The case report presents an identification process based on DNA isolated from personal belongings, including a filter mask. In May 2021, an unidentified 65-year-old male corpse was revealed by the city\'s outskirts road. Since it was impossible to use material from living relatives for comparative analysis, the samples of personal belongings of the alleged victim were used instead: clippings of the filtering face piece type 2 (FFP2) face mask (parts adhering to the nose and the earlobes, the central part of the mask), swabs from the razor (blade and shaft), toothbrush shaft, and toothbrush filaments clippings. The presented case indicates the need for collecting a wide range of samples for genetic analyses, including filter masks as an alternative item of personal belonging.
Zaprezentowany opis przypadku przedstawia próbę identyfikacji osobniczej z wykorzystaniem DNA wyizolowanego z rzeczy użytku osobistego, w tym maseczki na twarz. W maju 2021 r. przy drodze podmiejskiej znaleziono niezidentyfikowane zwłoki 65-letniego mężczyzny. Ponieważ niemożliwe było wykorzystanie do analizy porównawczej materiału od żyjących krewnych, wykorzystano rzeczy osobiste domniemanej ofiary: wycinki maski filtrującej typu 2 (FFP2) (części przylegające do nosa i małżowiny usznych, środkową część maski), wymazy z maszynki do golenia (ostrze i trzonek), wymaz z trzonka szczoteczki do zębów i wycinki z włosia szczoteczki. Przedstawiony przypadek wskazuje na potrzebę pobrania szerokiego zakresu próbek do analiz genetycznych, w tym masek filtrujących jako alternatywnego przedmiotu użytku osobistego.

Endometriosis of the cervix is a rare form of genital endometriosis, which is characterized by the appearance of tissue on the vaginal part of the cervix, similar to the tissue of the mucous membrane of the uterine cavity. We describe a clinical case in which we compared the content of cytoskeletal proteins, H3 histone modifications and DNA methylation (total and 5-hydroxymethylcytosine content) in the eutopic endometrium and in tissue from endometriosis foci on the cervix. The patient had elevated levels of estradiol, interleukin-1β and interleukin-8. At the cellular level, the content of tubulin and the marker of stable microtubules were reduced in the ectopic endometrium (by 45% and 37%, p < 0.05, respectively), but the alpha-actinin-1 content was increased (by 75%, p < 0.05) with an increase in the expression of its gene. At the same time, the total level of DNA methylation in the endometriotic focus was reduced by more than 2 times with the accumulation of the intermediate product 5-hydroxymethylcytosine (the content increased by more than 3 times), probably due to an increase in the content of tet methylcytosine dioxygenase 1 (more than 4 times).

The Brugada syndrome (BrS) is an inherited cardiac disorder predisposing to ventricular arrhythmias. Despite considerable efforts, its genetic basis and cellular mechanisms remain largely unknown. The objective of this study was to identify a new susceptibility gene for BrS through familial investigation.
Whole-exome sequencing performed in a three-generation pedigree with five affected members allowed the identification of one rare non-synonymous substitution (p.R211H) in RRAD, the gene encoding the RAD GTPase, carried by all affected members of the family. Three additional rare missense variants were found in 3/186 unrelated index cases. We detected higher levels of RRAD transcripts in subepicardium than in subendocardium in human heart, and in the right ventricle outflow tract compared to the other cardiac compartments in mice. The p.R211H variant was then subjected to electrophysiological and structural investigations in human cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs). Cardiomyocytes derived from induced pluripotent stem cells from two affected family members exhibited reduced action potential upstroke velocity, prolonged action potentials and increased incidence of early afterdepolarizations, with decreased Na+ peak current amplitude and increased Na+ persistent current amplitude, as well as abnormal distribution of actin and less focal adhesions, compared with intra-familial control iPSC-CMs Insertion of p.R211H-RRAD variant in control iPSCs by genome editing confirmed these results. In addition, iPSC-CMs from affected patients exhibited a decreased L-type Ca2+ current amplitude.
This study identified a potential new BrS-susceptibility gene, RRAD. Cardiomyocytes derived from induced pluripotent stem cells expressing RRAD variant recapitulated single-cell electrophysiological features of BrS, including altered Na+ current, as well as cytoskeleton disturbances.

Astrocytes play an important role in the physiological functions of the central nervous system. In this study, contact potential differences (CPD) and capacitance gradients of the cell bodies and glial filaments of astrocytes were measured. Charge propagation properties in the astrocyte gap junctions were also studied using multimode Atomic Force Microscopy (AFM) at nanometre resolution. The CPD of the cell bodies and glial filaments were 324.2 ± 138.4 and 119.1 ± 31.7 mV, respectively. The measured capacitance gradients were 1.51 ± 0.31 and 1.98 ± 0.32 zF nm-1 , respectively. The gap junctions in the astrocytes showed no charge propagation and were not electrically sensitive. This furthers our understanding of astrocytes and other types of neuroglia. LAY DESCRIPTION: Neuroglia cells play important structural and functional roles in central nervous system (CNS). Neuroglia cells exceed the number of neurons by 10∼50 and can be divided into macroglia and microglia. Astrocytes are macroglia and are the largest and most abundant cells in the CNS. Astrocytes lack axons and dendrites and do not propagate action potentials. They have few cytoplasmic organelles, but possess abundant glial filaments, the main components of the cytoskeleton. Glial filaments are composed of the glial fibrillary acidic protein (GFAP). Astrocytes produce intercellular calcium waves in their gap junctions mediated through receptor activator (such as glutamate) to permit signal transduction._ENREF_5 In addition to their role in the support and nutrition of neurons, astrocytes are involved in various types of CNS activity including: (1) cytokine secretion for neuronal survival, growth and differentiation; (2) protection from brain injury; (3) modulation of the blood brain barrier; and (4) neuronal immunity. Bidirectional crosstalk between the astrocytes and neurons exists. Astrocytes can be activated by neurotransmitters released and can themselves release gliotransmitters to act upon neurons. Astrocytes are closely related to various disease states, including epilepsy and Alzheimer\'s disease. In this study, the electrical properties of astrocytes, including the contact potential difference (CPD) and capacitance gradients of the cell bodies and glial filaments, and charge propagation in the gap junctions were investigated at the nanometer level using quantitative Kelvin Probe Force Microscopy (KPFM) and Electrostatic Force Microscopy (EFM). The CPD of the cell bodies and glial filaments of the astrocytes were 324.2 mV and 119.1 mV, respectively. Capacitance gradients of the cell bodies and glial filaments of the astrocytes were 1.51 zF/nm and 1.98 zF/nm, respectively. Gap junctions in the astrocytes do not perform charge propagation functions and the astrocytes are not electrically sensitive. One should note that these results from KPFM and EFM were measured on dried cell and the situation might be different when studying in operando environment, still these findings aid our understanding of the electrical properties and functions of astrocytes, and further our knowledge of the electrical properties of the CNS.

Cytoskeletal networks to transmission towers are comprised of slender elements. Slender filaments bend and buckle more easily than stretch. Therefore a deforming network is expected to exhaust all possible bending-based modes before engaging filament stretch. While the large-strain bending critically determines fibrous-media response, simulations use small-strain and jointed approximations. At low resolution, these approximations inflate bending resistance and delay buckling onset. The proposed string-of-continuous-beams (SOCB) approach captures 3D nonlinear Euler bending of filaments with high fidelity at low cost. Bending geometry (i.e. angles and its differentials) is solved as primary variables, to fit a 5th order polynomial of the contour angle. Displacement, solved simultaneously as length conservation, is predicted with C3 and C6 smoothness between and within segments, using only 2 nodes. In the chosen analysis frame, in-plane and out-plane moments can be decoupled for arbitrarily-curved segments. Complex crosslink force-transfers can be specified. Simulations show that when a daughter branch is appended, the buckling resistance of a filament changes from linear to nonlinear before reversible collapse. An actin outcrop with 8 generations of mother-daughter branching produced the linear, nonlinear, and collapse regimes observed in compression experiments. \'Collapse\' was a redistribution of outcrop forces following the buckling of few strands.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by cytoplasmic protein aggregates within motor neurons. These aggregates are linked to ALS pathogenesis. Recent evidence has suggested that stress granules may aid the formation of ALS protein aggregates. Here, we summarize current understanding of stress granules, focusing on assembly and clearance. We also assess the evidence linking alterations in stress granule formation and dynamics to ALS protein aggregates and disease pathology.

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As stroke therapies are still limited to a minority of patients, efforts have been intensified to an improved understanding of pathophysiological processes during ischemia formation, potentially allowing the development of specific therapeutic interventions. In this context, cytoskeletal elements became evident as key players during the transition process towards long-lasting tissue damage. This study focused on ischemia-related alterations of the cytoskeleton with a special focus on microtubule-associated proteins and neurofilament light chains (NF-L). Immunohistochemical analyses were applied to brain sections of mice and rats after experimental stroke and to autoptic samples from a stroke patient. To consider translational aspects, a thromboembolic model of stroke in rats, closely mimicking the human situation, was used in addition to the filament-based model of focal cerebral ischemia in mice. One day after ischemia onset, immunoreactivity of microtubule-associated protein tau and microtubule-associated protein-2 (MAP2) was reduced in ischemic areas. These findings were consistently present in the ischemia-affected striatum and the neocortex. In a quite opposite fashion, ischemic areas displayed NF-L-immunoreactivity in neuropathologically altered fibers, local agglomerations probably related to degraded cell bodies and neocortical pyramidal cells. Notably, up-regulation of NF-L was also confirmed in infarcted tissue from a human brain sample. Furthermore, analyses of rodent brain tissue revealed corkscrew curl-like fibers as a special feature of MAP2 in the ischemia-affected hippocampus. In conclusion, this study provides evidence for an opposite reaction of microtubule-associated proteins and neurofilaments after focal cerebral ischemia. Accordingly, cytoskeletal elements appear as a promising target for stroke treatment.

The biological activity of a recombinant protein is routinely measured using a bioassay such as an enzyme assay. However, many proteins have no enzymatic activity and in many cases it is difficult to devise a simple and reliable approach to test their activity. Semaphorins, Ephrins, Slits, Netrins or amylin-assisted proteins have numerous activities affecting many systems and cell types in the human body. Most of them are also able to induce rapid cytoskeleton changes at least in some cell types. We assumed therefore, that such proteins might be tested based on their ability to modulate the cytoskeleton. Here we tested a number of semaphorins in an impedance based label-free platform that allows for dynamic monitoring of subtle morphological and adhesive changes. This system has proved to be a very fast, sensitive and effective way to monitor and determine the activity of such proteins. Furthermore we showed that it is possible to customize a cell-protein system by transfecting the cells with specific receptors and test the cell response following the addition of the recombinant ligand protein. Since other protein families such as Ephrins and Netrins can also influence the cytoskeleton of some cells, this approach may be applicable to a large number of proteins.

Fifteen years ago we discovered activity-dependent neuroprotective protein (ADNP), and showed that it is essential for brain formation/function. Our protein interaction studies identified ADNP as a member of the chromatin remodeling complex, SWI/SNF also associated with alternative splicing of tau and prediction of tauopathy. Recently, we have identified cytoplasmic ADNP interactions with the autophagy regulating microtubule-associated protein 1 light chain 3 (LC3) and with microtubule end-binding (EB) proteins. The ADNP-EB-binding SIP domain is shared with the ADNP snippet drug candidate, NAPVSIPQ termed NAP (davunetide). Thus, we identified a precise target for ADNP/NAP (davunetide) neuroprotection toward improved drug development.