicians who began their training prior to age seven with those who began their training after age seven, while matching the two groups in terms of musical experience (Watanabe et al., 2007; Bailey and Penhune, 2010, 2012). Using this matching paradigm, the early-trained groups have demonstrated enhanced sensorimotor synchronization skills and associated differences in brain structure (Bailey et al., 2013; Steele et al., 2013). The current study takes a different approach to investigating the sensitive period hypothesis for musical training by examining a single large group of unmatched musicians (N = 77) and exploring the relationship between age of onset of musical training as a continuous variable and performance on the Rhythm Synchronization Task (RST), a previously used auditory-motor RST. Interestingly, age of onset was correlated with task performance for those who began training earlier, however, no such relationship was observed among those who began training in their later childhood years. In addition, years of formal training showed a similar pattern. However, individual working memory scores were predictive of task performance, regardless of age of onset of musical training. Overall, these results support the sensitive period hypothesis for musical training and suggest a non-linear relationship between age of onset of musical training and auditory-motor rhythm synchronization abilities, such that a relationship exists early in childhood but then plateaus later on in development, similar to maturational growth trajectories of brain regions implicated in playing music.
Peruvian Maca (Lepidium peruvianum) – III: The Effects of Cultivation Altitude on Phytochemical and Genetic Differences in the Four Prime Maca Phenotypes

In two trials, dietary and Glucosinolates’ characteristics in four Maca phenotypes have been examined with an extension into the determination of DNA sequences. Hypocotyls of the four prime phenotypes of Peruvian Maca - Lepidium peruvianum Chacon, labelled as “Yellow”, “Black”, “Red” and “Purple” were separated from mixed Maca crops cultivated in four geographically-distant locations in the Peruvian Andes at altitudes between 2,800m and 4,300 m a.s. l. It was found that at higher altitudes where Red and Purple Maca phenotypes were grown, the significantly higher (P<0.05) Glucosinolates’ concentrations, adopted as the marker of Maca physiological activity, were observed with the Purple phenotype showing the highest Glucosinolates’ content at 4,300m a.s. l. , followed by the Red-coloured hypocotyls. Black Maca showed a reversal, but also a significant (P<0.05) trend, while the Yellow phenotype showed no visible altitude-inflicted response (P>0.05) and has consistently the lowest Glucosinolates content. Thus, it is reasonable to assume that the altitude at which Red, Purple and Black phenotypes of L. peruvianum are grown, may be responsible for the variation in physiologic functionalities, leading to different than expected specific therapeutic and health benefits induced by Maca phenotypes grown at diverse altitudes. Although promising, insufficiently precise differences in DNA sequences failed to distinguish, without any reasonable doubt, four Maca phenotypes cultivated either in the same or geographically-distant locations, and harvested at different altitudes a.s. l. Further research on DNA sequences is needed, with more primers and larger number of Maca phenotypes, considering biosynthesis of secondary metabolites and adaptation pathways induced by harsh environment at altitudes where Maca is cultivated.
PADI4 polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis

The objective of the study was to investigate the association between peptidylarginine deiminase 4 (PADI4) polymorphism and susceptibility to rheumatoid arthritis (RA). An electronic searching strategy was employed to collect relevant studies on the association between PADI4 polymorphism and susceptibility to RA. The odds ratio (OR) with the 95 % confidence interval (95 % CI) was used to evaluate the RA risk presented by PADI4 polymorphism. Fixed or random effects models were selected based on heterogeneity. Publication bias was assessed using funnel plots, Begg’s test, and Egger’s test. A total of 27 studies from 21 articles were included. Six gene loci (padi4_94, 104, 92, 90, 89, and 100) were chosen for the meta-analysis. The pooled ORs (95 % CI) for allele 2 versus 1 were 1.08 (1.05–1.12), 1.17 (1.12–1.23), 1.26 (1.18–1.36), 1.17 (1.10–1.24), 1.30 (1.17–1.44), and 1.25 (1.11–1.40), respectively. All six SNPs were significantly associated with RA in Asian populations. Three SNPs (PADI4_104, 90, 89) showed significant associations, while the other three SNPs (PADI4_94, 92, 100) exhibited no associations in the European population. A dose–response relationship between allele 2 of PADI4 and the risk of RA was also identified. In conclusion, this meta-analysis suggests that PADI4 polymorphisms represent a significant risk factor for RA, especially in Asians.
Genetic and Non-Genetic Factors Affecting Birth-Weight and Adult Body Mass Index

Abstract Birthweight affects neonatal mortality and morbidity and has been used as a marker of foetal undernutrition in studies of prenatal effects on adult characteristics. It is potentially influenced by genetic and environmental influences on the mother, and effects of foetal genotype, which is partially derived from the maternal genotype. Interpretations of variation in birthweight and associated characteristics as being due to prenatal environment ignore other possible modes of materno-foetal transmission. Subjects were adult twins recruited through the Australian Twin Registry, aged 17 to 87 years, and the sample comprised 1820 men and 4048 women. Twins reported their own birthweight as part of a health questionnaire. Body Mass Index (BMI) was calculated from self-reports of height and weight. Correlations between co-twins' birthweights were high for both monozygotic (r = 0.77) and dizygotic (r = 0.67) pairs, leading to substantial estimates of shared environmental effects (56% of variance) with significant additive genetic (23%) and non-shared environmental (21%) components. Adult BMI was mainly influenced by genetic factors, both additive (36% of variance) and nonadditive (35%). The correlation between birthweight and BMI was positive, in that heavier babies became on average more obese adults. A bivariate model of birthweight and adult BMI showed significant positive genetic (rg = 0.16, p = 0.005) and environmental (re = 0.08, p = 0.000011) correlations. Intra-uterine environmental or perinatal influences shared by cotwins exercise a strong influence on birthweight, but the factors which affect both birthweight and adult BMI are partly genetic and partly non-shared environmental.
Formula for a New Foam

As the 2010 phaseout date for chlorofluorocarbons draws nearer, materials engineers are working to find replacements for these ozone-depleting chemicals in the production of plastics and other products. One team of engineers is focusing on a combination of two low-cost and environmentally benign substances--supercritical carbon dioxide and clay nanoparticles--to meet these needs. The result is a strong yet lightweight alternative that retains all the beneficial qualities of solid plastic.
Left Ventricular Oxygen Utilization in Intact Dogs: Effect of Systemic Hemodynamic Factors

The influence of acute changes in systemic hemodynamics on the rate of oxygen utilization by the left ventricle has been studied in intact anesthetized dogs. Certain types of hemodynamic changes caused reproducible alterations in the relationship between oxygen consumption of the left ventricle and its external mechanical work. The relationship of left ventricular minute oxygen consumption to the product of mean systolic aortic pressure and systolic ejection period per minute was constant over an extreme range of varied types of hemodynamic alterations. Changes in oxygen consumption were proportionately less than concomitant changes in heart rate. These findings are in accord with previous studies of isolated heart preparations.
Birth and Rapid Subcellular Adaptation of a Hominoid-Specific CDC14 Protein

Gene duplication was prevalent during hominoid evolution, yet little is known about the functional fate of new ape gene copies. We characterized the CDC14B cell cycle gene and the functional evolution of its hominoid-specific daughter gene, CDC14Bretro. We found that CDC14B encodes four different splice isoforms that show different subcellular localizations (nucleus or microtubule-associated) and functional properties. A microtubular CDC14B variant spawned CDC14Bretro through retroposition in the hominoid ancestor 18–25 million years ago (Mya). CDC14Bretro evolved brain-/testis-specific expression after the duplication event and experienced a short period of intense positive selection in the African ape ancestor 7–12 Mya. Using resurrected ancestral protein variants, we demonstrate that by virtue of amino acid substitutions in distinct protein regions during this time, the subcellular localization of CDC14Bretro progressively shifted from the association with microtubules (stabilizing them) to an association with the endoplasmic reticulum. CDC14Bretro evolution represents a paradigm example of rapid, selectively driven subcellular relocalization, thus revealing a novel mode for the emergence of new gene function.
A heating stage up to 1173 K for X-ray diffraction studies in the whole orientation space

A multi-purpose heating attachment designed primarily for X-ray four-circle diffractometers but applicable also for classical powder diffraction is presented. When working in reflection geometry, the air-cooled heating stage allows diffraction studies to be performed on plate-like samples up to 1173 K in the whole orientation space. This paper gives a detailed description of the assembly and important technical specifications for the performance of experiments. The heating characteristics of the heating stage, the displacement of the sample from the goniometer centre as a result of thermal expansion and the influence of the protecting dome on the diffraction experiment are presented. The simple technical construction, the low weight, the small size and good heating performance make this equipment a general purpose heating attachment for X-ray diffraction experiments in reflection geometry.
Oncostatin M receptor is a novel therapeutic target in cervical squamous cell carcinoma

Cervical carcinoma is the second most common cause of cancer deaths in women worldwide. Treatments have not changed for decades and survival rates for advanced disease remain low. An exciting new molecular target for the treatment of cervical squamous cell carcinoma (SCC), and possibly for SCCs at other anatomical sites, is the oncostatin M receptor (OSMR). This cell surface cytokine receptor is commonly copy number gained and overexpressed in advanced cervical SCC, changes that are associated with significantly worse clinical outcomes. OSMR overexpression in cervical SCC cells results in enhanced responsiveness to the major ligand oncostatin M (OSM), which induces several pro‐malignant effects, including a pro‐angiogenic phenotype and increased cell migration and invasiveness. OSMR is a strong candidate for antibody‐mediated inhibition, a strategy that has had a major impact on haematological malignancies and various solid tumours such as HER2‐positive breast cancers. © 2013 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Helical piles: an innovative foundation design option for offshore wind turbines

Offshore wind turbines play a key part in the renewable energy strategy in the UK and Europe as well as in other parts of the world (for example, China). The majority of current developments, certainly in UK waters, have taken place in relatively shallow water and close to shore. This limits the scale of the engineering to relatively simple structures, such as those using monopile foundations, and these have been the most common design to date, in UK waters. However, as larger turbines are designed, or they are placed in deeper water, it will be necessary to use multi-footing structures such as tripods or jackets. For these designs, the tension on the upwind footing becomes the critical design condition. Driven pile foundations could be used, as could suction-installed foundations. However, in this paper, we present another concept—the use of helical pile foundations. These foundations are routinely applied onshore where large tension capacities are required. However, for use offshore, a significant upscaling of the technology will be needed, particularly of the equipment required for installation of the piles. A clear understanding of the relevant geotechnical engineering will be needed if this upscaling is to be successful.
Biosynthesis of Cryptic Lipopolysaccharide Glycoforms in Haemophilus influenzae Involves a Mechanism Similar to That Required for O-Antigen Synthesis

ABSTRACT It is generally thought that mucosal bacterial pathogens of the genera Haemophilus, Neisseria, and Moraxella elaborate lipopolysaccharide (LPS) that is fundamentally different from that of enteric organisms that express O-specific polysaccharide side chains. Haemophilus influenzae elaborates short-chain LPS that has a role in the pathogenesis of H. influenzae infections. We show that the synthesis of LPS in this organism can no longer be as clearly distinguished from that in other gram-negative bacteria that express an O antigen. We provide evidence that a region of the H. influenzae genome, the hmg locus, is involved in the synthesis of glycoforms in which tetrasaccharide units are added en bloc, not stepwise, to the normal core glycoforms, similar to the biosynthesis of an O-antigen.