Structure of the microtubule anchoring factor NEDD1 bound to the γ-tubulin ring complex.

The γ-tubulin ring complex (γ-TuRC) is an essential multiprotein assembly, in which γ-tubulin, GCP2-6, actin, MZT1 and MZT2 form an asymmetric cone-shaped structure that provides a template for microtubule nucleation. The γ-TuRC is recruited to microtubule organizing centers (MTOCs), such as centrosomes and pre-existing mitotic spindle microtubules, via the evolutionarily-conserved attachment factor NEDD1. NEDD1 contains an N-terminal WD40 domain that binds to microtubules, and a C-terminal domain that associates with the γ-TuRC.

Partial closure of the γ-tubulin ring complex by CDK5RAP2 activates microtubule nucleation.

Microtubule nucleation is templated by the γ-tubulin ring complex (γ-TuRC), but its structure deviates from the geometry of α-/β-tubulin in the microtubule, explaining the complex's poor nucleating activity. Several proteins may activate the γ-TuRC, but the mechanisms underlying activation are not known. Here, we determined the structure of the porcine γ-TuRC purified using CDK5RAP2's centrosomin motif 1 (CM1).

Changes in Ultrasound Parameters of the Median Nerve at Different Positions of the Radiocarpal Joint in Patients with Carpal Tunnel Syndrome.

Ultrasound imaging (US) is being increasingly used to aid in the diagnosis of entrapment neuropathies. This study aims to evaluate the shear modulus and cross-sectional area (CSA) of the median nerve in patients with carpal tunnel syndrome (CTS). A total of 35 patients with CTS participated in the study.

The Use of Physiotherapy in the Conservative Treatment of Cubital Tunnel Syndrome: A Critical Review of the Literature.

Background: The lack of a clear answer regarding the efficacy of physiotherapy in the treatment of cubital tunnel syndrome (CuTS) has led to attempts to critically assess the scientific studies conducted to date.

Materials And Methods: Two databases (MEDLINE via PubMed and PEDro) and Google Scholar were used to search for papers. The inclusion criteria were randomized controlled trials, case series, and case reports that evaluate the effects of physiotherapy in the treatment of patients with CuTS.

CAMSAPs and nucleation-promoting factors control microtubule release from γ-TuRC.

γ-Tubulin ring complex (γ-TuRC) is the major microtubule-nucleating factor. After nucleation, microtubules can be released from γ-TuRC and stabilized by other proteins, such as CAMSAPs, but the biochemical cross-talk between minus-end regulation pathways is poorly understood. Here we reconstituted this process in vitro using purified components.

Healthiness as a Virtue: The Healthism of mHealth and the Challenges to Public Health.

Mobile health (mHealth) technologies for self-monitoring health-relevant parameters such as heart frequency, sleeping patterns or exercise regimes aim at fostering healthy behavior change and increasing the individual users to promote and maintain their health. We argue that this aspect of mHealth supports healthism, the increasing shift from institutional responsibility for public health toward individual engagement in maintaining health as well as mitigating health risks. Moreover, this healthist paradigm leads to a shift from understanding health as the absence of illness to regarding health as the performance of certain rituals in order to project healthiness.

Malaria Detection Using Advanced Deep Learning Architecture.

Malaria is a life-threatening disease caused by parasites that are transmitted to humans through the bites of infected mosquitoes. The early diagnosis and treatment of malaria are crucial for reducing morbidity and mortality rates, particularly in developing countries where the disease is prevalent. In this article, we present a novel convolutional neural network (CNN) architecture for detecting malaria from blood samples with a 99.

A nucleotide binding-independent role for γ-tubulin in microtubule capping and cell division.

The γ-tubulin ring complex (γ-TuRC) has essential roles in centrosomal and non-centrosomal microtubule organization during vertebrate mitosis. While there have been important advances in understanding γ-TuRC-dependent microtubule nucleation, γ-TuRC capping of microtubule minus-ends remains poorly characterized. Here, we utilized biochemical reconstitutions and cellular assays to characterize the human γ-TuRC's capping activity.

Ethical Issues in Social Science Research Employing Big Data.

This paper analyzes the ethics of social science research (SSR) employing big data. We begin by highlighting the research gap found on the intersection between big data ethics, SSR and research ethics. We then discuss three aspects of big data SSR which make it warrant special attention from a research ethics angle: (1) the interpretative character of both SSR and big data, (2) complexities of anticipating and managing risks in publication and reuse of big data SSR, and (3) the paucity of regulatory oversight and ethical recommendations on protecting individual subjects as well as societies when conducting big data SSR.

Biochemical reconstitutions reveal principles of human γ-TuRC assembly and function.

The formation of cellular microtubule networks is regulated by the γ-tubulin ring complex (γ-TuRC). This ∼2.3 MD assembly of >31 proteins includes γ-tubulin and GCP2-6, as well as MZT1 and an actin-like protein in a "lumenal bridge" (LB).

Real-time neural network based predictor for cov19 virus spread.

Since the epidemic outbreak in early months of 2020 the spread of COVID-19 has grown rapidly in most countries and regions across the World. Because of that, SARS-CoV-2 was declared as a Public Health Emergency of International Concern (PHEIC) on January 30, 2020, by The World Health Organization (WHO). That's why many scientists are working on new methods to reduce further growth of new cases and, by intelligent patients allocation, reduce number of patients per doctor, what can lead to more successful treatments.

Neural network powered COVID-19 spread forecasting model.

Virus spread prediction is very important to actively plan actions. Viruses are unfortunately not easy to control, since speed and reach of spread depends on many factors from environmental to social ones. In this article we present research results on developing Neural Network model for COVID-19 spread prediction.

Purification of Affinity Tag-free Recombinant Tubulin from Insect Cells.

α/β-tubulin heterodimers, which can harbor diverse isotypes and post-translational modifications, polymerize into microtubules that are fundamental to many cellular processes. Due to long-standing challenges in generating recombinant tubulin, however, it has been difficult to examine the properties of specific tubulin isotypes. Here, we provide a protocol for purifying milligrams of affinity tag-free, isotypically pure recombinant tubulin.

MZT Proteins Form Multi-Faceted Structural Modules in the γ-Tubulin Ring Complex.

Microtubule organization depends on the γ-tubulin ring complex (γ-TuRC), a ∼2.3-MDa nucleation factor comprising an asymmetric assembly of γ-tubulin and GCP2-GCP6. However, it is currently unclear how the γ-TuRC-associated microproteins MZT1 and MZT2 contribute to the structure and regulation of the holocomplex.

Asymmetric Molecular Architecture of the Human γ-Tubulin Ring Complex.

The γ-tubulin ring complex (γ-TuRC) is an essential regulator of centrosomal and acentrosomal microtubule formation, yet its structure is not known. Here, we present a cryo-EM reconstruction of the native human γ-TuRC at ∼3.8 Å resolution, revealing an asymmetric, cone-shaped structure.

The synthetic diazonamide DZ-2384 has distinct effects on microtubule curvature and dynamics without neurotoxicity.

Microtubule-targeting agents (MTAs) are widely used anticancer agents, but toxicities such as neuropathy limit their clinical use. MTAs bind to and alter the stability of microtubules, causing cell death in mitosis. We describe DZ-2384, a preclinical compound that exhibits potent antitumor activity in models of multiple cancer types.

Loss of function of the Drosophila Ninein-related centrosomal protein Bsg25D causes mitotic defects and impairs embryonic development.

The centrosome-associated proteins Ninein (Nin) and Ninein-like protein (Nlp) play significant roles in microtubule stability, nucleation and anchoring at the centrosome in mammalian cells. Here, we investigate Blastoderm specific gene 25D (Bsg25D), which encodes the only Drosophila protein that is closely related to Nin and Nlp. In early embryos, we find that Bsg25D mRNA and Bsg25D protein are closely associated with centrosomes and astral microtubules.

Microtubule-associated proteins control the kinetics of microtubule nucleation.

Microtubules are born and reborn continuously, even during quiescence. These polymers are nucleated from templates, namely γ-tubulin ring complexes (γ-TuRCs) and severed microtubule ends. Using single-molecule biophysics, we show that nucleation from γ-TuRCs, axonemes and seed microtubules requires tubulin concentrations that lie well above the critical concentration.

Microtubules accelerate the kinase activity of Aurora-B by a reduction in dimensionality.

Aurora-B is the kinase subunit of the Chromosome Passenger Complex (CPC), a key regulator of mitotic progression that corrects improper kinetochore attachments and establishes the spindle midzone. Recent work has demonstrated that the CPC is a microtubule-associated protein complex and that microtubules are able to activate the CPC by contributing to Aurora-B auto-phosphorylation in trans. Aurora-B activation is thought to occur when the local concentration of Aurora-B is high, as occurs when Aurora-B is enriched at centromeres.

Variations on the single-molecule assay for microtubule-associated proteins and kinesins.

The direct observation of single kinesins and microtubule-associated proteins (MAPs) has become a core tool for cytoskeleton research. We outline several variations to the core experiment that allow the researcher to explore structural and biophysical mechanisms underlying kinesin motility and MAP function.

Improved helix and kink characterization in membrane proteins allows evaluation of kink sequence predictors.

Although the α-helical secondary structure of proteins is well-defined, the exact causes and structures of helical kinks are not. This is especially important for transmembrane (TM) helices of integral membrane proteins, many of which contain kinks providing functional diversity despite predominantly helical structure. We have developed a Monte Carlo method based algorithm, MC-HELAN, to determine helical axes alongside positions and angles of helical kinks.

Structural studies of a peptide with immune modulating and direct antimicrobial activity.

The structure and function of the synthetic innate defense regulator peptide 1018 was investigated. This 12 residue synthetic peptide derived by substantial modification of the bovine cathelicidin bactenecin has enhanced innate immune regulatory and moderate direct antibacterial activities. The solution state NMR structure of 1018 in zwitterionic dodecyl phosphocholine (DPC) micelles indicated an α-helical conformation, while secondary structures, based on circular dichroism measurements, in anionic sodium dodecyl sulfate (SDS) and phospholipid vesicles (POPC/PG in a 1:1 molar ratio) and simulations revealed that 1018 can adopt a variety of folds, tailored to its different functions.

Stereochemistry of rHint1 hydrolase assisted cleavage of P-N bond in nucleoside 5'-O-phosphoramidothioates.

The Hint-1 hydrolase assisted cleavage of the P-N bond in adenosine-5'-O-[N-(tryptophanylamide)]phosphoramidothioate proceeds with retention of configuration at the phosphorus atom which is consistent with the formation of a covalent enzyme-substrate complex.

General route to racemic and enantiomeric carbo- and heterocyclic vinyl sulfoxides via tandem Michael addition/Horner olefination of alpha-phosphorylvinyl sulfoxides.

A new one-pot synthesis of heterocyclic and carbocyclic vinyl sulfoxides has been developed which involves reaction of alpha-phosphorylvinyl sulfoxides with carbonyl compounds bearing oxygen, nitrogen, and carbon nucleophilic centers. Use of optically active alpha-phosphorylvinyl p-tolyl sulfoxides in this tandem Michael addition/Horner olefination reaction leads to the corresponding optically active cyclic sulfoxides. In this way, a variety of optically active chromene, pyrrolizine, chinoline, and cyclopentene sulfoxides have been efficiently prepared.