The γ-subunit of the principal G-protein from squid (Loligo forbesi) photoreceptors contains a novel N-terminal sequence

AbstractThe squid (Loligo forbesi) visual system presents as accessible a system for study of G-protein mediated signal transduction as the vertebrate rod outer segment with the added advantage that the major G-protein is a member of the Gq-class. Here the cDNA clone encoding the γ-subunit of this G-protein is reported, thereby completing the molecular cloning of the heterotrimeric G-protein. The deduced protein structure of G-γ has relatively little sequence identity with known mammalian counterparts particularly in comparison with the relatively high degree found for both the α- and β-subunits of this protein. In particular, the N-terminus of the squid visual G-γ contains a repetitive, highly charged region, rich in lysine and glutamate, that has no parallel in other G-proteins. The amino acid sequence of a number of peptides derived by chemical cleavage of G-γ accounted for much of the protein sequence predicted from the cDNA, including the unusual N-terminal region

Tuning gaps and phases of a two-subband system in a quantizing magnetic field

In this work we study the properties of a two-subband quasi-two-dimensional electron system in a strong magnetic field when the electron filling factor is equal to four. When the cyclotron energy is close to the intersubband splitting the system can be mapped onto a four-level electron system with an effective filling factor of two. The ground state is either a ferromagnetic state or a spin-singlet state, depending on the values of the inter-level splitting and Zeeman energy. The boundaries between these phases are strongly influenced by the inter-electron interaction. A significant exchange-mediated enhancement of the excitation gap results in the suppression of the electron-phonon interaction. The rate of absorption of non-equilibrium phonons is calculated as a function of Zeeman energy and inter-subband splitting. The phonon absorption rate has two peaks as a function of intersubband splitting and has a step-like structure as a function of Zeeman energy

Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial.

Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor. To investigate whether TTFields improves progression-free and overall survival of patients with glioblastoma, a fatal disease that commonly recurs at the initial tumor site or in the central nervous system. In this randomized, open-label trial, 695 patients with glioblastoma whose tumor was resected or biopsied and had completed concomitant radiochemotherapy (median time from diagnosis to randomization, 3.8 months) were enrolled at 83 centers (July 2009-2014) and followed up through December 2016. A preliminary report from this trial was published in 2015; this report describes the final analysis. Patients were randomized 2:1 to TTFields plus maintenance temozolomide chemotherapy (n = 466) or temozolomide alone (n = 229). The TTFields, consisting of low-intensity, 200 kHz frequency, alternating electric fields, was delivered (≥ 18 hours/d) via 4 transducer arrays on the shaved scalp and connected to a portable device. Temozolomide was administered to both groups (150-200 mg/m2) for 5 days per 28-day cycle (6-12 cycles). Progression-free survival (tested at α = .046). The secondary end point was overall survival (tested hierarchically at α = .048). Analyses were performed for the intent-to-treat population. Adverse events were compared by group. Of the 695 randomized patients (median age, 56 years; IQR, 48-63; 473 men [68%]), 637 (92%) completed the trial. Median progression-free survival from randomization was 6.7 months in the TTFields-temozolomide group and 4.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.52-0.76; P < .001). Median overall survival was 20.9 months in the TTFields-temozolomide group vs 16.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.53-0.76; P < .001). Systemic adverse event frequency was 48% in the TTFields-temozolomide group and 44% in the temozolomide-alone group. Mild to moderate skin toxicity underneath the transducer arrays occurred in 52% of patients who received TTFields-temozolomide vs no patients who received temozolomide alone. In the final analysis of this randomized clinical trial of patients with glioblastoma who had received standard radiochemotherapy, the addition of TTFields to maintenance temozolomide chemotherapy vs maintenance temozolomide alone, resulted in statistically significant improvement in progression-free survival and overall survival. These results are consistent with the previous interim analysis. clinicaltrials.gov Identifier: NCT00916409

Aging, Cellular Senescence, and Progressive Multiple Sclerosis

Aging is one of the most important risk factors for the development of several neurodegenerative diseases including progressive multiple sclerosis (MS). Cellular senescence (CS) is a key biological process underlying aging. Several stressors associated with aging and MS pathology, such as oxidative stress, mitochondrial dysfunction, cytokines and replicative exhaustion are known triggers of cellular senescence. Senescent cells exhibit stereotypical metabolic and functional changes, which include cell-cycle arrest and acquiring a pro-inflammatory phenotype secreting cytokines, growth factors, metalloproteinases and reactive oxygen species. They accumulate with aging and can convert neighboring cells to senescence in a paracrine manner. In MS, accelerated cellular senescence may drive disease progression by promoting chronic non-remitting inflammation, loss or altered immune, glial and neuronal function, failure of remyelination, impaired blood-brain barrier integrity and ultimately neurodegeneration. Here we discuss the evidence linking cellular senescence to the pathogenesis of MS and the putative role of senolytic and senomorphic agents as neuroprotective therapies in tackling disease progression. © Copyright © 2020 Papadopoulos, Magliozzi, Mitsikostas, Gorgoulis and Nicholas

Durability of Angiosperm Heartwood: The Importance of Extractives

Analysis of osage orange (Maclura pomifera) heartwood extractives showed that two compounds were present at much higher levels than previously reported, the flavanonol dihydromorin (2.51%) and the stilbene oxyresverauol (2.65%). All compounds present in osage orange heartwood that were tested bad low activity against wood-decaying fungi. The agar plate test showed no synergistic effect, but the soil block test using white-rot fungi suggested synergism. The high durability of osage orange heartwood may be due to the large amounts of oxyresveratrol and dihydromorin. High levels of one or two monomeric compounds may also explain the exceptionally good durability of black locust and red mulberry heartwood