Light Triggers the Antiproliferative Activity of Naphthalimide-Conjugated (η6-arene)ruthenium(II) Complexes

We report the synthesis and characterization of three half-sandwich Ru(II) arene complexes [(η⁶-arene)Ru(N,N′)L][PF₆]₂ containing arene = p-cymene, N,N′ = bipyridine, and L = pyridine meta- with methylenenaphthalimide (C1), methylene(nitro)naphthalimide (C2), or methylene(piperidinyl)naphthalimide (C3). The naphthalimide acts as an antenna for photoactivation. After 3 h of irradiation with blue light, the monodentate pyridyl ligand had almost completely dissociated from complex C3, which contains an electron donor on the naphthalimide ring, whereas only 50% dissociation was observed for C1 and C2. This correlates with the lower wavelength and strong absorption of C3 in this region of the spectrum (λ_max = 418 nm) compared with C1 and C2 (λ_max = 324 and 323 nm, respectively). All the complexes were relatively non-toxic towards A549 human lung cancer cells in the dark, but only complex C3 exhibited good photocytoxicity towards these cancer cells upon irradiation with blue light (IC₅₀ = 10.55 ± 0.30 μM). Complex C3 has the potential for use in photoactivated chemotherapy (PACT).     

A Short ERAP2 That Binds IRAP Is Expressed in Macrophages Independently of Gene Variation

The M1 zinc metalloproteases ERAP1, ERAP2, and IRAP play a role in HLA-I antigen presentation by refining the peptidome either in the ER (ERAP1 and ERAP2) or in the endosomes (IRAP). They have also been entrusted with other, although less defined, functions such as the regulation of the angiotensin system and blood pressure. In humans, ERAP1 and IRAP are commonly expressed. ERAP2 instead has evolved under balancing selection that maintains two haplotypes, one of which undergoing RNA splicing leading to nonsense-mediated decay and loss of protein. Hence, likewise in rodents, wherein the ERAP2 gene is missing, about a quarter of the human population does not express ERAP2. We report here that macrophages, but not monocytes or other mononuclear blood cells, express and secrete an ERAP2 shorter form independent of the haplotype. The generation of this “short” ERAP2 is due to an autocatalytic cleavage within a distinctive structural motif and requires an acidic micro-environment. Remarkably, ERAP2 “short” binds IRAP and the two molecules are co-expressed in the endosomes as well as in the cell membrane. Of note, the same phenomenon could be observed in some cancer cells. These data prompt us to reconsider the role of ERAP2, which might have been maintained in humans due to fulfilling a relevant function in its “short” form.     

Vacuum-based preservation of surgical specimens: An environmentally-safe step towards a formalin-free hospital

Formalin as a fixative has no practical substitutes, but is toxic and potentially carcinogenic, so caution of its use in hospitals and elsewhere is mandatory. In our hospital, preservation of surgical specimens into formalin to be transferred to pathology labs was replaced by under-vacuum sealing (UVS) tissues into plastic bags and preservation at 4 °C until transfer. Data analysis showed UVS processing to be superior in terms of staff satisfaction and of gross anatomic preservation; no problems in terms of technical feasibility or histopathologic preservation were encountered. Formalin was confined to pathology labs while its use on hospital premises was vastly reduced.     

A new framework for GLIF Interdomain Resource Reservation Architecture (GIRRA)

Many existing and emerging Scientific high-end applications (E-science) require end-to-end circuits interconnecting Grid resources for large data transfers. A few advanced networks, mainly National Research and Education Networks (NRENs), such as Surfnet, National Lambda Rail and Internet 2, now provide mechanisms for end-users to reserve and provision lightpaths via middleware referred to as Network Resource Mangers (NRMs). Although, some progress has been made in automated intra-domain lightpath services, inter-domain lightpath provisioning still requires manual intervention and presents several key challenges such as scalability of topology information exchanged, consistency and scalability of information model, security of access to the resources, hybrid networking and multi-layer lightpaths, and accounting and billing. In this paper, we describe a new architectural framework called Global Lambda Integrated Facility (GLIF) Interdomain Resource Reservation Architecture (GIRRA) with the goal to provide an integrated response to these challenges. We propose a new approach to model GLIF network domains and GOLEs as virtual switches and to describe their behavior, functionality, policy capabilities, and topology aggregation. We define an inter-domain path computation model to determine paths that meet constraints and access policy restrictions. We propose a security framework for authentication and authorization of users and a model for accounting and billing that aims to provide easy and secure access to the resources. Key aspects of the GIRRA solution are that it focuses on the inter-dependence between different challenges of inter-domain path provision, and it is built around already existing solutions for intra-domain resource provisioning.     

Intrusion Detection System for Wireless Sensor Networks Using Danger Theory Immune-Inspired Techniques

An IDS framework inspired in the Human Immune System to be applied in the wireless sensor network context is proposed. It uses an improved decentralized and customized version of the Dendritic Cell Algorithm, which allows nodes to monitor their neighborhood and collaborate to identify an intruder. The work was implemented and tested both in simulation and in real sensor platform scenarios, comparing them to each other and was also compared to a Negative Selection Theory implementation in order to demonstrate its efficiency in detecting a denial-of-sleep attack and in energy consumption. Results demonstrated the success of the proposal.     

Pep19 Has a Positive Effect on Insulin Sensitivity and Ameliorates Both Hepatic and Adipose Tissue Phenotype of Diet-Induced Obese Mice

Peptide DIIADDEPLT (Pep19) has been previously suggested to improve metabolic parameters, without adverse central nervous system effects, in a murine model of diet-induced obesity. Here, we aimed to further evaluate whether Pep19 oral administration has anti-obesogenic effects, in a well-established high-fat diet-induced obesity model. Male Swiss mice, fed either a standard diet (SD) or high-fat diet (HFD), were orally administrated for 30 consecutive days, once a day, with saline vehicle or Pep19 (1 mg/kg). Next, several metabolic, morphological, and behavioral parameters were evaluated. Oral administration of Pep19 attenuated HFD body-weight gain, reduced in approximately 40% the absolute mass of the endocrine pancreas, and improved the relationship between circulating insulin and peripheral insulin sensitivity. Pep19 treatment of HFD-fed mice attenuated liver inflammation, hepatic fat distribution and accumulation, and lowered plasma alanine aminotransferase activity. The inguinal fat depot from the SD group treated with Pep19 showed multilocular brown-fat-like cells and increased mRNA expression of uncoupling protein 1 (UCP1), suggesting browning on inguinal white adipose cells. Morphological analysis of brown adipose tissue (BAT) from HFD mice showed the presence of larger white-like unilocular cells, compared to BAT from SD, Pep19-treated SD or HFD mice. Pep19 treatment produced no alterations in mice behavior. Oral administration of Pep19 ameliorates some metabolic traits altered by diet-induced obesity in a Swiss mice model.     

Variants of HCMV UL18 Sequenced Directly from Clinical Specimens Associate with Antibody and T-Cell Responses to HCMV

Around 80% of adults worldwide carry human cytomegaloviris (HCMV). The HCMV gene UL18 is a homolog of HLA class I genes and encodes a protein with high affinity for the NK and T-cell cytotoxicity inhibitor LIR-1. UL18 was deep sequenced from blood, saliva or urine from Indonesian people with HIV (PWH) (n = 28), Australian renal transplant recipients (RTR) (n = 21), healthy adults (n = 7) and neonates (n = 4). 95% of samples contained more than one variant of HCMV UL18, as defined by carriage of nonsynonymous variations. When aligned with immunological markers of the host’s burden of HCMV, the S318N variation associated with high levels of antibody reactive with HCMV lysate in PWH over 12 months on antiretroviral therapy. The A107T variation associated with HCMV antibody levels and inflammatory biomarkers in PWH at early timepoints. Variants D32G, D248N, V250A and E252D aligned with elevated HCMV antibody levels in RTR, while M191K, E196Q and F165L were associated with HCMV-reactive T-cells and proportions of Vδ2⁻ γδ T-cells—populations linked with high burdens of HCMV. We conclude that UL18 is a highly variable gene, where variation may alter the persistent burden of HCMV and/or the host response to that burden.     

Crystallization behavior of milk fat,palm oil,palm kernel oil,and cocoa butter with and without the addition of cannabidiol

The objective of this study was to evaluate the effect of cannabidiol (CBD) on the crystallization behavior and physical properties of various fats. Anhydrous milk fat (AMF), palm oil (PO), palm kernel oil (PKO), and cocoa butter (CB) were chosen for this study, for their unique crystallization behaviors. CBD was added at 1 and 2.5% wt/wt to these fats, and the crystallization behavior was evaluated at 26°C for AMF and PO and at 22°C for PKO and CB. Control samples with no CBD were prepared and evaluated as well. Results show that CBD delayed the crystallization of all fats with the least effect observed for the PO. Slight increases in crystal size were observed with the addition of CBD for all samples. CBD did not affect the melting profile of AMF or CB, but it increased the peak temperature of PO and decreased the enthalpy of PKO. Similarly, hardness was only affected by CBD in PO samples, with harder materials obtained for samples containing 2.5% CBD. The same trend was observed for elasticity. In addition, the elasticity of AMF increased with the addition of CBD but not its hardness. Overall, this study indicates that the effect of CBD on fat crystallization is highly dependent on the type of fat used. Producers of fat-based products that are willing to include CBD in their formulations must carefully control processing conditions to ensure product quality.