Neurofilaments in motor neuron disorders: towards promising diagnostic and prognostic biomarkers

Motor neuron diseases (MNDs) are etiologically and biologically heterogeneous diseases. The pathobiology of motor neuron degeneration is still largely unknown, and no effective therapy is available. Heterogeneity and lack of specific disease biomarkers have been appointed as leading reasons for past clinical trial failure, and biomarker discovery is pivotal in today’s MND research agenda. In the last decade, neurofilaments (NFs) have emerged as promising biomarkers for the clinical assessment of neurodegeneration. NFs are scaffolding proteins with predominant structural functions contributing to the axonal cytoskeleton of myelinated axons. NFs are released in CSF and peripheral blood as a consequence of axonal degeneration, irrespective of the primary causal event. Due to the current availability of highly-sensitive automated technologies capable of precisely quantify proteins in biofluids in the femtomolar range, it is now possible to reliably measure NFs not only in CSF but also in blood. In this review, we will discuss how NFs are impacting research and clinical management in ALS and other MNDs. Besides contributing to the diagnosis at early stages by differentiating between MNDs with different clinical evolution and severity, NFs may provide a useful tool for the early enrolment of patients in clinical trials. Due to their stability across the disease, NFs convey prognostic information and, on a larger scale, help to stratify patients in homogenous groups. Shortcomings of NFs assessment in biofluids will also be discussed according to the available literature in the attempt to predict the most appropriate use of the biomarker in the MND clinic

Yangians, finite W-algebras and the Non Linear Schrodinger hierarchy

We show an algebra morphism between Yangians and some finite W-algebras. This correspondence is nicely illustrated in the framework of the Non Linear Schrodinger hierarchy. For such a purpose, we give an explicit realization of the Yangian generators in terms of deformed oscillators.Comment: LaTeX2e, 10 pages, Talk presented by E. Ragoucy at ACTP-Nankai Symposium on Yang-Baxter systems, non linear models and their applications, Seoul (Korea) October 20-23, 199

Inhibition of cell proliferation, migration and invasion of B16-F10 melanoma cells by α-mangostin

In this study, we have evaluated the potential antineoplastic effects of α-mangostin (α-M), the most representative xanthone in Garcinia mangostana pericarp, on melanoma cell lines. This xanthone markedly inhibits the proliferation of high-metastatic B16-F10 melanoma cells. Furthermore, by deeply analyzing which steps in the metastatic process are influenced by xanthone it was observed that α-M strongly interferes with homotypic aggregation, adhesion, plasticity and invasion ability of B16-F10 cells, probably by the observed reduction of metalloproteinase-9 activity. The antiproliferative and antimetastatic properties of α-M have been established in human SK-MEL-28 and A375 melanoma cells. In order to identify pathways potentially involved in the antineoplastic properties of α-M, a comparative mass spectrometry proteomic approach was employed. These findings may improve our understanding of the molecular mechanisms underlying the anti-cancer effects of α-M on melanoma

Quantum States of Topologically Massive Electrodynamics and Gravity

The free quantum states of topologically massive electrodynamics and gravity in 2+1 dimensions, are explicitly found. It is shown that in both theories the states are described by infrared-regular polarization tensors containing a regularization phase which depends on the spin. This is done by explicitly realizing the quantum algebra on a functional Hilbert space and by finding the Wightman function to define the scalar product on such a Hilbert space. The physical properties of the states are analyzed defining creation and annihilation operators. For both theories, a canonical and covariant quantization procedure is developed. The higher order derivatives in the gravitational lagrangian are treated by means of a preliminary Dirac procedure. The closure of the Poincar\'e algebra is guaranteed by the infrared-finiteness of the states which is related to the spin of the excitations through the regularization phase. Such a phase may have interesting physical consequences.Comment: 21 page, latex, no figure

Probing quantum coherence in qubit arrays

We discuss how the observation of population localization effects in periodically driven systems can be used to quantify the presence of quantum coherence in interacting qubit arrays. Essential for our proposal is the fact that these localization effects persist beyond tight-binding Hamiltonian models. This result is of special practical relevance in those situations where direct system probing using tomographic schemes becomes infeasible beyond a very small number of qubits. As a proof of principle, we study analytically a Hamiltonian system consisting of a chain of superconducting flux qubits under the effect of a periodic driving. We provide extensive numerical support of our results in the simple case of a two-qubits chain. For this system we also study the robustness of the scheme against different types of noise and disorder. We show that localization effects underpinned by quantum coherent interactions should be observable within realistic parameter regimes in chains with a larger number o

High intensity interval training exercise-induced physiological changes and their potential influence on metabolic syndrome clinical biomarkers: a meta-analysis

Abstract: Background: Despite the current debate about the effects of high intensity interval training (HIIT), HIIT elicits big morpho-physiological benefit on Metabolic Syndrome (MetS) treatment. However, no review or meta-analysis has compared the effects of HIIT to non-exercising controls in MetS variables. The aim of this study was to determine through a systematic review, the effectiveness of HIIT on MetS clinical variables in adults. Methods: Studies had to be randomised controlled trials, lasting at least 3 weeks, and compare the effects of HIIT on at least one of the MetS clinical variables [fasting blood glucose (BG), high-density lipoprotein (HDL-C) triglyceride (TG), systolic (SBP) or diastolic blood pressure (DBP) and waist circumference (WC)] compared to a control group. The methodological quality of the studies selected was evaluated using the PEDro scale. Results: Ten articles fulfilled the selection criteria, with a mean quality score on the PEDro scale of 6.7. Compared with controls, HIIT groups showed significant and relevant reductions in BG (− 0.11 mmol/L), SBP (− 4.44 mmHg), DBP (− 3.60 mmHg), and WC (− 2.26 cm). Otherwise, a slight increase was observed in HDL-C (+ 0.02 mmol/L). HIIT did not produce any significant changes in TG (− 1.29 mmol/L). Conclusions: HIIT improves certain clinical aspects in people with MetS (BG, SBP, DBP and WC) compared to people with MetS who do not perform physical exercise. Plausible physiological changes of HIIT interventions might be related with large skeletal muscle mass implication, improvements in the vasomotor control, better baroreflex control, reduction of the total peripheral resistance, increases in excess post-exercise oxygen consumption, and changes in appetite and satiety mechanisms

Tetrahedron and 3D reflection equations from quantized algebra of functions

Soibelman's theory of quantized function algebra A_q(SL_n) provides a representation theoretical scheme to construct a solution of the Zamolodchikov tetrahedron equation. We extend this idea originally due to Kapranov and Voevodsky to A_q(Sp_{2n}) and obtain the intertwiner K corresponding to the quartic Coxeter relation. Together with the previously known 3-dimensional (3D) R matrix, the K yields the first ever solution to the 3D analogue of the reflection equation proposed by Isaev and Kulish. It is shown that matrix elements of R and K are polynomials in q and that there are combinatorial and birational counterparts for R and K. The combinatorial ones arise either at q=0 or by tropicalization of the birational ones. A conjectural description for the type B and F_4 cases is also given.Comment: 26 pages. Minor correction

CSF heavy neurofilament may discriminate and predict motor neuron diseases with upper motor neuron involvement

Objective: To assess whether phosphorylated neurofilament heavy chain (pNfH) can discriminate different upper motor neuron (UMN) syndromes, namely, ALS, UMN-predominant ALS, primary lateral sclerosis (PLS) and hereditary spastic paraparesis (hSP) and to test the prognostic value of pNfH in UMN diseases. Methods: CSF and serum pNfH were measured in 143 patients presenting with signs of UMN and later diagnosed with classic/bulbar ALS, UMNp-ALS, hSP, and PLS. Between-group comparisons were drawn by ANOVA and receiver operating characteristic (ROC) analysis was performed. The prognostic value of pNfH was tested by the Cox regression model. Results: ALS and UMNp-ALS patients had higher CSF pNfH compared to PLS and hSP (p < 0.001). ROC analysis showed that CSF pNfH could differentiate ALS, UMNp-ALS included, from PLS and hSP (AUC = 0.75 and 0.95, respectively), while serum did not perform as well. In multivariable survival analysis among the totality of UMN patients and classic/bulbar ALS, CSF pNfH independently predicted survival. Among UMNp-ALS patients, only the progression rate (HR4.71, p = 0.01) and presence of multifocal fasciculations (HR 15.69, p = 0.02) were independent prognostic factors. Conclusions: CSF pNfH is significantly higher in classic and UMNp-ALS compared to UMN diseases with a better prognosis such as PLS and hSP. Its prognostic role is confirmed in classic and bulbar ALS, but not among UMNp, where clinical signs remained the only independent prognostic factors

MicroRNA 199b-5p delivery through stable nucleic acid lipid particles (SNALPs) in tumorigenic cell lines

MicroRNA (miR)-199b-5p has been shown to regulate Hes-1, a downstream effector of the canonical Notch and noncanonical SHH pathways, whereby it impairs medulloblastoma (MB) cancer stem cells (CSCs) through a decrease in the CD133+/CD15+ cell population. Here, we have developed stable nucleic acid lipid particles (SNALPs) that encapsulate miR-199b-5p. The efficacy of the miR- 199b-5p delivery by these SNALPs is demonstrated by significant impairment of Hes-1 levels and CSC markers in a range of different tumorigenic cell lines: colon (HT- 29, CaCo-2, and SW480), breast (MDA-MB231T and MCF-7), prostate (PC-3), glioblastoma (U-87), and MB(Daoy, ONS-76, and UW-228). After treatment with SNALP miR-199b-5p, there is also impairment of cell pro- liferation and no signs of apoptosis, as measured by cas- pases 3/7 activity and annexin V fluorescence cell sorter analyses. These data strengthen the importance of such carriers for miRNA delivery, which show no cytotoxic effects and provide optimal uptake into cells. Thus, efficient target downregulation in different tumorigenic cell lines will be the basis for future preclinical studies

Edukasi Internet Sehat pada Anak-Anak di SD Negeri Donoharjo

Pandemi COVID-19 telah mengubah sektor pendidikan, memaksa peralihan dari pembelajaran tatap muka menjadi jarak jauh. Teknologi menjadi penting, termasuk penggunaan Microsoft Word untuk tugas sekolah. Namun, banyak fitur penting yang belum diajarkan di sekolah, sehingga efisiensi dan efektivitas tugas siswa terbatas. Oleh karena itu, pelatihan penggunaan Microsoft Word bagi siswa sangat dibutuhkan. Tujuan pengabdian ini adalah untuk menyelenggarakan pelatihan tersebut, dengan menyajikan materi tentang fitur Microsoft Word melalui modul pembelajaran dan pengajaran langsung. Metode yang digunakan meliputi perencanaan melalui survei ke SD Marsudirini, persiapan dengan penyusunan modul dan persiapan kebutuhan, pelaksanaan pengabdian, dan evaluasi untuk perbaikan di masa depan. Hasilnya, diharapkan siswa kelas 4 SD Marsudirini Yogyakarta dapat memahami fitur Microsoft Word dalam mengerjakan tugas sekolah