Inactivation of CK1α in multiple myeloma empowers drug cytotoxicity by affecting AKT and β-catenin survival signaling pathways.

Recent evidence indicates that protein kinase CK1α may support the growth of multiple myeloma (MM) plasma cells. Here, by analyzing a large cohort of MM cases, we found that high CK1α mRNA levels are virtually associated with all MM patients. Moreover, we provided functional evidence that CK1α activity is essential for malignant plasma cell survival even in the protective niche generated by co-cultures with bone marrow stromal cells.

Major infections, secondary cancers and autoimmune diseases occur in different clinical subsets of chronic lymphocytic leukaemia patients.

Background: Major infections (MIs), secondary cancers (SCs) and autoimmune diseases (ADs) are the most common and relevant complications in patients with chronic lymphocytic leukaemia.

Methods: We performed a single-centre retrospective study to investigate the prevalence of the above quoted complications, the association with most important prognostic markers and their impact on survival (n = 795).

Results: Almost one out of three patients experienced at least one complication and only 0.

ROTational AThErectomy in acute coronary syndrome: early and midterm outcomes from a multicentre registry.

Aims: The safety and efficacy of rotational atherectomy (RA) in patients presenting with non-ST-elevation myocardial infarction (NSTE-ACS) remain to be defined. The aim of our study was to assess the safety and efficacy of RA in NSTE-ACS patients with reference to both short- and long-term follow-up.

Methods And Results: This was an observational retrospective registry which enrolled all consecutive patients undergoing RA, comparing patients with stable angina (SA) and NSTE-ACS.

Association of environmental enrichment and locomotor stimulation in a rodent model of cerebral palsy: Insights of biological mechanisms.

Several physiotherapy approaches are used with different aims in the treatment of cerebral palsy (CP), such as the early stimulation and the locomotor training, but their biological effects, isolated or combined, are not completely known. In animals models, these strategies can be compared, with due translational restrictions, to the environmental enrichment (EE), that involves the enhancement of animal's physical and social environment, and locomotor stimulation (LS), that can be performed using the treadmill adapted for rats. This study was designed to describe which biological and functional mechanisms underlying rehabilitative process in clinical practice.

Protein kinase CK2 regulates AKT, NF-κB and STAT3 activation, stem cell viability and proliferation in acute myeloid leukemia.

Protein kinase CK2 sustains acute myeloid leukemia cell growth, but its role in leukemia stem cells is largely unknown. Here, we discovered that the CK2 catalytic α and regulatory β subunits are consistently expressed in leukemia stem cells isolated from acute myeloid leukemia patients and cell lines. CK2 inactivation with the selective inhibitor CX-4945 or RNA interference induced an accumulation of leukemia stem cells in the late S-G2-M phases of the cell cycle and triggered late-onset apoptosis.

Reaction rate of a composite core-shell nanoreactor with multiple nanocatalysts.

We present a detailed theory for the total reaction rate constant of a composite core-shell nanoreactor, consisting of a central solid core surrounded by a hydrogel layer of variable thickness, where a given number of small catalytic nanoparticles are embedded at prescribed positions and are endowed with a prescribed surface reaction rate constant. Besides the precise geometry of the assembly, our theory accounts explicitly for the diffusion coefficients of the reactants in the hydrogel and in the bulk as well as for their transfer free energy jump upon entering the hydrogel shell. Moreover, we work out an approximate analytical formula for the overall rate constant, which is valid in the physically relevant range of geometrical and chemical parameters.

Hematopoietic, Mesenchymal, and Immune Cells Are More Enhanced in Bone Marrow than in Peripheral Blood from Granulocyte Colony-Stimulating Factor Primed Healthy Donors.

The use of granulocyte colony-stimulating factor (G-CSF) primed bone marrow (G-BM) has been recently considered as an alternative to mobilized hematopoietic stem cells from peripheral blood (G-PB), especially in the haploidentical transplant setting. The purpose of this study was to compare the effect of in vivo G-CSF priming on BM and PB hematopoietic, mesenchymal (MSC), and immune cells. Forty healthy donors undergoing BM harvest for haploidentical transplant were given subcutaneous recombinant human G-CSF for 7 days.

Correction: Theory of diffusion-influenced reactions in complex geometries.

Correction for 'Theory of diffusion-influenced reactions in complex geometries' by Marta Galanti et al., Phys. Chem.

Theory of diffusion-influenced reactions in complex geometries.

Chemical transformations involving the diffusion of reactants and subsequent chemical fixation steps are generally termed "diffusion-influenced reactions" (DIR). Virtually all biochemical processes in living media can be counted among them, together with those occurring in an ever-growing number of emerging nano-technologies. The role of the environment's geometry (obstacles, compartmentalization) and distributed reactivity (competitive reactants, traps) is key in modulating the rate constants of DIRs, and is therefore a prime design parameter.

Targeting CK2-driven non-oncogene addiction in B-cell tumors.

Genetic mutations of oncogenes often underlie deranged cell growth and altered differentiation pathways leading to malignant transformation of B-lymphocytes. However, addiction to oncogenes is not the only drive to lymphoid tumor pathogenesis. Dependence on non-oncogenes, which act by propelling basic mechanisms of cell proliferation and survival, has also been recognized in the pathobiology of lymphoid leukemias, lymphomas and multiple myeloma.

Amyloid-Related Imaging Abnormalities (ARIA) in Immunotherapy Trials for Alzheimer's Disease: Need for Prognostic Biomarkers?

At the 8th International Conference on Clinical Trials in Alzheimer's Disease held November 5-7, 2015 in Barcelona, Spain, promising data were presented on two candidate Alzheimer's disease immunotherapeutic agents, gantenerumab and aducanumab. Trial results demonstrated that the implementation of cerebrospinal fluid and Aβ-PET biomarkers improves trial enrichment and outcome, which has led to a change in targeting strategy as clinical trials would be conducted with earlier, even presymptomatic, stages of the disease. Promising findings of outcomes, as measured by Aβ-PET and cerebrospinal fluid tau and P-tau, were, nevertheless, associated with antibody dose-dependent increased risk of severe adverse effects, specifically amyloid-related imaging abnormalities (ARIA).

Simulation and Theory of Antibody Binding to Crowded Antigen-Covered Surfaces.

In this paper we introduce a fully flexible coarse-grained model of immunoglobulin G (IgG) antibodies parametrized directly on cryo-EM data and simulate the binding dynamics of many IgGs to antigens adsorbed on a surface at increasing densities. Moreover, we work out a theoretical model that allows to explain all the features observed in the simulations. Our combined computational and theoretical framework is in excellent agreement with surface-plasmon resonance data and allows us to establish a number of important results.

Evading the Vainshtein Mechanism with Anomalous Gravitational Wave Speed: Constraints on Modified Gravity from Binary Pulsars.

By using observations of the Hulse-Taylor pulsar, we constrain the gravitational wave (GW) speed to the level of 10(-2). We apply this result to scalar-tensor theories that generalize Galileon 4 and 5 models, which display anomalous propagation speed and coupling to matter for GWs. We argue that this effect survives conventional screening due to the persistence of a scalar field gradient inside virialized overdensities, which effectively "pierces" the Vainshtein screening.

Which cephalometric analysis for maxillo-mandibular surgery in patients with obstructive sleep apnoea syndrome?

Maxillo-mandibular advancement MMA is considered an efficacious treatment for patients affected by severe obstructive sleep apnoea syndrome (OSAS). Even though OSAS improvement is the main goal of MMA, excessive maxillo-mandibular protrusion should be avoided to guarantee pleasant postoperative facial aesthetics. In order to attain such a result, the amount of MMA should be planned preoperatively by both aesthetic and cephalometric analyses.

A headlight on liquid biopsies: a challenging tool for breast cancer management.

Breast cancer is the most frequent carcinoma and second most common cause of cancer-related mortality in postmenopausal women. The acquisition of somatic mutations represents the main mechanism through which cancer cells overcome physiological cellular signaling pathways (e.g.

Conformation-controlled binding kinetics of antibodies.

Antibodies are large, extremely flexible molecules, whose internal dynamics is certainly key to their astounding ability to bind antigens of all sizes, from small hormones to giant viruses. In this paper, we build a shape-based coarse-grained model of IgG molecules and show that it can be used to generate 3D conformations in agreement with single-molecule Cryo-Electron Tomography data. Furthermore, we elaborate a theoretical model that can be solved exactly to compute the binding rate constant of a small antigen to an IgG in a prescribed 3D conformation.

Validation of Clinicoradiological Criteria for the Diagnosis of Cerebral Amyloid Angiopathy-Related Inflammation.

Importance: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is an important diagnosis to reach in clinical practice because many patients with the disease respond to immunosuppressive therapy. Reliable noninvasive diagnostic criteria for CAA-ri would allow some patients to avoid the risk of brain biopsy.

Objective: To test the sensitivity and specificity of clinical and neuroimaging-based criteria for CAA-ri.

Cerebrospinal Fluid Anti-Amyloid-β Autoantibodies and Amyloid PET in Cerebral Amyloid Angiopathy-Related Inflammation.

We report a biomarker and genetic evaluation of four patients with cerebral amyloid angiopathy-related inflammation (CAA-ri) treated with corticosteroids. Patients presented with focal symptomatology and cognitive impairment. MRI revealed cortical microbleeds and asymmetrical hyperintense white matter lesions (WML).