Mechanisms underlying the cooperation between loss of epithelial polarity and Notch signaling during neoplastic growth in Drosophila

Aggressive neoplastic growth can be initiated by a limited number of genetic alterations, such as the well-established cooperation between loss of cell architecture and hyperactive signaling pathways. However, our understanding of how these different alterations interact and influence each other remains very incomplete. Using Drosophila paradigms of imaginal wing disc epithelial growth, we have monitored the changes in Notch pathway activity according to the polarity status of cells (scrib mutant). We show that the scrib mutation impacts the direct transcriptional output of the Notch pathway, without altering the global distribution of Su(H), the Notch dedicated transcription factor. The Notch-dependent neoplasms require however, the action of a group of transcription factors, similar to those previously identified for Ras/scrib neoplasm (namely AP-1, Stat92E, Ftz-F1, and bZIP factors), further suggesting the importance of this transcription factor network during neoplastic growth. Finally our work highlights some Notch/scrib specificities, in particular the role of the PAR domain containing bZIP transcription factor and Notch direct target Pdp1 for neoplastic growth.

Revisiting Excitotoxicity in Traumatic Brain Injury: From Bench to Bedside

Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality. Consequences vary from mild cognitive impairment to death and, no matter the severity of subsequent sequelae, it represents a high burden for affected patients and for the health care system. Brain trauma can cause neuronal death through mechanical forces that disrupt cell architecture, and other secondary consequences through mechanisms such as inflammation, oxidative stress, programmed cell death, and, most importantly, excitotoxicity. This review aims to provide a comprehensive understanding of the many classical and novel pathways implicated in tissue damage following TBI. We summarize the preclinical evidence of potential therapeutic interventions and describe the available clinical evaluation of novel drug targets such as vitamin B12 and ifenprodil, among others.

Phase-resonance Exploitation in Full-Metal 3D Periodic Structures for Single- and Multi- Wideband Applications

This paper presents a versatile full-metal 3D periodic structure based on square waveguides with non-closed resonators perforated on their walls. The complex unit-cell architecture is modelled via accurate equivalent circuits, previously characterized. The circuit model predicts the excitation of phase resonance, which will be used to optimize and design different functionalities, such as polarisation converters or absorption.

Phase-resonance Exploitation in Full-Metal 3D Periodic Structures for Single- and Multi- Wideband Applications

This paper presents a versatile full-metal 3D periodic structure based on square waveguides with non-closed resonators perforated on their walls. The complex unit-cell architecture is modelled via accurate equivalent circuits, previously characterized. The circuit model predicts the excitation of phase resonance, which will be used to optimize and design different functionalities, such as polarisation converters or absorption.

A Dual-Frequency Miniaturized Frequency Selective Surface Structure Suitable for Antenna Stealth

A tiny dual-band frequency selective surface structure is proposed in this paper. With dual-band rejection characteristics at the corresponding frequency points of the S-band and C-band, suitable for antenna stealth. To achieve miniaturization, the unit-cell architecture resembles the shape of a “S.” First of all, the author describes the parameters of the surface element, and then, the transmission characteristics of the surface element are analyzed by the equivalent circuit method. By maintaining a constant response to TE and TM polarization patterns and oblique incident angles, the suggested device ensures angular independence. The measured findings from the constructed FSS are used to validate the computed results. Finally, a new unit structure is provided for the application of FSS in antenna stealth.

Single-Cell Sequencing Demonstrates Complex Resistance Landscape in CLL and MCL Treated with BTK and BCL2 Inhibitors

The genomic landscape of resistance to targeted agents (TAs) used as monotherapy in chronic lymphocytic leukemia (CLL) is complex and often heterogeneous at the patient level. To gain insight into the clonal architecture of acquired genomic resistance to BTK inhibitors and BCL2 inhibitors in CLL, particularly in patients carrying multiple resistance mutations, we performed targeted single-cell DNA sequencing of eight patients who developed progressive disease (PD) on TAs (either class). In all cases, analysis of single-cell architecture revealed mutual exclusivity between multiple resistance mutations to the same TA class, variable clonal co-occurrence of multiple mutations affecting different TAs in patients exposed to both classes, and a phenomenon of multiple independent emergences of identical nucleotide changes leading to canonical resistance mutations. We also report the first observation of established BCL2 resistance mutations in a patient with mantle cell lymphoma (MCL) following PD on sequential monotherapy, implicating BCL2 as a venetoclax resistance mechanism in MCL. Taken together, these data reveal the significant clonal complexity of CLL and MCL progression on TAs at the nucleotide level and confirm the presence of multiple, clonally independent, mechanisms of TA resistance within each individual disease context.