Investigation of the Effects and Mechanisms of Anticancer Action of a Ru(II)-Arene Iminophosphorane Compound in Triple Negative Breast Cancer Cells

Triple negative breast cancer (TNBC) is one of the breast cancers with poorer prognosis and survival rates. TNBC has a disproportionally high incidence and mortality in women of African descent. We report on the evaluation of Ru-IM ( 1 ), a water-soluble organometallic ruthenium compound, in TNBC cell lines derived from patients of European (MDA-MB-231) and African (HCC-1806) ancestry (including IC₅₀ values, cellular and organelle uptake, cell death pathways, cell cycle, effects on migration, invasion, and angiogenesis, a preliminary proteomic analysis, and an NCI 60 cell-line panel screen). 1 was previously found highly efficacious in MDA-MB-231 cells and xenografts, with little systemic toxicity and preferential accumulation in the tumor. We observe a similar profile for this compound in the two cell lines studied, which includes high cytotoxicity, apoptotic behavior and potential antimetastatic and antiangiogenic properties. Cytokine M-CSF, involved in the PI3/AKT pathway, shows protein expression inhibition with exposure to 1 . We also demonstrate a p53 independent mechanism of action.     

Synthetic Antibody Mimics Based on Cancer-Targeting Immunostimulatory Peptides

De novo cancer-targeting immunostimulatory peptides have been designed and developed as synthetic antibody mimics. A series of bifunctional peptides incorporating NKp30-binding and NK-cell-activating domains were synthesized as linear dimers and then extended into branching trimeric peptides by the incorporation of GRP78-targeting and tumor-cell-binding sequences. A selected trimeric peptide from this small set of peptides displayed binding capabilities on GRP78⁺ HepG2 and A549 target cells. Cell binding diminished in the presence of an anti-GRP78 peptide blocker, thus suggesting GRP78-binding dependence. Similarly, the selected trimeric peptide was also found to exhibit NK cell binding in an NKp30-dependent manner, which translated into NK cell activation as indicated by cytokine secretion. In co-culture, fluorescence microscopy revealed that the target GFP-expressing A549 cells were visibly associated with the effector NK cells when pre-activated with lead trimeric peptide. Accordingly, A549 cells were found to be compromised, as evidenced by the loss of GFP signal and notable detection of early-/late-stage apoptosis. Investigation of the immunological markers related to toxicity revealed detectable secretion of pro-inflammatory cytokines and chemokines, including IFN-γ, TNF-α, and IL-8. Furthermore, administration of peptide-activated NK cells into A549-tumor-bearing mice resulted in a consistent decrease in tumor growth when compared to the untreated control group. Taken together, the identification of a lead trimeric peptide capable of targeting and activating NK cells’ immunotoxicity directly towards GRP78⁺/B7H6^- tumors provides a novel proof-of-concept for the development of cancer-targeting immunostimulatory peptide ligands that mimic antibody-targeting and -activating functions related to cancer immunotherapy applications.     

Contribution of soil compositions,harvested times and varieties on chemical fingerprint of Italian and Turkish citrus cultivars

This paper aims to define the stability over the time of chemical elemental patterns in some citrus varieties of PGI (Protected Geographical Indication) and not PGI Interdonato and Lunario cultivars coming from Italy and Turkey and to set up a range of markers useful to trace their geographical origin. During the 2015–2017 growing seasons, all fruits were collected and subjected to Inductively Coupled Mass spectrometry (ICP-MS) analysis, in order to determine the multielemental chemical profiles. The chemical variability was calculated for each element by Multi-way analysis of variance. The results highlighted how the measured Cr, Ni, Al, K, Fe and Zn levels mainly depend on the soil composition and the fingerprint allow to trace the geographical origins. Moreover, the stepwise linear discriminant analysis (SLDA) has allowed to correctly classify the 100% of lemon pulps provenances, based on Ni, Al, K, Ca and Na contents. Finally, our study demonstrates the role played by harvest years, variety and soils composition whose interaction contributed to define the chemical fingerprints.     

ARDEA—An MAV with skills for future planetary missions

We introduce a prototype flying platform for planetary exploration: autonomous robot design for extraterrestrial applications (ARDEA). Communication with unmanned missions beyond Earth orbit suffers from time delay, thus a key criterion for robotic exploration is a robot's ability to perform tasks without human intervention. For autonomous operation, all computations should be done on‐board and Global Navigation Satellite System (GNSS) should not be relied on for navigation purposes. Given these objectives ARDEA is equipped with two pairs of wide‐angle stereo cameras and an inertial measurement unit (IMU) for robust visual‐inertial navigation and time‐efficient, omni‐directional 3D mapping. The four cameras cover a $240^{°}$ vertical field of view, enabling the system to operate in confined environments such as caves formed by lava tubes. The captured images are split into several pinhole cameras, which are used for simultaneously running visual odometries. The stereo output is used for simultaneous localization and mapping, 3D map generation and collision‐free motion planning. To operate the vehicle efficiently for a variety of missions, ARDEA's capabilities have been modularized into skills which can be assembled to fulfill a mission's objectives. These skills are defined generically so that they are independent of the robot configuration, making the approach suitable for different heterogeneous robotic teams. The diverse skill set also makes the micro aerial vehicle (MAV) useful for any task where autonomous exploration is needed. For example terrestrial search and rescue missions where visual navigation in GNSS‐denied indoor environments is crucial, such as partially collapsed man‐made structures like buildings or tunnels. We have demonstrated the robustness of our system in indoor and outdoor field tests.     

Deciphering the Immunological Phenomenon of Adaptive Natural Killer (NK) Cells and Cytomegalovirus (CMV)

Natural killer (NK) cells play a significant and vital role in the first line of defense against infection through their ability to target cells without prior sensitization. They also contribute significantly to the activation and recruitment of both innate and adaptive immune cells through the production of a range of cytokines and chemokines. In the context of cytomegalovirus (CMV) infection, NK cells and CMV have co-evolved side by side to employ several mechanisms to evade one another. However, during this co-evolution the discovery of a subset of long-lived NK cells with enhanced effector potential, increased antibody-dependent responses and the potential to mediate immune memory has revolutionized the field of NK cell biology. The ability of a virus to imprint on the NK cell receptor repertoire resulting in the expansion of diverse, highly functional NK cells to this day remains a significant immunological phenomenon that only occurs in the context of CMV. Here we review our current understanding of the development of these NK cells, commonly referred to as adaptive NK cells and their current role in transplantation, infection, vaccination and cancer immunotherapy to decipher the complex role of CMV in dictating NK cell functional fate.     

Recognition of facial affect in psychopathic offenders.

The authors examined the reliability of facial affect processing deficits found in psychopathic individuals (R. Blair et al., 2004) and whether they could be modified by attentional set. One hundred eleven offenders, classified using the Psychopathy Checklist-Revised (R. Hare, 2003) and Welsh Anxiety Scale (G. Welsh, 1956), performed a facial affect recognition task under 2 conditions. On the basis of research linking psychopathy, amygdala dysfunction, and deficits in facial affect recognition, the authors predicted that psychopathic offenders would display performance deficits when required to identify the emotional expression of particular faces. In addition, given evidence linking the affective processing deficits in psychopathy to focus of attention, the authors predicted that any deficits in facial affect processing would disappear when participants could anticipate which affective cues would be relevant on a given trial. Contrary to expectation, psychopathic offenders performed as well as controls in both conditions. The authors conclude that the conditions that reveal affective deficits in psychopathic individuals require further specification. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electrical cardioversion of atrial fibrillation or flutter with conscious sedation in the age of cost containment

OBJECTIVE: To determine if there is a significant difference in the degree of pelvic organ prolapse assigned during examination in the standing position compared with the dorsal lithotomy position with the patient performing maximal Valsalva maneuver. METHODS: Fifty-one women with symptoms of pelvic organ prolapse were examined in both the dorsal lithotomy position, while performing maximal Valsalva, and in the standing position at the same visit by one of two examiners. Nine site-specific measures and summary stages were recorded, as outlined by the International Continence Society's classification system for pelvic organ prolapse. The data were analyzed by Wilcoxon signed-rank test and correlation coefficients. RESULTS: The mean age was 52 +/- 15 years. Excellent correlation was noted between all six points representing the vaginal prolapse. The R values for point Aa were 0.97, Ba 0.96, C 0.98, Ap 0.97, Bp 0.96, and D 0.97. The total vaginal length, perineal body, and genital hiatus measurements were performed in the dorsal lithotomy position with the patient at rest and were not repeated. The stages were identical in 48 of 51 patients. The average stage in the dorsal lithotomy position was 2.3 and in the standing position, 2.3. There was no statistically significant difference between the stage or any of the measured points in the dorsal lithotomy and standing examinations. CONCLUSION: The degree of pelvic organ prolapse can be assessed adequately in the dorsal lithotomy position with the patient performing maximal Valsalva. It is not necessary to routinely repeat the examination in the standing position.     

Fundamentals of Materials Selection for Light‐Emitting Electrochemical Cells

The in situ formation of a light‐emitting p–n or p–i–n junction in light‐emitting electrochemical cells (LECs) necessitates mixed ionic–electronic conductors in the active layer. This unique characteristic requires electronic, luminescent, and ionic ingredients that work synergistically in the LECs. The material requirements that lead to promising electroluminescent properties are discussed and the important components reported so far are surveyed. Particular attention is paid to the working mechanisms behind junction formation and stabilization to create efficient and stable electroluminescence in conjugated‐polymer‐based LECs. Keeping these fundamentals in mind explains how LEC devices have evolved from classic conjugated polymer blends into highly stable crosslinked, hybrid composite, and stretchable device architectures. To conclude, a future development strategy is proposed based on a dual approach: develop new materials specifically for LEC devices and explore novel ways to efficiently process and stabilize the p–i–n junction, which will drive improvements in both LEC external quantum efficiency and operating lifetime toward truly low‐cost solid‐state lighting applications.