60 research outputs found
Steroid hormones and growth factors act in an integrated manner at the levels of hypothalamic astrocytes: a role in the neuroendocrine control of reproduction
No full textSeveral growth factors (e.g., transforming growth factors beta and alpha, basic fibroblast growth factor), produced by hypothalamic astrocytes, participate in the control of hypothalamic gonadotrophin-releasing hormone (GnRH) neurons. On this basis, we have hypothesized that steroid hormones, like estrogens and progestagens, influence the GnRH neurons by modulating in glial cells the synthesis and the release of these growth factors. Data reported here indicate that the expression of transforming growth factor beta 1 is modulated in hypothalamic astrocytes by a progesterone derivative (i.e., dihydroprogesterone), while estrogens modulate that of basic fibroblast growth factor. Moreover, it is interesting to highlight that the effect of estrogens on basic fibroblast growth factor is mediated by another growth factor (i.e., transforming growth factor alpha). Altogether, the present findings support the concept that steroid hormones and growth factors act in an integrated manner at the level of hypothalamic astrocytes, thus adding a further piece of knowledge in the understanding of the mechanisms controlling GnRH neurons
Noninvasive management of obstructing ureteral stones using electromagnetic extracorporeal shock wave lithotripsy (Surgical Endoscopy DOI: 10.1007/s00464-008-9766-6)
No full textExtending the velocity range of Robotic Volumetric PIV: Desing and application of a multi-Δt approach
No full textCar industry and motorsport development nowadays strongly rely on wind tunnel testing. As the literature survey shows, in order to fully understand the characteristics of the flow around a car, large-scale and volumetric flow field measurements are required. For its features, PIV can be pointed as a useful technique for automotive wind tunnels. However, its use in an automotive wind tunnel is strongly conditioned by the industrial environment itself, which requires particular efforts for what concerns safety and economic aspects.The advent of Robotic Volumetric PIV has permitted the measurement of time-averaged properties of large-scale complex aerodynamic flows by the combination of coaxial volumetric velocimetry and robotics. Firstly, the use of Helium Filled Soap Bubbles as seeding permits to enlarge the measurement volume due to their higher scattering capability. Furthermore, the compactness of the coaxial velocimetry probe together with the robotic actuation allows to measure large-scale volumes, partitioning the entire volume and reconstructing the time-averaged flow filed from multiple PIV acquisitions.Since its presentation, Robotic Volumetric PIV has been used to investigate low velocities flows, with free-stream values ranging between 2 m/s and 14 m/s. More specifically, 15 m/s can be considered the largest velocity that can be analysed with the state-of-the-art of the system due to its hardware limitations in the maximum acquisition frequency. For this reason, to meet the requirements in terms of flow velocities proper of industrial environments, the range of analysable velocities has to be extended. To address the identified requirement of high-speed volumetric measurements, a new acquisition technique has been designed and proposed. Even if a standard double-pulse strategy can measure high-speed flows due to the short time that can elapse between the two subsequent pulses, in order to increase the accuracy of the final results, a two- method is proposed. Firstly, a predictor is built using a Double-Pulse, Double-Frame acquisition with a short pulse separation time . Afterwards, the predictor is used to allow the stretching of the second pulse separation time without encountering errors given by the false pairing that would be present due to the longer displacement of the particles. To test the performance of the new method, the near wake of a replica of the Ahmed body with a 25 slant angle has been studied through an experimental campaign in the Open Jet Facility (OJF) of TU Delft. Firstly, a measurement at 12 m/s has been performed in order to be able to assess the performances of the proposed method w.r.t. the time-resolved acquisition strategy and the DP standard -DF approach. Afterwards, an airspeed of 20 m/s has been considered, in order to demonstrate the capability of the new technique of extending the velocity range of Robotic Volumetric PIV. The conducted measurements demonstrate the possibility of extending the velocity range of the Robotic Voluemtric PIV system with the proposed method. However, this is achieved at the expense of a lower accuracy, due to the lack of temporal information, and a longer measurement time, given by the necessity of multiple acquisitions.Aerospace Engineerin
Fibrosis and inflammation are greater in muscles of beta-sarcoglycan-null mouse than mdx mouse
No full textThe Sgcb-null mouse, with knocked-down β-sarcoglycan, develops severe muscular dystrophy as in type 2E human limb girdle muscular dystrophy. The mdx mouse, lacking dystrophin, is the most used model for Duchenne muscular dystrophy (DMD). Unlike DMD, the mdx mouse has mild clinical features and shows little fibrosis in limb muscles. To characterize ECM protein deposition and the progression of muscle fibrosis, we evaluated protein and transcript levels of collagens I, III and VI, decorin, and TGF-β1, in quadriceps and diaphragm, at 2, 4, 8, 12, 26, and 52 weeks in Sgcb-null mice, and protein levels at 12, 26, and 52 weeks in mdx mice. In Sgcb-null mice, severe morphological disruption was present from 4 weeks in both quadriceps and diaphragm, and included conspicuous deposition of extracellular matrix components. Histopathological features of Sgcb-null mouse muscles were similar to those of age-matched mdx muscles at all ages examined, but, in the Sgcb-null mouse, the extent of connective tissue deposition was generally greater than mdx. Furthermore, in the Sgcb-null mouse, the amount of all three collagen isoforms increased steadily, while, in the mdx, they remained stable. We also found that, at 12 weeks, macrophages were significantly more numerous in mildly inflamed areas of Sgcb-null quadriceps compared to mdx quadriceps (but not in highly inflamed regions), while, in the diaphragm, macrophages did not differ significantly between the two models, in either region. Osteopontin mRNA was also significantly greater at 12 weeks in laser-dissected highly inflamed areas of the Sgcb-null quadriceps compared to the mdx quadriceps. TGF-β1 was present in areas of degeneration-regeneration, but levels were highly variable and in general did not differ significantly between the two models and controls. The roles of the various subtypes of macrophages in muscle repair and fibrosis in the two models require further study. The Sgcb-null mouse, which develops early fibrosis in limb muscles, appears more promising than the mdx mouse for probing pathogenetic mechanisms of muscle fibrosis and for developing anti-fibrotic treatments. Highlights • The Sgcb-null mouse develops severe muscular dystrophy, the mdx mouse does not. • Fibrosis developed earlier in Sgcb-null quadriceps and diaphragm than mdx. • Macrophages were commoner in mildly inflamed parts of Sgcb-null quadriceps than mdx. • The Sgcb-null model appears more useful than mdx for studying fibrotic mechanisms. • The Sgcb-null model also appears more useful for developing anti-fibrotic treatments
Smad proteins are targets of transforming growth factor beta1 in immortalised gonadotrophin-releasing hormone releasing neurones
No full textTransforming growth factor beta (TGFbeta) is one of the growth factors involved in the neuroendocrine control of the gonadotrophin-releasing hormone (GnRH) neurones. It is produced and released by the astrocytes surrounding GnRH neurones and directly controls their secretory activity. TGFbeta signalling is based on a complex of two receptors that transduces the signal through peculiar intracellular substrates, the Smad proteins, which, upon activation, move into the nucleus, and modify the transcription of TGFbeta responsive genes. The present study aimed to verify whether TGFbeta1 is able to regulate the Smad pathway in GT1-1 cells (i.e. an immortalised neuronal cell line releasing GnRH). We show that: (i) GT1-1 cells express Smad 2, 3, 4, and 7; (ii) TGFbeta1 enhances the phosphorylation of Smad 2 and 3 at short times of exposure (15-30 min); (iii) TGFbeta1 induces the synthesis of the inhibitory Smad 7 at longer times (60-120-240 min); (iv) the conditioned medium of type 1 astrocytes enhances the phosphorylation of Smad 2 and 3 in GT1-1 cells and a TGFbeta1 neutralising antibody counteracts this effect. The results indicate that Smads are targets of TGFbeta1 and that astrocytes are able to modulate Smads proteins in GT1-1 cells through the release of TGFbeta1. Taken together, the data provide new evidence that glial cells are important regulators of the GnRH neuronal activity
Myopathic changes associated with psychomotor delay and seizures caused by a novel homozygous mutation in TBCK
No full textBackground: Biallelic mutations in TBC1-domain containing kinase (TBCK) lead to hypotonia, global developmental delay with severe cognitive and motor deficits, and variable presentation of dysmorphic facial features and brain malformations. It remains unclear whether hypotonia in these individuals is purely neurogenic, or also caused by progressive muscle disease. Methods: Whole exome sequencing was performed on a family diagnosed with nonspecific myopathic changes by means of histological analysis and immunohistochemistry of muscle biopsy samples. Results: A novel homozygous truncation in TBCK was found in two sisters diagnosed with muscle disease and severe psychomotor delay. TBCK was completely absent in these patients. Conclusions: Our findings identify a novel early truncating variant in TBCK associated with a severe presentation and add muscle disease to the variability of phenotypes associated with TBCK mutations. Inconsistent genotype/phenotype correlation could be ascribed to the multiple roles of TBCK in intracellular signaling and endolysosomal function in different tissues
Advancements in Large-Scale Volumetric PIV and PTV
No full textParticle Image Velocimetry (PIV) is considered nowadays the state-of-the-art for non-intrusive and quantitative 3D velocity measurements. Its ability to measure the velocity field around complex geometries is a valuable tool that engineers can exploit for aerodynamic design optimization in various domains, such as aerospace, wind turbines and automotive, among others. Despite recent advancements, performing a PIV measurement in the industrial environment remains challenging due to several reasons: achieving large-scale measurements, complex geometries and high Reynolds numbers. The introduction of helium-filled soap bubbles, new Lagrangian Particle Tracking (LPT) algorithms and Robotic Volumetric PIV has allowed for the measurement of large-scale volumes around complex geometries. However, despite the described advancements, large-scale PIV and LPT measurements for industrial aerodynamics require further development to accelerate their applications. The first bottleneck considered is the maximum measurable velocity. For aerodynamic flows in the transport sector, the velocity is often larger than 50 m/s when considering aircraft and race cars. To apply the mentioned techniques, acquisition frequencies higher than the one commonly available are needed. The double-frame timing strategy, characterized by image pairs with a small time separation, is detrimental to the measurement accuracy, especially when low aperture systems, such as Robotic Volumetric PIV, are considered. This research has led to the development of novel acquisition strategies (chapters 3 and 4) that improve the accuracy of double-frame velocity measurements suited for high speed applications (U∞ > 50 m/s). Another current topic of research concerns the detection of data outliers in PIV measurements, which affect their reliability and trustfulness. In this thesis (chapter 5) a novel approach to outliers detection from time-averaged three dimensional PIV data is introduced. The principle invokes the physical mechanism of turbulence transport and is based on the agreement of the measured data to the turbulent kinetic energy (TKE) transport equation. The application of this new criterium to several experimental databases shows that spurious data can be detected more easily and unambiguously as an outlier along with a low fraction of false positives. This research also attempts to decrease the gap between Computational Fluid Dynamics’ (CFD) and experiments’ aerodynamic data. In chapter 6, the application of PIV data for data assimilation is discussed. Data assimilation is a discipline in which observation and numerical or theoretical models are combined. This can be performed with two possible aims: improving the observation with physics-based models or increasing the capability of the model to represent reality. In this thesis, the latter is considered. A novel state observer technique is investigated for the assimilation of three-dimensional velocity measurements into computational fluid dynamics simulations based on Reynolds-averaged Navier–Stokes (RANS) equations. The state observer approach locally forces the solution to comply with the reference value, with increasing benefits when the density of forced points, or forcing density, is increased.Aerodynamic
Assessment of neuroactive steroid formation in diabetic rat spinal cord using high-performance liquid chromatography and continuous flow scintillation detection
No full textThe combination of pulse-chase experiments with high-performance liquid chromatography and continuous flow scintillation detection was
used successfully to determine the effects of chronic diabetes on neurosteroid production in the adult rat spinal cord. The long-term diabetes was
induced by treatment of adult rats with streptozotocin. In the first part, the review provides an extensive description of the HPLC combined with
continuous flow scintillation detection method, its advantages and appropriateness for the question investigated. Afterwards, the paper shows that
progesterone formation is up-regulated in the spinal cord of diabetic rats while the biosynthesis of tetrahydroprogesterone decreased. The downregulation
of tetrahydroprogesterone appeared as a mechanism facilitating progesterone accumulation in the spinal cord of streptozotocin-treated
rats. Progesterone is well known to be a potent neuroprotective steroid. Enhancement of its biosynthesis may be an endogenous mechanism
triggered by neural cells in the spinal tissue to cope with degenerative effects provoked by chronic diabetes. Since steroid metabolism in the spinal
cord is pivotal for the modulation of several neurobiological processes including sensorimotor activities, the data analyzed herein may constitute
useful information for the development of efficient strategies against deleterious effects of diabetes on the nervous system
Familial adult-onset Pompe disease associated with unusual clinical and histological features.
No full textThe adult-onset form of Pompe disease had a wide clinical spectrum, ranging from asymptomatic patients with increased CK to muscle cramps and pain syndrome or rigid-spine syndrome. In addition clinical severity and disease progression are greatly variable. We report on a family with 3 siblings characterized by an unusual adult-onset Pompe disease including dysphagia and weakness of tongue, axial and limb-girdle muscles, in association with atypical globular inclusions in muscle fibres. Our study confirms the great clinical and histological variability of adult-onset Pompe disease and further supports the need of careful evaluation of bulbar function in patients affected by this pathology
Cardiovascular Risk Predicts White Matter Hyperintensities, Brain Atrophy and Treatment Resistance in Major Depressive Disorder: Role of Genetic Liability
No full textIntroduction: Depressive disorders are a leading cause of global disease burden, particularly with the challenge of treatment-resistant depression (TRD). Research points to a complex bidirectional relationship between cardiovascular (CV) risk factors and TRD, with CV risk negatively impacting brain structure and potentially influencing antidepressant resistance. Moreover, the association between depression and the genetic vulnerability to cardiovascular disease suggests a shared pathophysiological process between the two. This study investigates the mediating role of brain structural alterations in the relationship between CV and cerebrovascular (CeV) risk and treatment resistance in depression. Methods: We assessed 165 inpatients with Major depressive disorder. Each patient's CV risk was assessed via the QRISK 3 calculator. For a subset of patients, CV and CeV disease polygenic risk scores (PRS) were obtained. All patients underwent a 3 T MRI scan, and white matter hyperintensities estimates and indicators of brain trophic state were obtained. Results: Both CV risk and CV disease PRSs are associated with treatment resistance status, white matter hyperintensities, and indicators of brain atrophy. Mediation analyses suggested that CV-induced brain alterations might underlie the relation between CV genetic and phenotypic risk and antidepressant treatment resistance. Conclusion: These results underscore the need to explore cardiovascular risk management as part of treatment strategies for depression, pointing toward a shared pathophysiological process linking heart and brain health in treatment-resistant depression
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