Miracle-dz/UniFAR-FTUs huggingface dataset:
Parental Serotonin Transporter Polymorphism (5-HTTLPR) Moderates Associations of Stress and Child Behavior With Parenting Behavior

The serotonin transporter-linked polymorphic region (5-HTTLPR) is associated with caregiving in nonhuman animals and with affective and cognitive correlates of human parenting, yet its association with human parenting is largely unknown. Using a well-characterized sample of parents and offspring, we evaluated the association of parental 5-HTTLPR with observed positive and negative parenting behavior, as well as its biologically plausible moderation of child-related stress and disruptive child behavior as predictors of parenting. One hundred and sixty-two parents (86% mothers) and their 6- to 9-year-old children with and without attention-deficit/hyperactivity disorder were ascertained using multiple methods including structured interviews, rating scales, and observed parent-child interaction, yielding strong measures of key constructs. Controlling for multiple youth-level (e.g., sex, 5-HTTLPR genotype, disruptive behavior) and parent-level (e.g., demographics, depression, attention-deficit/hyperactivity disorder) factors, parents with an S allele exhibited significantly less observed positive parenting than those with the LL genotype. Significant Gene × Environment interactions were also observed: Child-related stress was negatively associated with observed parental negativity among SS/SL genotype parents but not LL genotype parents; next, observed disruptive child behavior was positively associated with parental negativity for both genotypes, but the effect was strongest in SS/SL parents. These preliminary findings suggest that parental 5-HTTLPR is uniquely associated with positive and negative parenting behavior, with more specific patterns according to child-related stress and disruptive child behavior. We consider implications for future research evaluating genetic influences on parenting as well as considerations for designing and delivering parenting-based interventions.
The Gene or Not the Gene—That Is the Question

Embryonic stem cells have had a significant impact on understanding gene function and gene interactions through the use of genetically engineered mice. However, the genetic context (ie, mouse strain) in which these modifications in alleles are made may have a considerable effect on the phenotypic changes identified in these mice. In addition, tissue- and time-specific gene expression systems may generate unanticipated outcomes. This article discusses the history of embryonic stem cells, reviews how mouse strain can affect phenotype (using specific examples), and examines some of the caveats of conditional gene expression systems.
First Trimester Screening of Circulating C19MC microRNAs Can Predict Subsequent Onset of Gestational Hypertension

Objective The objective of the study was to evaluate risk assessment for gestational hypertension based on the profile of circulating placental specific C19MC microRNAs in early pregnancy. Study design The prospective longitudinal cohort study of women enrolled at first trimester screening at 10 to 13 weeks was carried out (n = 267). Relative quantification of placental specific C19MC microRNAs (miR-516-5p, miR-517*, miR-518b, miR-520a*, miR-520h, miR-525 and miR-526a) was determined in 28 normal pregnancies and 18 pregnancies which developed gestational hypertension using real-time PCR and a comparative Ct method relative to synthetic C. elegans microRNA (cel-miR-39). Results Increased extracellular C19MC microRNA plasmatic levels (miR-516-5p, p<0.001; miR-517*, p = 0.007; miR-520h, p<0.001; miR-518b, p = 0.002) were detected in patients destined to develop gestational hypertension. MiR-520h had the best predictive performance with a PPV of 84.6% at a 7.1% false positive rate. The combination of miR-520h and miR-518b was able to predict 82.6% of women at the same false positive rate. The overall predictive capacity of single miR-518b (73.3% at 14.3% FPR), miR-516-5p (70.6% at 17.9% FPR) and miR-517* (57.9% at 28.6% FPR) biomarkers was lower. Conclusion The study brought interesting finding that the up-regulation of miR-516-5p, miR-517*, miR-520h and miR-518b is associated with a risk of later development of gestational hypertension. First trimester screening of extracellular miR-520h alone or in combination with miR-518b identified a significant proportion of women with subsequent gestational hypertension.
Lichen planopilaris is characterized by immune privilege collapse of the hair follicle's epithelial stem cell niche

Lichen planopilaris (LPP) is a chronic inflammatory disease of unknown pathogenesis that leads to permanent hair loss. Whilst destruction of epithelial hair follicle stem cells (eHFSCs) that reside in an immunologically protected niche of the HF epithelium, the bulge, is a likely key event in LPP pathogenesis, this remains to be demonstrated. We have tested the hypotheses that bulge immune privilege (IP) collapse and inflammation‐induced eHFSC death are key components in the pathogenesis of LPP. Biopsies of lesional and non‐lesional scalp skin from adult LPP patients (n = 42) were analysed by quantitative (immuno)histomorphometry, real‐time quantitative polymerase chain reaction (qRT–PCR), laser capture microdissection and microarray analysis, or skin organ culture. At both the protein and transcriptional level, lesional LPP HFs showed evidence for bulge IP collapse (ie increased expression of MHC class I and II, β2microglobulin; reduced TGFβ2 and CD200 expression). This was accompanied by a Th1‐biased cytotoxic T cell response (ie increased CD8+ GranzymeB+ T cells and CD123+ plasmacytoid dendritic cells, with increased CXCR3 expression) and increased expression of interferon‐inducible chemokines (CXCL9/10/11). Interestingly, lesional LPP eHFSCs showed both increased proliferation and apoptosis in situ. Microarray analysis revealed a loss of eHFSC signatures and increased expression of T cell activation/binding markers in active LPP, while bulge PPARγ transcription was unaltered compared to non‐lesional LPP HFs. In organ culture of non‐lesional LPP skin, interferon‐γ (IFNγ) induced bulge IP collapse. LPP is an excellent model disease for studying and preventing immune destruction of human epithelial stem cells in situ. These novel findings raise the possibility that LPP represents an autoimmune disease in whose pathogenesis IFNγ‐induced bulge IP collapse plays an important role. Therapeutically, bulge IP protection/restoration may help to better manage this highly treatment‐resistant cicatricial alopecia. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
High‐throughput screening of soluble recombinant proteins

The aims of high‐throughput (HTP) protein production systems are to obtain well‐expressed and highly soluble proteins, which are preferred candidates for use in structure–function studies. Here, we describe the development of an efficient and inexpensive method for parallel cloning, induction, and cell lysis to produce multiple fusion proteins in Escherichia coli using a 96‐well format. Molecular cloning procedures, used in this HTP system, require no restriction digestion of the PCR products. All target genes can be directionally cloned into eight different fusion protein expression vectors using two universal restriction sites and with high efficiency (>95%). To screen for well‐expressed soluble fusion protein, total cell lysates of bacteria culture (∼1.5 mL) were subjected to high‐speed centrifugation in a 96‐tube format and analyzed by multiwell denaturing SDS‐PAGE. Our results thus far show that 80% of the genes screened show high levels of expression of soluble products in at least one of the eight fusion protein constructs. The method is well suited for automation and is applicable for the production of large numbers of proteins for genome‐wide analysis.
Body composition, atherogenic risk factors and apolipoproteins following growth hormone treatment

We studied the change in atherogenic risk factors in 27 children, 21 boys and 6 girls, 6 to 14 years of age. with growth hormone deficiency during 12 months of growth hormone replacement therapy. Changes in body composition and lipid profile during growth hormone treatment were evaluated. The atherogenic index was calculated using the equation [(total cholesterol ‐ high‐density lipoprotein cholesterol)(apolipoprotein B)] / [(apolipoprotein A1)(high‐density lipoprotein cholesterol)]. Body fat decreased (p < 0.01), associated with an increase in lean body mass (p < 0.01). Total cholesterol and high‐density lipoprotein cholesterol showed no significant changes. The atherogenic index significantly decreased from 1.44 ± 0.60 to 1.09 ± 0.52 (p < 0.01) after 12 months. Apolipoproteins Cu and Cm increased throughout the study period (p < 0.01). Lipoprotein(a) and apolipoproteins A1, B and B/A1 ratio did not change significantly. In conclusion, growth hormone treatment improved body composition and reduced atherogenic risk factors in children with growth hormone deficiency.
A relocatable EnKF ocean data assimilation tool for heterogeneous observational networks

This study investigates the performance of a multivariate Ensemble Kalman Filter coupled with a relocatable limited-area configuration of the Regional Ocean Modeling System to predict ocean states by assimilating a heterogeneous data set involving underwater gliders and ship observations. In particular, two different ensemble initialization techniques are exploited and evaluated with the dataset collected during the REP13-MED experiment conducted by CMRE on 5-20 August 2013 in the Ligurian Sea. Results show that the forecast skill is significantly improved when the free ensemble is initialized from a long term climatology of the Mediterranean Forecast System. In particular the results obtained reveal significant increased skills in salinity forecasting in comparison with the previous ensemble initialization technique [6].
Aerobic and anaerobic determinants of repeated sprint ability in team sports athletes

The aim of this study was to examine in team sports athletes the relationship between repeated sprint ability (RSA) indices and both aerobic and anaerobic fitness components. Sixteen team-sport players were included (age, 23.4 ± 2.3 years; weight, 71.2 ± 8.3 kg; height, 178 ± 7 cm; body mass index, 22.4 ± 2 kg · m−2; estimated VO2max, 54.16 ± 3.5 mL · kg−1 · min−1). Subjects were licensed in various team sports: soccer (n = 8), basketball (n = 5), and handball (n = 3). They performed 4 tests: the 20 m multi-stage shuttle run test (MSRT), the 30-s Wingate test (WingT), the Maximal Anaerobic Shuttle Running Test (MASRT), and the RSA test (10 repetitions of 30 m shuttle sprints (15 + 15 m with 180° change of direction) with 30 s passive recovery in between). Pearson's product moment of correlation among the different physical tests was performed. No significant correlations were found between any RSA test indices and WingT. However, negative correlations were found between MASRT and RSA total sprint time (TT) and fatigue index (FI) (r = -0.53, p < 0.05 and r = -0.65, p < 0.01, respectively). No significant relationship between VO2max and RSA peak sprint time (PT) and total sprint time (TT) was found. Nevertheless, VO2max was significantly correlated with the RSA FI (r = -0.57, p < 0.05). In conclusion, aerobic fitness is an important factor influencing the ability to resist fatigue during RSA exercise. Our results highlighted the usefulness of MASRT, in contrast to WingT, as a specific anaerobic testing procedure to identify the anaerobic energy system contribution during RSA.
Indocyanine green angiography in a case of punctate inner choroidopathy.

EDITOR,-The term punctate inner choroidopathy (PIC) was first applied by Watzke et al I in 1984, although similar lesions had previously been described by Doran and Hamilton.2 Classically, PIC occurs in moderately myopic young women, and is characterised by the development of unilateral blurred vision, often associated with photopsia. On examination multiple, white-yellow, subretinal lesions are observed concentrated at the posterior pole. Fewer similar lesions are also often seen in the asymptomatic eye. Signs of intraocular inflammation are absent. Visual acuity is only slightly affected unless the lesions are subfoveal or (as in about 30% of cases) subsequent choroidal neovascularisation develops. The aetiology of this condition is as yet unclear. We report here a patient who appeared to present with features typical of PIC, and who showed unusual, and in our experience unique, abnormalities of the choroidal vasculature as demonstrated by indocyanine green angiography (ICG). To our knowledge this is the first report of ICG findings in this condition.
Effects of exercise training on oxygen uptake in coronary heart disease: a systematic review and meta‐analysis

It is not known to what extent exercise programs increase maximal oxygen uptake (VO2max) in patients with coronary heart diseases (CHD). The purpose of this study is to determine the effect of exercise interventions on VO2max in subjects with CHD. Database search of randomized controlled trials was conducted from PubMed. Studies were included that reported the characteristics and effects of exercise interventions in subjects with CHD, included a non‐exercise control group and measured VO2max using direct measurement method. Eighteen studies were eligible. Exercise interventions increased VO2max by 2.6 ± 1.6 and 0.3 ± 1.4 mL/kg/min in the training and control groups, respectively. The net difference in the change of VO2max between the groups was 2.3 mL/kg/min with a standardized mean difference of 0.60 [95% CI 0.47, 0.74] (P<0.001). Aerobic training led to a larger difference in VO2max between the groups than other training modes. Over 6 months of training period and training started within 3 months after a cardiac event also had a significant effect on VO2max. This analysis showed that a long exercise training period starting soon after a cardiac event improved VO2max in patients with CHD most effectively. In future studies, the training programs should be designed carefully as even larger improvements in VO2max may be possible.
Compressive Sensing Based Design of Sparse Tripole Arrays

This paper considers the problem of designing sparse linear tripole arrays. In such arrays at each antenna location there are three orthogonal dipoles, allowing full measurement of both the horizontal and vertical components of the received waveform. We formulate this problem from the viewpoint of Compressive Sensing (CS). However, unlike for isotropic array elements (single antenna), we now have three complex valued weight coefficients associated with each potential location (due to the three dipoles), which have to be simultaneously minimised. If this is not done, we may only set the weight coefficients of individual dipoles to be zero valued, rather than complete tripoles, meaning some dipoles may remain at each location. Therefore, the contributions of this paper are to formulate the design of sparse tripole arrays as an optimisation problem, and then we obtain a solution based on the minimisation of a modified l1 norm or a series of iteratively solved reweighted minimisations, which ensure a truly sparse solution. Design examples are provided to verify the effectiveness of the proposed methods and show that a good approximation of a reference pattern can be achieved using fewer tripoles than a Uniform Linear Array (ULA) of equivalent length.
A single institution experience using the LigaSure vessel sealing system in video-assisted thoracoscopic surgery for primary spontaneous pneumothorax

Abstract This study sought to report our 6-year experience with the LigaSure vessel sealing system (LVSS) in video-assisted thoracoscopic surgery (VATS) for primary spontaneous pneumothorax. A series of 180 consecutive patients with primary spontaneous pneumothorax were operated on in our institution from May 2005 to December 2010. Intraoperatively, large lesions (bullae or blebs) with a diameter more than 2 cm were resected by staplers, and the residual lesions were treated by LVSS. LVSS was also used to ablate the apical area when no lesions were found. Conventional apical pleural abrasion was done in all cases. All patients were successfully treated using VATS with minimal perioperative bleeding. The mean operating time was 76 minutes (range, 43–160 minutes) for single-side procedures and 169 minutes (range, 135–195 minutes) for bilateral procedures, the mean number of applied staples was 1.93 per patient (range, 0–8 days), the duration of drainage was 3.8 days (range, 2–15 days), and the duration of hospital stay was 5.8 days (range, 3–16 days). Postoperative complications included persistent air leak (> 5 days) in 11 cases (6.1%) and residual pneumothorax in 6 (3.3%). None required reoperation. The mean duration of follow-up was 57 months (range, 24–105 months). Recurrence was seen in three cases (1.7%), and all underwent another operation thereafter. None of the lesions in the relapse cases received ablation with LVSS in the first operation. LVSS can optimize VATS for primary spontaneous pneumothorax and reduces the use of single-use staples. The method is safe, easy to use, and cost-effective and produces satisfactory results.
Maintenance of DNA Methylation during the Arabidopsis Life Cycle Is Essential for Parental Imprinting[W]

Imprinted genes are expressed predominantly from either their paternal or their maternal allele. To date, all imprinted genes identified in plants are expressed in the endosperm. In Arabidopsis thaliana, maternal imprinting has been clearly demonstrated for the Polycomb group gene MEDEA (MEA) and for FWA. Direct repeats upstream of FWA are subject to DNA methylation. However, it is still not clear to what extent similar cis-acting elements may be part of a conserved molecular mechanism controlling maternally imprinted genes. In this work, we show that the Polycomb group gene FERTILIZATION-INDEPENDENT SEED2 (FIS2) is imprinted. Maintenance of FIS2 imprinting depends on DNA methylation, whereas loss of DNA methylation does not affect MEA imprinting. DNA methylation targets a small region upstream of FIS2 distinct from the target of DNA methylation associated with FWA. We show that FWA and FIS2 imprinting requires the maintenance of DNA methylation throughout the plant life cycle, including male gametogenesis and endosperm development. Our data thus demonstrate that parental genomic imprinting in plants depends on diverse cis-elements and mechanisms dependent or independent of DNA methylation. We propose that imprinting has evolved under constraints linked to the evolution of plant reproduction and not by the selection of a specific molecular mechanism.
How does CT image noise affect 3D deformable image registration for image-guided radiotherapy planning?

PURPOSE To measure the sensitivity of deformable image registration to image noise. Deformable image registration can be used to map organ contours and other treatment planning data from one CT to another. These CT studies can be acquired with either conventional fan-beam CT systems or more novel cone-beam CT techniques. However, cone-beam CT images can have higher noise levels than fan-beam CT, which might reduce registration accuracy. We have investigated the effect of image quality differences on the deformable registration of fan-beam CTs and CTs with simulated cone-beam noise. METHOD Our study used three CT studies for each of five prostate patients. Each CT was contoured by three experienced radiation oncologists. For each patient, one CT was designated the source image and the other two were target images. A deformable image registration process was used to register each source CT to each target CT and then transfer the manually drawn treatment planning contours from the source CT to the target CTs. The accuracy of the automatically transferred contours (and thus of the deformable registration process) was assessed by comparing them to the manual contours on the target CTs, with the differences evaluated with respect to interobserver variability in the manual contours. Then each of the target CTs was modified to include increased noise characteristic of cone-beam CT and the tests were repeated. Changes in registration accuracy due to increased noise were detected by monitoring changes in the automatically transferred contours. RESULTS We found that the additional noise caused no significant loss of registration accuracy at magnitudes that exceeded what would normally be found in an actual cone-beam CT. SUMMARY We conclude that noise levels in cone-beam CTs that might reduce manual contouring accuracy do not reduce image registration and automatic contouring accuracy.
CD133 is a modifier of hematopoietic progenitor frequencies but is dispensable for the maintenance of mouse hematopoietic stem cells

Pentatransmembrane glycoprotein prominin-1 (CD133) is expressed at the cell surface of multiple somatic stem cells, and it is widely used as a cell surface marker for the isolation and characterization of human hematopoietic stem cells (HSCs) and cancer stem cells. CD133 has been linked on a cell biological basis to stem cell-fate decisions in human HSCs and emerges as an important physiological regulator of stem cell maintenance and expansion. Its expression and physiological relevance in the murine hematopoietic system is nevertheless elusive. We show here that CD133 is expressed by bone marrow-resident murine HSCs and myeloid precursor cells with the developmental propensity to give rise to granulocytes and monocytes. However, CD133 is dispensable for the pool size and function of HSCs during steady-state hematopoiesis and after transplantation, demonstrating a substantial species difference between mouse and man. Blood cell numbers in the periphery are normal; however, CD133 appears to be a modifier for the development of growth-factor responsive myeloerythroid precursor cells in the bone marrow under steady state and mature red blood cells after hematopoietic stress. Taken together, these studies show that CD133 is not a critical regulator of hematopoietic stem cell function in mouse but that it modifies frequencies of growth-factor responsive hematopoietic progenitor cells during steady state and after myelotoxic stress in vivo.
Live imaging of X chromosome reactivation dynamics in early mouse development can discriminate naïve from primed pluripotent stem cells

Pluripotent stem cells can be classified into two distinct states, naïve and primed, which show different degrees of potency. One difficulty in stem cell research is the inability to distinguish these states in live cells. Studies on female mice have shown that reactivation of inactive X chromosomes occurs in the naïve state, while one of the X chromosomes is inactivated in the primed state. Therefore, we aimed to distinguish the two states by monitoring X chromosome reactivation. Thus far, X chromosome reactivation has been analysed using fixed cells; here, we inserted different fluorescent reporter gene cassettes (mCherry and eGFP) into each X chromosome. Using these knock-in ‘Momiji’ mice, we detected X chromosome reactivation accurately in live embryos, and confirmed that the pluripotent states of embryos were stable ex vivo, as represented by embryonic and epiblast stem cells in terms of X chromosome reactivation. Thus, Momiji mice provide a simple and accurate method for identifying stem cell status based on X chromosome reactivation. Highlighted Article: Reporter mice harbouring gene cassettes encoding two different fluorescent proteins inserted into specific loci in the X chromosomes are used to study X chromosome status in vivo.