Summary of Ford v. State of Nevada, 122 Nev. Adv. Op. 36

Appeal from jury verdict in criminal trial on grounds that prosecutors impermissibly excluded jurors based on race in violation of Batson v. Kentucky

Novel Insights into RAD52’s Structure, Function, and Druggability for Synthetic Lethality and Innovative Anticancer Therapies

Simple Summary Human RAD52 is a non-essential DNA/RNA-binding protein thought to be involved in many DNA repair mechanisms. Initially regarded as having a major role only in error-prone backup DNA repair mechanisms, RAD52 has recently gained attention because its inhibition induces synthetic lethality in cancer cells with an inactivated homologous recombination pathway (for error-free double-strand-break repair). RAD52 is thus a potential target to overcome resistance and unwanted side effects. Unfortunately, researchers still lack detailed structural and mechanistic information on RAD52 and have identified only a limited number of inhibitors, none of which are in the preclinical phase. This review summarizes the current knowledge on RAD52, highlighting the potential of its inhibition. This review also discusses the critical gaps in knowledge and sets out future directions for effective campaigns to discover RAD52 inhibitors. In recent years, the RAD52 protein has been highlighted as a mediator of many DNA repair mechanisms. While RAD52 was initially considered to be a non-essential auxiliary factor, its inhibition has more recently been demonstrated to be synthetically lethal in cancer cells bearing mutations and inactivation of specific intracellular pathways, such as homologous recombination. RAD52 is now recognized as a novel and critical pharmacological target. In this review, we comprehensively describe the available structural and functional information on RAD52. The review highlights the pathways in which RAD52 is involved and the approaches to RAD52 inhibition. We discuss the multifaceted role of this protein, which has a complex, dynamic, and functional 3D superstructural arrangement. This complexity reinforces the need to further investigate and characterize RAD52 to solve a challenging mechanistic puzzle and pave the way for a robust drug discovery campaign

Occurrence of different Canine distemper virus lineages in Italian dogs

This study describes the sequence analysis of the H gene of 7 Canine distemper virus (CDV) strains identified in dogs in Italy between years 2002-2012. The phylogenetic analysis showed that the CDV strains belonged to 2 clusters: 6 viruses were identified as Arctic-like lineage and 1 as Europe 1 lineage. These data show a considerable prevalence of Arctic-like-CDVs in the analysed dogs. The dogs and the 3 viruses more recently identified showed 4 distinctive amino acid mutations compared to all other Arctic CDV

Making GDPR Usable: A Model to Support Usability Evaluations of Privacy

We introduce a new model for evaluating privacy that builds on the criteria proposed by the EuroPriSe certification scheme by adding usability criteria. Our model is visually represented through a cube, called Usable Privacy Cube (or UP Cube), where each of its three axes of variability captures, respectively: rights of the data subjects, privacy principles, and usable privacy criteria. We slightly reorganize the criteria of EuroPriSe to fit with the UP Cube model, i.e., we show how EuroPriSe can be viewed as a combination of only rights and principles, forming the two axes at the basis of our UP Cube. In this way we also want to bring out two perspectives on privacy: that of the data subjects and, respectively, that of the controllers/processors. We define usable privacy criteria based on usability goals that we have extracted from the whole text of the General Data Protection Regulation. The criteria are designed to produce measurements of the level of usability with which the goals are reached. Precisely, we measure effectiveness, efficiency, and satisfaction, considering both the objective and the perceived usability outcomes, producing measures of accuracy and completeness, of resource utilization (e.g., time, effort, financial), and measures resulting from satisfaction scales. In the long run, the UP Cube is meant to be the model behind a new certification methodology capable of evaluating the usability of privacy, to the benefit of common users. For industries, considering also the usability of privacy would allow for greater business differentiation, beyond GDPR compliance.Comment: 41 pages, 2 figures, 1 table, and appendixe

Critical role for prokineticin 2 in CNS autoimmunity

Objective: To investigate the potential role of prokineticin 2 (PK2), a bioactive peptide involved in multiple biological functions including immune modulation, in CNS autoimmune demyelinating disease. Methods: We investigated the expression of PK2 in mice with experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), and in patients with relapsing-remitting MS. We evaluated the biological effects of PK2 on expression of EAE and on development of T-cell response against myelin by blocking PK2 in vivo with PK2 receptor antagonists. We treated with PK2 immune cells activated against myelin antigen to explore the immune-modulating effects of this peptide in vitro. Results: Pk2 messenger RNA was upregulated in spinal cord and lymph node cells (LNCs) of mice with EAE. PK2 protein was expressed in EAE inflammatory infiltrates and was increased in sera during EAE. In patients with relapsing-remitting MS, transcripts for PK2 were significantly increased in peripheral blood mononuclear cells compared with healthy controls, and PK2 serum concentrations were significantly higher. A PK2 receptor antagonist prevented or attenuated established EAE in chronic and relapsing-remitting models, reduced CNS inflammation and demyelination, and decreased the production of interferon (IFN)-γ and interleukin (IL)-17A cytokines in LNCs while increasing IL-10. PK2 in vitro increased IFN-γ and IL-17A and reduced IL-10 in splenocytes activated against myelin antigen. Conclusion: These data suggest that PK2 is a critical immune regulator in CNS autoimmune demyelination and may represent a new target for therapy

Tuning the domain wall orientation in thin magnetic strips by induced anisotropy

We report on a method to tune the orientation of in-plane magnetic domains and domain walls in thin ferromagnetic strips by manipulating the magnetic anisotropy. Uniaxial in-plane anisotropy is induced in a controlled way by oblique evaporation of magnetic thin strips. A direct correlation between the magnetization direction and the domain wall orientation is found experimentally and confirmed by micromagnetic simulations. The domain walls in the strips are always oriented along the oblique evaporation-induced easy axis, in spite of the shape anisotropy. The controlled manipulation of domain wall orientations could open new possibilities for novel devices based on domain-wall propagation

The antagonism of the prokineticin system counteracts bortezomib induced side effects: Focus on mood alterations

The development of neuropathy and of mood alterations is frequent after chemotherapy. These complications, independent from the antitumoral mechanism, are interconnected due to an overlapping in their processing pathways and a common neuroinflammatory condition. This study aims to verify whether in mice the treatment with the proteasome inhibitor bortezomib (BTZ), at a protocol capable of inducing painful neuropathy, is associated with anxiety, depression and supraspinal neuroinflammation. We also verify if the therapeutic treatment with the antagonist of the prokineticin (PK) system PC1, which is known to contrast pain and neuroinflammation, can prevent mood alterations. Mice were treated with BTZ (0.4 mg/kg three times/week for 4 weeks); mechanical allodynia and locomotor activity were evaluated over time while anxiety (dark light and marble burying test), depression (sucrose preference and swimming test) and supraspinal neuroinflammation were checked at the end of the protocol. BTZ treated neuropathic mice develop anxiety and depression. The presence of mood alterations is related to the presence of neuroinflammation and PK system activation in prefrontal cortex, hippocampus and hypothalamus with high levels of PK2 and PKR2 receptor, IL‐6 and TNF‐α, TLR4 and an upregulation of glial markers. PC1 treatment, counteracting pain, prevented the development of supraspinal inflammation and depression‐like behavior in BTZ mice

Culture-dependent and sequencing methods revealed the absence of a bacterial community residing in the urine of healthy cats

A growing number of studies suggest that the lower urinary tract of humans and dogs can harbor a urinary microbiota. Nevertheless, a certain concern has developed that the microbiota reported could be due to unaccounted contamination, especially in low-biomass samples. The aim of this study was to investigate the bacterial community which populates the urine of healthy cats using two approaches: a culture-dependent approach which consisted of the expanded quantitative urine culture (EQUC) techniques capable of identifying live bacteria not growing in standard urine cultures, and a culture-independent approach which consisted of 16S ribosomal RNA next generation sequencing (16S rRNA NGS) capable of identifying bacterial DNA and exploring microbial diversity with high resolution. To avoid confounding factors of possible bacterial contamination, the urine was sampled using ultrasound-guided cystocentesis, and several sample controls and negative controls were analyzed. The urine sampled from the 10 cats included in the study showed no bacterial growth in the EQUC procedure. Although several reads were successfully originated using 16S rRNA NGS, a comparable pattern was observed between urine samples and the negative control, and no taxa were statistically accepted as non-contaminant. Taken together, the results obtained allowed stating that no viable bacteria were present in the urine of healthy cats without lower urinary tract disease and urinary tract infections, and that the bacterial DNA detected was of contaminant origin

Prokineticin 2 upregulation in the peripheral nervous system has a major role in triggering and maintaining neuropathic pain in the chronic constriction injury model

The new chemokine Prokineticin 2 (PROK2) and its receptors (PKR1 and PKR2) have a role in inflammatory pain and immunomodulation. Here we identified PROK2 as a critical mediator of neuropathic pain in the chronic constriction injury (CCI) of the sciatic nerve in mice and demonstrated that blocking the prokineticin receptors with two PKR1-preferring antagonists (PC1 and PC7) reduces pain and nerve damage. PROK2 mRNA expression was upregulated in the injured nerve since day 3 post injury (dpi) and in the ipsilateral DRG since 6 dpi. PROK2 protein overexpression was evident in Schwann Cells, infiltrating macrophages and axons in the peripheral nerve and in the neuronal bodies and some satellite cells in the DRG. Therapeutic treatment of neuropathic mice with the PKR-antagonist, PC1, impaired the PROK2 upregulation and signalling. This fact, besides alleviating pain, brought down the burden of proinflammatory cytokines in the damaged nerve and prompted an anti-inflammatory repair program. Such a treatment also reduced intraneural oedema and axon degeneration as demonstrated by the physiological skin innervation and thickness conserved in CCI-PC1 mice. These findings suggest that PROK2 plays a crucial role in neuropathic pain and might represent a novel target of treatment for this disease