Miracle-dz/UniFAR-FTUs huggingface dataset:
Whole Genome Sequencing and a New Bioinformatics Platform Allow for Rapid Gene Identification in D. melanogaster EMS Screens

Forward genetic screens in Drosophila melanogaster using ethyl methanesulfonate (EMS) mutagenesis are a powerful approach for identifying genes that modulate specific biological processes in an in vivo setting. The mapping of genes that contain randomly-induced point mutations has become more efficient in Drosophila thanks to the maturation and availability of many types of genetic tools. However, classic approaches to gene mapping are relatively slow and ultimately require extensive Sanger sequencing of candidate chromosomal loci. With the advent of new high-throughput sequencing techniques, it is increasingly efficient to directly re-sequence the whole genome of model organisms. This approach, in combination with traditional chromosomal mapping, has the potential to greatly simplify and accelerate mutation identification in mutants generated in EMS screens. Here we show that next-generation sequencing (NGS) is an accurate and efficient tool for high-throughput sequencing and mutation discovery in Drosophila melanogaster. As a test case, mutant strains of Drosophila that exhibited long-term survival of severed peripheral axons were identified in a forward EMS mutagenesis. All mutants were recessive and fell into a single lethal complementation group, which suggested that a single gene was responsible for the protective axon degenerative phenotype. Whole genome sequencing of these genomes identified the underlying gene ect4. To improve the process of genome wide mutation identification, we developed Genomes Management Application (GEM.app, https://genomics.med.miami.edu), a graphical online user interface to a custom query framework. Using a custom GEM.app query, we were able to identify that each mutant carried a unique non-sense mutation in the gene ect4 (dSarm), which was recently shown by Osterloh et al. to be essential for the activation of axonal degeneration. Our results demonstrate the current advantages and limitations of NGS in Drosophila and we introduce GEM.app as a simple yet powerful genomics analysis tool for the Drosophila community. At a current cost of <$1,000 per genome, NGS should thus become a standard gene discovery tool in EMS induced genetic forward screens.
Single-cell gene profiling defines differential progenitor subclasses in mammalian neurogenesis

Cellular diversity of the brain is largely attributed to the spatial and temporal heterogeneity of progenitor cells. In mammalian cerebral development, it has been difficult to determine how heterogeneous the neural progenitor cells are, owing to dynamic changes in their nuclear position and gene expression. To address this issue, we systematically analyzed the cDNA profiles of a large number of single progenitor cells at the mid-embryonic stage in mouse. By cluster analysis and in situ hybridization, we have identified a set of genes that distinguishes between the apical and basal progenitors. Despite their relatively homogeneous global gene expression profiles, the apical progenitors exhibit highly variable expression patterns of Notch signaling components, raising the possibility that this causes the heterogeneous division patterns of these cells. Furthermore, we successfully captured the nascent state of basal progenitor cells. These cells are generated shortly after birth from the division of the apical progenitors, and show strong expression of the major Notch ligand delta-like 1, which soon fades away as the cells migrate in the ventricular zone. We also demonstrated that attenuation of Notch signals immediately induces differentiation of apical progenitors into nascent basal progenitors. Thus, a Notch-dependent feedback loop is likely to be in operation to maintain both progenitor populations.
Tissue Doppler Imaging Differentiates Physiological From Pathological Pressure-Overload Left Ventricular Hypertrophy in Rats

Background—The myocardial velocity gradient (MVG) is a recent index of regional myocardial function derived from endocardial and epicardial velocities obtained by tissue Doppler imaging (TDI). This index might be useful for discriminating between physiological and pathological left ventricular hypertrophy (LVH) and for documenting the early transition from compensated LVH to heart failure. We sought to compare MVG measured across the left ventricular posterior wall between normal rats and rats with physiological (exercise) and pathological (pressure-overload) LVH. Methods and Results—Wistar rats were assigned to one of the following groups: sedentary, exercise (swimming), and 2-month or 9-month abdominal aortic banding. Compared with sedentary rats, exercise and 2-month banding led to similar and significant LVH. After 2-month banding, conventional parameters of systolic function (left ventricular fractional shortening and dP/dtmax) were not affected. However, systolic and diastolic MVG were similar in exercise and sedentary rats but were significantly lower in rats with aortic banding. Aortic debanding after 2 months led to a full recovery of MVG, whereas MVG remained decreased when debanding was performed after 9 months. Conclusions—Myocardial contraction and relaxation assessed by TDI were impaired in pressure-overload LVH but not in exercise LVH. Therefore, TDI is more sensitive than conventional echocardiography for assessing myocardial dysfunction in pressure-overload LVH and for predicting early recovery in myocardial function after loading conditions normalization.
Air Pollutants, Climate, and the Prevalence of Pediatric Asthma in Urban Areas of China

Background. Prevalence of childhood asthma varies significantly among regions, while its reasons are not clear yet with only a few studies reporting relevant causes for this variation. Objective. To investigate the potential role of city-average levels of air pollutants and climatic factors in order to distinguish differences in asthma prevalence in China and explain their reasons. Methods. Data pertaining to 10,777 asthmatic patients were obtained from the third nationwide survey of childhood asthma in China's urban areas. Annual mean concentrations of air pollutants and other climatic factors were obtained for the same period from several government departments. Data analysis was implemented with descriptive statistics, Pearson correlation coefficient, and multiple regression analysis. Results. Pearson correlation analysis showed that the situation of childhood asthma was strongly linked with SO2, relative humidity, and hours of sunshine (p < 0.05). Multiple regression analysis indicated that, among the predictor variables in the final step, SO2 was found to be the most powerful predictor variable amongst all (β = −19.572, p < 0.05). Furthermore, results had shown that hours of sunshine (β = −0.014, p < 0.05) was a significant component summary predictor variable. Conclusion. The findings of this study do not suggest that air pollutants or climate, at least in terms of children, plays a major role in explaining regional differences in asthma prevalence in China.
Somatic Cell Exchange Occurs between Mouse Fetal Gonads and Mesonephroi during in vitro Culture

Mesonephric cell contribution to the developing mouse gonad has previously been shown to be male-specific in in vitro culture models. This study shows that somatic cell exchange occurs between fetal mouse mesonephroi and gonads during in vitro culture of assembled tissues. Assembling gonads with cell marker-carrying mesonephroi and vice versa identified cell exchange. Two different cell markers were used. One of the markers was the thymidine analogue bromodeoxyuridine (BrdU), which was added to the culture medium during an initial culture period before in vitro culture of assembled tissues in medium without BrdU. The other was bacterial β-galactosidase, which is expressed ubiquitously in tissues from the transgenic mouse strain ROSA26. The tissues were taken from either 10.5- or 11.5-day-old mouse fetuses, and the assembled tissues were cultured for 36–60 h. Both cell markers demonstrated the occurrence of a cell exchange in both directions between the mesonephros and the gonad. The cell contribution was found to be minor and independent of the initial age of the tissue and hours in culture. Further, mesonephric cell contribution was not male-specific. Cell exchange between the two tissues may be due to growth between the assembled tissues rather than active signal-regulated migration. It is suggested that in vitro culture models may not be applicable for investigating mesonephric cell contribution to the developing mouse gonad.
Mannose-Binding Lectin Is a Regulator of Inflammation That Accompanies Myocardial Ischemia and Reperfusion Injury1

The mannose-binding lectin (MBL), a circulating pattern recognition molecule, recognizes a wide range of infectious agents with resultant initiation of the complement cascade in an Ab-independent manner. MBL recognizes infectious non-self and altered self in the guise of apoptotic and necrotic cells. In this study, we demonstrate that mice lacking MBL, and hence are devoid of MBL-dependent lectin pathway activation but have fully active alternative and classical complement pathways, are protected from cardiac reperfusion injury with resultant preservation of cardiac function. Significantly, mice that lack a major component of the classical complement pathway initiation complex (C1q) but have an intact MBL complement pathway, are not protected from injury. These results suggest that the MBL-dependent pathway of complement activation is a key regulator of myocardial reperfusion ischemic injury. MBL is an example of a pattern recognition molecule that plays a dual role in modifying inflammatory responses to sterile and infectious injury.
Ground reaction forces and knee kinetics during single and repeated badminton lunges

ABSTRACT Repeated movement (RM) lunge that frequently executed in badminton might be used for footwear evaluation. This study examined the influence of single movement (SM) and RM lunges on the ground reaction forces (GRFs) and knee kinetics during the braking phase of a badminton lunge step. Thirteen male university badminton players performed left-forward lunges in both SM and RM sessions. Force platform and motion capturing system were used to measure GRFs and knee kinetics variables. Paired t-test was performed to determine any significant differences between SM and RM lunges regarding mean and coefficient of variation (CV) in each variable. The kinetics results indicated that compared to SM lunges, the RM lunges had shorter contact time and generated smaller maximum loading rate of impact force, peak knee anterior-posterior force, and peak knee sagittal moment but generated larger peak horizontal resultant forces (Ps < 0.05). Additionally, the RM lunges had lower CV for peak knee medial-lateral and vertical forces (Ps < 0.05). These results suggested that the RM testing protocols had a distinct loading response and adaptation pattern during lunge and that the RM protocol showed higher within-trial reliability, which may be beneficial for the knee joint loading evaluation under different interventions.
Refining the Binding of the Escherichia coli Flagellar Master Regulator, FlhD4C2, on a Base-Specific Level

ABSTRACT The Escherichia coli flagellar master regulator, FlhD4C2, binds to the promoter regions of flagellar class II genes, yet, despite extensive analysis of the FlhD4C2-regulated promoter region, a detailed consensus sequence has not emerged. We used in vitro and in vivo experimental approaches to determine the nucleotides in the class II promoter, fliAp, required for the binding and function of FlhD4C2. FlhD4C2 protects 48 bp (positions −76 to −29 relative to the σ70-dependent transcriptional start site) in the fliA promoter. We divided the 48-bp footprint region into 5 sections to determine the requirement of each DNA segment for the binding and function of FlhD4C2. Results from an in vitro binding competition assay between the wild-type FlhD4C2-protected fragment and DNA fragments possessing mutations in one section of the 48-bp protected region showed that only one-third of the 48 bp protected by FlhD4C2 is required for FlhD4C2 binding and fliA promoter activity. This in vitro binding result was also seen in vivo with fliA promoter-lacZ fusions carrying the same mutations. Only seven bases (A12, A15, T34, A36, T37, A44, and T45) are absolutely required for the promoter activity. Moreover, A12, A15, T34, T37, and T45 within the 7 bases are highly specific to fliA promoter activity, and those bases form an asymmetric recognition site for FlhD4C2. The implications of the asymmetry of the FlhD4C2 binding site and its potential impact on FlhD4C2 are discussed.
Radio luminosities and classificatory criteria of BL Lacertae objects

Using the sample of radio-selected BL Lacertae objects (RBLs) and X-ray selected BL Lacertae objects (XBLs) presented by Sambruna et al. ([CITE]), we calculated the luminosities in radio, optical and X-ray of each source and made a statistical analysis among the luminosities at different wave-bands, broad-band spectral indices from radio to X-ray ($\alpha_{\rm rx}$) and peak frequencies ($\nu_{\rm p}$). Our results are as follows: (i) there is a positive correlation between radio luminosity L r and $\alpha_{\rm rx}$ and a negative correlation between L r and $\nu_{\rm p}$. High-energy peak BL Lacs (HBLs) and low-energy peak BL Lacs (LBLs) can be distinguished very well; the dividing lines are probably those of $\log {L_{\rm r}}=43.25$ (erg/s) and $\alpha_{\rm rx}>$(or $\leq $)0.75 for $\log L_{\rm r}$–$\alpha_{\rm rx}$ plot and those of $\log L_{\rm r}\leq 43.25$ (erg/s) and $\log {\nu_{\rm p}}>14.7$ for the ${\bf\log}\,L_{\rm r}$ – ${\bf\log}\,\nu_{\rm p}$ plot; (ii) there is a weak positive correlation between optical luminosity L o and $\alpha_{\rm rx}$ and a negative weak correlation between $L_{\rm o}$ and $\nu_{\rm p}$; (iii) there is no correlation between X-ray luminosity L x and $\alpha_{\rm rx}$ or between L x and $\nu_{\rm p}$. From our analysis, we find that synchrotron radiation is the main X-ray radiation mechanism for HBLs while inverse Compton scattering is dominant for LBLs.
Khat chewing is a risk factor for acute myocardial infarction: a case-control study.

AIM Khat chewing is a common habit in Yemen and east African countries. Millions of people chew khat leaves daily for its euphoric and energetic effects and to increase alertness. Cathinone, the main active substance in fresh khat leaves, has sympathomimetic effects which increase heart rate and blood pressure. The aim was to examine the hypothesis that khat chewing is a risk factor for acute myocardial infarction (AMI) using a hospital-based matched case-control study. METHOD Between 1997 and 1999, we selected 100 patients admitted to the Al-Thawra teaching hospital Sana'a ICU, Yemen with acute myocardial infarction. 100 control subjects, matched to cases for sex and age, were recruited from the outpatients clinics of the same hospital. A questionnaire was completed for case and control groups covering personal history of khat chewing, smoking, hypertension, diabetes and any family history of myocardial infarction. A blood sample was collected for performing lipid profiles. Cases and controls were compared by analysis conducted using conditional logistic regression which corrected for baseline imbalances leading to less biased estimations of odds ratio (OR). The risk associated with each classical factor and khat chewing habits was then investigated. OR values greater than 2.5 indicated a significant risk factor. RESULTS Khat chewing was significantly higher among the AMI case group than control group (OR = 5.0, 95% CI 1.9-13.1). A dose-response relationship was observed, the heavy khat chewers having a 39-fold increased risk of AMI. CONCLUSION This study indicates that khat chewing is associated with AMI and is an independent dose-related risk factor for the development of myocardial infarction.
Dynamic typing in a statically-typed language

Statically-typed programming languages allow earlier error checking, better enforcement of disciplined programming styles, and generation of more efficient object code than languages where all type-consistency checks are performed at runtime. However, even in statically-type languages, there is often the need to deal with data whose type cannot be known at compile time. To handle such situations safely, we propose to add a type Dynamic whose values are pairs of a value v and a type tag T where v has the type denoted by T. Instances of Dynamic are built with an explicit tagging construct and inspected with a type-safe typecase construct. This paper is an exploration of the syntax, operational semantics, and denotational semantics of a simple language with the type Dynamic. We give examples of how dynamically-typed values might be used in programming. Then we discuss an operational semantics for our language and obtain a soundness theorem. We present two formulations of the denotational semantics of this language and relate them to the operational semantics. Finally, we consider the implications of polymorphism and some implementation issues.
MECHANISMS OF ANGIOGENESISAND LYMPHANGIOGENESIS IN CALCIFIC AORTIC VALVE STENOSIS

Aortic valve stenosis (AVS) is the most common valvular disease in Western countries. Pharmacological prevention of AVS having proved unsuccessful, its current treatment is still valve replacement. The etiology of AVS is multifactorial, both genetic and external risk factors predisposing to the active pathological process eventually leading to clinically manifest stenosis. Histological features of the disease resemble those of atherosclerosis, including the accumulation and modification of lipoproteins, inflammation, extracellular matrix remodeling, and calcification. Furthermore, valvular interstitial cells undergo phenotypic differentiation into actively proliferating myofibroblasts, which contribute to the local inflammatory response as well as extracellular matrix remodeling in stenotic aortic valves. Blood vessels also grow into the normally avascular valve leaflets already in the early stages of the disease. This thesis aimed at elucidating the mechanisms behind the pathological neovascularization of the stenotic aortic valves. Furthermore, we characterized valvular lymphangiogenesis and investigated potential factors contributing to the balance between valvular angiogenesis and lymphangiogenesis, focusing on the role of valvular myofibroblasts and mast cells. For this purpose, we studied a total of 117 stenotic valves obtained at valve replacement surgery, and 49 control valves obtained at cardiac transplantations, at valve replacement surgery due to aortic valve regurgitation, or from deceased organ donors whose hearts were unsuitable for use as grafts. The valve leaflets were either used freshly for myofibroblast cell culture or frozen for e.g. PCR and immunohistochemical analyses. First, we assessed the adverse extracellular matrix remodeling of stenotic aortic valves, a process necessary for angiogenic sprouting to occur. We found that the mRNA expression levels of cathepsins S, K, and V, and their inhibitor cystatin C were higher in stenotic aortic valves than in control valves. Furthermore, the total activity of such cathepsins was increased in AVS. In immunohistochemical stainings, the expressions of cathepsin S, cathepsin V, and cystatin C localized to valvular macrophages, chondroblast-like cells, and endothelial cells lining both the valvular surface and the neovessels in the stenotic valves. Next, we characterized the neovessels and lymphatic vessels in stenotic aortic valves and control valves using immunohistochemistry. We found that in addition to immature microvessels, the stenotic aortic valves contained organized arterioles, indicating an advanced stage of angiogenesis. Lymphatic vessels correlated with valvular blood vessels, but were present in much fewer numbers. Valvular mast cells resided close to neovessels and secreted the angiogenic Vascular endothelial growth factor A (VEGF-A). Furthermore, we showed that the lymphangiogenic growth factors VEGF-C and VEGF-D are locally produced in the aortic valves, and that the receptors
A prospective cohort study on the short collum femoris-preserving (CFP) stem using RSA and DXA

Background and purpose Short femoral stems have been introduced in total hip arthroplasty in order to save proximal bone stock. We hypothesized that a short stem preserves periprosthetic bone mineral density (BMD) and provides good primary stability. Methods We carried out a prospective cohort study of 30 patients receiving the collum femoris-preserving (CFP) stem. Preoperative total hip BMD and postoperative periprosthetic BMD in Gruen zones 1–7 were investigated by dual-energy x-ray absorptiometry (DXA), stem migration was analyzed by radiostereometric analysis (RSA), and the Harris hip score (HHS) was determined. Results 2 patients were excluded intraoperatively and 1 patient was revised due to a deep infection, leaving 27 patients for analysis. The mean HHS increased from 49 (24–79) preoperatively to 99 (92–100) after 2 years. DXA after 1 year showed substantial loss of BMD in Gruen zone 7 (–31%), zone 6 (–19%), and zone 2 (–13%, p < 0.001) compared to baseline BMD determined immediately postoperatively. The bone loss in these regions did not recover after 2 years, whereas the more moderate bone loss in Gruen zones 1, 3, and 5 partially recovered. There was a correlation between low preoperative total hip BMD and a higher amount of bone loss in Gruen zones 2, 6 and 7. RSA showed minor micromotion of the stem: mean subsidence was 0.13 (95% CI: –0.28 to 0.01) mm and mean rotation around the longitudinal axis was 0.01º (95% CI: –0.1 to 0.39) after 2 years. Interpretation We conclude that substantial loss in proximal periprosthetic BMD cannot be prevented by the use of a novel type of short, curved stem, and forces appear to be transmitted distally. However, the stems showed very small migration—a characteristic of stable uncemented implants.
Response of maize to tillage and nitrogen management.

Best nitrogen management practices are the pre-requisite to warrant high maize yield. Thus, experiments were conducted to study the “effect of tillage and split application of nitrogen on hybrid maize” under semi-arid conditions of Pakistan, during fall 2008 and 2009. The experiments were laid out in randomized complete block design with split-plot arrangement, replicated three times in a net plot size of 4.5m x 10m at the Agronomic Research Area, University of Agriculture, Faisalabad. Three tillage treatments (conventional tillage (2-cultivation), tillage with mouldboard plough + 2-cultivation and tillage with chisel plough + 2-cultivation) were kept in main plots, while nitrogen application at different growth stages (Whole at sowing, 1⁄2 at sowing + 1⁄2 at V5 (5-leaf stage), 1⁄2 at sowing + 1⁄2 at tasseling, 1⁄2 at V5 + 1⁄2 at tasseling, /3 at sowing + /3 at V5 + /3 at tasseling) in sub-plots. Tillage methods improved the plant height, biomass yield, harvest index and shelling percentage during both the years while nitrogen application had no effect on plant height and harvest index but had significant effect on shelling percentage and biomass yield of maize. Chisel ploughed plots produced tallest plants, higher biomass, harvest index and shelling percentage while mould board plough resulted to shortest plants, lower biomass, harvest index and shelling percentage during both the years. Nitrogen application in three splits produced highest biomass yield and shelling percentage during 2008 and 2009. Variation in biomass yield in maize suggested temporal nitrogen management practices in maize grown by ploughing the soil with chisel plough followed by cultivator under semi-arid climatic conditions.