Statistical modeling of atmospheric turbulence based on a low-cost experimental setup for measuring C n2 over water.

The performance of communication systems based on free-space optical links depends on external factors such as weather conditions. Among many atmospheric factors, turbulence can be the greatest challenge to performance. The characterization of atmospheric turbulence usually involves expensive equipment known as a scintillometer. This work presents a low-cost experimental setup for measuring the refractive index structure constant over water, which results in a statistical model based on weather conditions. The turbulence variations with air and water temperature, relative humidity, pressure, dew point, and different watercourse widths are analyzed for the proposed scenario.

A Novel Route to Optimize Placement Equipment Kinematics by Coupling Capacitive Accelerometers.

Machine end-effector kinematic analysis is critical to optimizing transporting components where inertial forces are the main loads. While displacements may be measured with relatively high accuracy in transportation equipment motors, the inertial forces in the transported components are seldom optimized. This is especially relevant in electronic component placement systems, where the components have a wide range of configurations (i.e., geometry and mass) and the deployment dimensional/geometric tolerances are remarkably good. The optimization of these systems requires the monitoring of the real position of the accelerometers relative to the measurement point of interest with sufficient accuracy that allows the assembly position to be predicted instantaneously. This study shows a novel method to calibrate this equipment using triaxial accelerometers on a surface mount machine to measure the end-effector accelerations and velocities in its planar motion. The dynamic equations of the system and the method for integration are presented to address the uncertainty on the exact position of the accelerometer sensors relative to the measuring point of interest exist and allow the position correction to optimize response and accuracy.

Ecological plasticity and commercial impact of invasive marbled crayfish populations in Madagascar.

BACKGROUND: The marbled crayfish (Procambarus virginalis) is a monoclonal, parthenogenetically reproducing freshwater crayfish species that has formed multiple stable populations worldwide. Madagascar hosts a particularly large and rapidly expanding colony of marbled crayfish in a unique environment characterized by a very high degree of ecological diversity. RESULTS: Here we provide a detailed characterization of five marbled crayfish populations in Madagascar and their habitats. Our data show that the animals can tolerate a wide range of ecological parameters, consistent with their invasive potential. While we detected marbled crayfish in sympatry with endemic crayfish species, we found no evidence for the transmission of the crayfish plague pathogen, a potentially devastating oomycete. Furthermore, our results also suggest that marbled crayfish are active predators of the freshwater snails that function as intermediate hosts for human schistosomiasis. Finally, we document fishing, farming and market sales of marbled crayfish in Madagascar. CONCLUSIONS: Our results provide a paradigm for the complex network of factors that promotes the invasive spread of marbled crayfish. The commercial value of the animals is likely to result in further anthropogenic distribution.

Resveratrol Reverses Functional Chagas Heart Disease in Mice.

Chronic chagasic cardiomyopathy (CCC) develops years after acute infection by Trypanosoma cruzi and does not improve after trypanocidal therapy, despite reduction of parasite burden. During disease, the heart undergoes oxidative stress, a potential causative factor for arrhythmias and contractile dysfunction. Here we tested whether antioxidants/ cardioprotective drugs could improve cardiac function in established Chagas heart disease. We chose a model that resembles B1-B2 stage of human CCC, treated mice with resveratrol and performed electrocardiography and echocardiography studies. Resveratrol reduced the prolonged PR and QTc intervals, increased heart rates and reversed sinus arrhythmia, atrial and atrioventricular conduction disorders; restored a normal left ventricular ejection fraction, improved stroke volume and cardiac output. Resveratrol activated the AMPK-pathway and reduced both ROS production and heart parasite burden, without interfering with vascularization or myocarditis intensity. Resveratrol was even capable of improving heart function of infected mice when treatment was started late after infection, while trypanocidal drug benznidazole failed. We attempted to mimic resveratrol's actions using metformin (AMPK-activator) or tempol (SOD-mimetic). Metformin and tempol mimicked the beneficial effects of resveratrol on heart function and decreased lipid peroxidation, but did not alter parasite burden. These results indicate that AMPK activation and ROS neutralization are key strategies to induce tolerance to Chagas heart disease. Despite all tissue damage observed in established Chagas heart disease, we found that a physiological dysfunction can still be reversed by treatment with resveratrol, metformin and tempol, resulting in improved heart function and representing a starting point to develop innovative therapies in CCC.

Epigenetic changes modulate schistosome egg formation and are a novel target for reducing transmission of schistosomiasis.

Treatment and control of schistosomiasis relies on the only available drug, praziquantel, and the search for alternative chemotherapeutic agents is therefore urgent. Egg production is required for the transmission and immunopathology of schistosomiasis and females of S. mansoni lay 300 eggs daily. A large fraction of the total mRNA in the mature female worm encodes one eggshell protein, Smp14. We report that the nuclear receptors SmRXR1 and SmNR1 regulate Smp14 transcription through the recruitment of two histone acetyltransferases (HATs), SmGCN5 and SmCBP1. The treatment of HEK293 cells with histone deacetylase (HDAC) inhibitors (NaB or TSA) produced an 8-fold activation of the SmRXR1/SmNR1-mediated Smp14 promoter activity. Incubation with synthetic HAT inhibitors, including PU139, significantly impaired the Smp14 promoter activity in these cells. Worm pairs cultivated in the presence of PU139 exhibited limited expression of Smp14 mRNA and protein. ChIP analysis demonstrated chromatin condensation at the Smp14 promoter site in worms treated with PU139. ChIP also revealed the presence of H3K27me3 and the absence of RNA Pol II at the Smp14 promoter region in the PU139-treated worms. Most significantly, the PU139-mediated inhibition of Smp14 expression resulted in a significant number of abnormal eggs as well as defective eggs within the ootype. In addition, scanning electron microscopy revealed structural defects and unformed eggshells, and vitelline cell leakage was apparent. The dsRNAi-targeting of SmGCN5 or SmCBP1 significantly decreased Smp14 transcription and protein synthesis, which compromised the reproductive system of mature female worms, egg-laying and egg morphology. Our data strongly suggest that the inhibition of Smp14 expression targeting SmGCN5 and/or SmCBP1 represents a novel and effective strategy to control S. mansoni egg development.

A Comparative Thermoacoustic Insulation Study of Silica Aerogels Reinforced with Reclaimed Textile Fibres: Cotton, Polyester and Wool.

Silica aerogels are highly porous materials with exceptional thermal insulation performance. They become even more attractive if combined thermal and acoustic insulation is achieved. Silica aerogel composites reinforced with fibres are an ingenious way to surpass the fragility stemmed from the aerogel's intrinsic porosity, and textile fibres are good sound absorption materials. Reclaimed fibres are a relatively low-cost feedstock and were obtained in this work exclusively through mechanical processes from textile wastes, thus promoting the concept of circular economy, namely for cotton, polyester and wool fibres. These reclaimed fibres were used as reinforcement matrices for silica aerogel composites obtained from sol-gel transformation of tetraethyl orthosilicate and isobutyltriethoxysilane/or vinyltrimethoxysilane precursors and dried at ambient pressure after silylation. Silica aerogel composites reinforced with reclaimed cotton fibres had the best sound absorption coefficient (a peak value of 0.89), while the polyester-reinforced composite exhibited the lowest thermal conductivity (k = ~24 mW m-1 K-1, Hot Disk). The better combined results on thermal and acoustic insulation were achieved by the wool-reinforced composites. The thermal conductivity values were less than 27 mW m-1 K-1, and the sound absorption coefficient achieved a peak value of 0.85. Therefore, the aerogel composites developed here can be selected for thermal or/and acoustic barriers by choosing a suitable type of fibre. Their design and preparation protocol followed environmental-friendly and cost-effective approaches.

Reinvestigating the clinical relevance of the m6A writer METTL3 in urothelial carcinoma of the bladder.

METTL3 is the major writer of N6-Methyladenosine (m6A) and has been associated with controversial roles in cancer. This is best illustrated in urothelial carcinoma of the bladder (UCB), where METTL3 was described to have both oncogenic and tumor-suppressive functions. Here, we reinvestigated the role of METTL3 in UCB. METTL3 knockout reduced the oncogenic phenotype and m6A levels of UCB cell lines. However, complete depletion of METTL3/m6A was not achieved due to selection of cells expressing alternative METTL3 isoforms. Systematic vulnerability and inhibitor response analyses suggested that uroepithelial cells depend on METTL3 for viability. Furthermore, expression and survival analyses of clinical data revealed a complex role for METTL3 in UCB, with decreased m6A mRNA levels in UCB tumors. Our results suggest that METTL3 expression may be a suitable diagnostic UCB biomarker, as the enzyme promotes UCB formation. However, the suitability of the enzyme as a therapeutic target should be evaluated carefully.

ICI 182,780 induces P-cadherin overexpression in breast cancer cells through chromatin remodelling at the promoter level: a role for C/EBPbeta in CDH3 gene activation.

CDH3/P-cadherin is a classical cadherin. Overexpression of which has been associated with proliferative lesions of high histological grade, decreased cell polarity and poor survival of patients with breast cancer. In vitro studies showed that it can be up-regulated by ICI 182,780, suggesting that the lack of ERalpha signalling is responsible for the aberrant P-cadherin overexpression and for its role in inducing breast cancer cell invasion and migration. However, the mechanism by which ER-signalling inhibition leads to P-cadherin expression is still unknown. The aim of this study was to explore the molecular mechanism linking the ERalpha-signalling and P-cadherin-regulated expression in breast cancer cell lines. This study showed that ICI 182,780 is able to increase CDH3 promoter activity, inducing high levels of the active chromatin mark H3 lysine 4 dimethylation. We also observed, for the first time, that the transcription factor C/EBPbeta is able to up-regulate CDH3 promoter activity in breast cancer cells. Moreover, we showed that the expression of P-cadherin and C/EBPbeta are highly associated in human breast carcinomas and linked with a worse prognosis of breast cancer patients. This study demonstrates the existence of an epigenetic regulation by which ICI 182,780 up-regulates P-cadherin expression in MCF-7/AZ breast cancer cells through chromatin remodelling at CDH3 promoter, bringing forward the growing evidence that ERalpha signalling-abrogation by anti-oestrogens is able to induce the expression of ERalpha-repressed genes which, in the appropriate cell biology context, may contribute to a breast cancer cell invasion phenotype.CDH3 GenBank accession no. NT_010498.

Cystic lymphangioma of the pancreatic head treated by enucleation: Case report and literature review.

INTRODUCTION: The widespread use of imaging methods has led to an increased identification of asymptomatic Pancreatic Cystic Lymphangiomas (PCL), a rare entity for which available information is very limited. PRESENTATION OF CASE: We present the case of an asymptomatic 61-year-old male, submitted to elective enucleation of a pancreatic head PCL at our institution. After four years of follow-up the patient is doing well and has no clinical or imaging signs of recurrence. DISCUSSION: Though rare, PCL should be included in the differential diagnosis of pancreatic cystic neoplasms. All efforts should be made to ascertain a preoperative diagnosis, as expectant follow-up could be a reasonable approach in asymptomatic patients and/or poor surgical candidates. In the face of an uncertain diagnosis, complete surgical excision may be the treatment of choice. CONCLUSION: The medical community worldwide should be encouraged to report all cases of PCL, as to increment the overall knowledge about this lesion.

Extramedullary Acute Leukemia-Still an Unforeseen Presentation.

Myeloid sarcomas (MS) are rare extramedullary (EM) hematological tumors that generally arise during the natural course of acute myeloid leukemia (AML), occurring concomitantly with the onset of systemic leukemia; it can also occur following onset but rarely before. Common sites of EM involvement include the lymph nodes, skin, soft tissue, bone and peritoneum. Herein, we report the case of a 63-year-old man who presented EM AML upon initial diagnosis involving the bone marrow, lymph nodes and skin (leukemia cutis). A diagnosis was made based on immunohistochemistry (IHC). This case presents a diagnostic dilemma due to its atypical presentation and the sites involved. It also highlights the importance of IHC in the diagnosis of EM AML. The potential role of hypomethylating agents and Venetoclax in cases not eligible for hematopoietic stem cell transplant are also discussed.

Zika virus infection drives epigenetic modulation of immunity by the histone acetyltransferase CBP of Aedes aegypti.

Epigenetic mechanisms are responsible for a wide range of biological phenomena in insects, controlling embryonic development, growth, aging and nutrition. Despite this, the role of epigenetics in shaping insect-pathogen interactions has received little attention. Gene expression in eukaryotes is regulated by histone acetylation/deacetylation, an epigenetic process mediated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, we explored the role of the Aedes aegypti histone acetyltransferase CBP (AaCBP) after infection with Zika virus (ZIKV), focusing on the two main immune tissues, the midgut and fat body. We showed that the expression and activity of AaCBP could be positively modulated by blood meal and ZIKV infection. Nevertheless, Zika-infected mosquitoes that were silenced for AaCBP revealed a significant reduction in the acetylation of H3K27 (CBP target marker), followed by downmodulation of the expression of immune genes, higher titers of ZIKV and lower survival rates. Importantly, in Zika-infected mosquitoes that were treated with sodium butyrate, a histone deacetylase inhibitor, their capacity to fight virus infection was rescued. Our data point to a direct correlation among histone hyperacetylation by AaCBP, upregulation of antimicrobial peptide genes and increased survival of Zika-infected-A. aegypti.

Nottingham Prognostic Index in triple-negative breast cancer: a reliable prognostic tool?

BACKGROUND: A breast cancer prognostic tool should ideally be applicable to all types of invasive breast lesions. A number of studies have shown histopathological grade to be an independent prognostic factor in breast cancer, adding prognostic power to nodal stage and tumour size. The Nottingham Prognostic Index has been shown to accurately predict patient outcome in stratified groups with a follow-up period of 15 years after primary diagnosis of breast cancer. Clinically, breast tumours that lack the expression of Oestrogen Receptor, Progesterone Receptor and Human Epidermal growth factor Receptor 2 (HER2) are identified as presenting a "triple-negative" phenotype or as triple-negative breast cancers. These poor outcome tumours represent an easily recognisable prognostic group of breast cancer with aggressive behaviour that currently lack the benefit of available systemic therapy. There are conflicting results on the prevalence of lymph node metastasis at the time of diagnosis in triple-negative breast cancer patients but it is currently accepted that triple-negative breast cancer does not metastasize to axillary nodes and bones as frequently as the non-triple-negative carcinomas, favouring instead, a preferentially haematogenous spread. Hypothetically, this particular tumour dissemination pattern would impair the reliability of using Nottingham Prognostic Index as a tool for triple-negative breast cancer prognostication. METHODS: The present study tested the effectiveness of the Nottingham Prognostic Index in stratifying breast cancer patients of different subtypes with special emphasis in a triple-negative breast cancer patient subset versus non- triple-negative breast cancer. RESULTS: We demonstrated that besides the fact that TNBC disseminate to axillary lymph nodes as frequently as luminal or HER2 tumours, we also showed that TNBC are larger in size compared with other subtypes and almost all grade 3. Additionally, survival curves demonstrated that these prognostic factors are equally important to stratify different survival outcomes in non-TNBC as in TNBC. We also showed that the NPI retains the ability to stratify and predict survival of TNBC patients. CONCLUSION: The importance of this study relies on the need of prognostication improvements on TNBC, showing, at a clinical standpoint, that Nottingham Prognostic Index is as a truthful prognostic tool in TNBC.

Enucleation of a giant symptomatic gastric lipoma, a safe surgical approach.

Gastric lipomas are rare, representing 2-3% of all benign tumours of the stomach. Most of these stomach neoplasms are small and detected incidentally during endoscopic or radiology evaluations. Computed tomography is highly specific imaging for lipoma diagnosis. Endoscopy and endoscopic ultrasound are other important diagnostic modalities to confirm the diagnosis. Identifying typical features can avoid biopsy or surgery in asymptomatic patients. In patients with larger lesions, usually more than 2 cm, clinical presentation may encompass haemorrhage, abdominal pain, pyloric obstruction and dyspepsia. As a result of its extreme low incidence, treatment is not standardized, though it is widely accepted that a symptomatic tumour mandates resection. Here, we present the case of a 60-year-old female presenting with abdominal pain and recurrent vomiting due to a giant gastric lipoma (80 × 35 × 35 mm). The patient underwent laparotomy and an enucleation was performed.

Location-Dependent DNA Methylation Signatures in a Clonal Invasive Crayfish.

DNA methylation is an important epigenetic modification that has been repeatedly implied in organismal adaptation. However, many previous studies that have linked DNA methylation patterns to environmental parameters have been limited by confounding factors, such as cell-type heterogeneity and genetic variation. In this study, we analyzed DNA methylation variation in marbled crayfish, a clonal and invasive freshwater crayfish that is characterized by a largely tissue-invariant methylome and negligible genetic variation. Using a capture-based subgenome bisulfite sequencing approach that covers a small, variably methylated portion of the marbled crayfish genome, we identified specific and highly localized DNA methylation signatures for specimens from geographically and ecologically distinct wild populations. These results were replicated both biologically and technically by re-sampling at different time points and by using independent methodology. Finally, we show specific methylation signatures for laboratory animals and for laboratory animals that were reared at a lower temperature. Our results thus demonstrate the existence of context-dependent DNA methylation signatures in a clonal animal.

Rapid Epigenetic Adaptation in Animals and Its Role in Invasiveness.

Invasive species represent a serious ecological threat for many ecosystems worldwide and provide a unique opportunity to investigate rapid adaptation and evolution. Genetic variation allows populations of organisms to be both robust and adaptable to different environmental conditions over evolutionary timeframes. In contrast, invasive animals can rapidly adapt to new environments, with minimal genetic diversity. Thus, the extent to which environmental effects can trigger epigenetic responses is particularly interesting for understanding the role of epigenetics in rapid adaptation. In this review, we provide a brief overview of the different epigenetic mechanisms that control gene expression, and emphasize the importance of epigenetics for environmental adaptation. We also discuss recent publications that provide important examples for the role of epigenetic mechanisms in environmental adaptation. Furthermore, we present an overview of the current knowledge about epigenetic modulation as an adaptive strategy for invasive species. A particularly interesting example is provided by the marbled crayfish, a novel, monoclonal freshwater crayfish species that has colonized diverse habitats within a few years. Finally, we address important limitations of current approaches and highlight the potential importance of less well-known mechanisms for non-genetic organismal adaptation.

Heterotopic gastric mucosa in the gallbladder-a rare find.

It is universally known and accepted that the development of a certain type of tissue outside its usual location, like in the gastrointestinal tract, can occur. This is a relatively common situation in the upper region of the gastrointestinal tract. However, the development of gastric mucosa in the gallbladder is a rare find. The following is the case of a 22-year-old male with an 18 mm gallbladder polyp, who electively underwent a laparoscopic cholecystectomy, having been diagnosed at a histopathological level with heterotopic gastric mucosa in the gallbladder. This brief article also aims to provide a reflection on the possible evolution of neoplasms from this histological change, based on the doubts raised in literature.

A rare tumour, a singular indication: sleeve gastrectomy in a morbidly obese septuagenarian with gastric schwannoma.

Gastric schwannoma is an extremely rare mesenchymal tumour, representing only 0.2% of all gastric tumours. Obesity is an alarming worldwide disease whose only effective and sustained treatment seems to be surgical. We present a case of a 73-year-old female with epigastric pain and unspecific dyspeptic symptoms, whose diagnostic endoscopic procedures raised suspicion of a gastrointestinal stromal tumour. Given her good performance status, and since grade 2 obesity with high-risk comorbid conditions was present, she was considered a suitable candidate for laparoscopic sleeve gastrectomy. Both surgery and immediate postoperative period were uneventful. Histological and immunocytochemical analysis classified the tumour as benign gastric schwannoma. After 24 months, besides being disease-free, she presented an excess weight loss of 90.2%, with improvements in metabolic profile allowing withdrawal from chronic medication. The patient is healthier, satisfied and living an active life, showing that age by itself should not be a deterrent to bariatric surgery.

Pharmacological inhibition of lysine-specific demethylase 1 (LSD1) induces global transcriptional deregulation and ultrastructural alterations that impair viability in Schistosoma mansoni.

Treatment and control of schistosomiasis still rely on only one effective drug, praziquantel (PZQ) and, due to mass treatment, the increasing risk of selecting for schistosome strains that are resistant to PZQ has alerted investigators to the urgent need to develop novel therapeutic strategies. The histone-modifying enzymes (HMEs) represent promising targets for the development of epigenetic drugs against Schistosoma mansoni. In the present study, we targeted the S. mansoni lysine-specific demethylase 1 (SmLSD1), a transcriptional corepressor, using a novel and selective synthetic inhibitor, MC3935, which was used to treat schistosomula and adult worms in vitro. By using cell viability assays and optical and electron microscopy, we showed that treatment with MC3935 affected parasite motility, egg-laying, tegument, and cellular organelle structures, culminating in the death of schistosomula and adult worms. In silico molecular modeling and docking analysis suggested that MC3935 binds to the catalytic pocket of SmLSD1. Western blot analysis revealed that MC3935 inhibited SmLSD1 demethylation activity of H3K4me1/2. Knockdown of SmLSD1 by RNAi recapitulated MC3935 phenotypes in adult worms. RNA-Seq analysis of MC3935-treated parasites revealed significant differences in gene expression related to critical biological processes. Collectively, our findings show that SmLSD1 is a promising drug target for the treatment of schistosomiasis and strongly support the further development and in vivo testing of selective schistosome LSD1 inhibitors.

Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours.

INTRODUCTION: The expression of additional genes, other than oestrogen receptor (ER), may be important to the hormone-responsive phenotype of breast cancer. Microarray analyses have revealed that forkhead box A1 (FOXA1) and GATA binding protein 3 (GATA-3) are expressed in close association with ERalpha, both encoding for transcription factors with a potential involvement in the ERalpha-mediated action in breast cancer. The purpose of this study was to explore if the expression of FOXA1 and GATA-3 may provide an opportunity to stratify subsets of patients that could have better outcome, among the ERalpha-negative/poor prognosis breast cancer group. METHODS: We evaluate FOXA1 and GATA-3 expression in 249 breast carcinomas by immunohistochemistry, associating it with breast cancer molecular markers, clinicopathological features and patient's survival. The clinicopathological features and immunohistochemical markers of the tumours were compared using the chi-square test and ANOVA. Disease-free survival was analysed through Kaplan-Meier survival curves and Cox regression. RESULTS: FOXA1 expression was demonstrated in 42% of invasive carcinomas, while GATA-3 was detected in 48% of the cases. FOXA1 expression was inversely associated with tumour size, Nottingham Prognostic Index, histological grade, lymph vascular invasion, lymph node stage and human epidermal growth factor receptor-2 (HER-2) overexpression, while GATA-3 expression showed inverse association with histological grade and HER-2. Both FOXA1 and GATA-3 were directly associated with ERalpha and progesterone receptor. Among FOXA1-positive tumours, 83.1% are comprised in the luminal A subtype, similar to GATA-3 where 87.7% of positive tumours were classified within this molecular subtype. In the subset of ERalpha-negative patients, those who were FOXA1-negative had a 3.61-fold increased risk of breast cancer recurrence when compared with the FOXA1-positive. CONCLUSIONS: FOXA1 was a significant predictor of good outcome in breast cancer, whereas GATA-3 was an important luminal marker. The expression of FOXA1 may be used for risk stratification among ERalpha-negative patients.

The extracellular release of Schistosoma mansoni HMGB1 nuclear protein is mediated by acetylation.

Schistosoma mansoni HMGB1 (SmHMGB1) was revealed to be a substrate for the parasite histone acetyltransferases SmGCN5 and SmCBP1. We found that full-length SmHMGB1, as well as its HMG-box B (but not HMG-box A) were acetylated in vitro by SmGCN5 and SmCBP1. However, SmCBP1 was able to acetylate both substrates more efficiently than SmGCN5. Interestingly, the removal of the C-terminal acidic tail of SmHMGB1 (SmHMGB1DeltaC) resulted in increased acetylation of the protein. We showed by mammalian cell transfection assays that SmHMGB1 and SmHMGB1DeltaC were transported from the nucleus to the cytoplasm after sodium butyrate (NaB) treatment. Importantly, after NaB treatment, SmHMGB1 was also present outside the cell. Together, our data suggest that acetylation of SmHMGB1 plays a role in cellular trafficking, culminating with its secretion to the extracellular milieu. The possible role of SmHMGB1 acetylation in the pathogenesis of schistosomiasis is discussed.