Functional approach to the electromagnetic response function: the Longitudinal Channel

In this paper we address the (charge) longitudinal electromagnetic response for a homogeneous system of nucleons interacting via meson exchanges in the functional framework. This approach warrants consistency if the calculation is carried on order-by-order in the mesonic loop expansion with RPA-dressed mesonic propagators. At the 1-loop order and considering pion, rho and omega exchanges we obtain a quenching of the response, in line with the experimental results.Comment: RevTeX, 18 figures available upon request - to be published in Physical Review

Fermion propagators in space-time

The one- and the two-particle propagators for an infinite non-interacting Fermi system are studied as functions of space-time coordinates. Their behaviour at the origin and in the asymptotic region is discussed, as is their scaling in the Fermi momentum. Both propagators are shown to have a divergence at equal times. The impact of the interaction among the fermions on their momentum distribution, on their pair correlation function and, hence, on the Coulomb sum rule is explored using a phenomenological model. Finally the problem of how the confinement is reflected in the momentum distribution of the system's constituents is briefly addressed.Comment: 26 pages, 9 figures, accepted for publication on Phys. Rev.

Revisiting the role of GSK3, a modulator of innate immunity, in idiopathic inclusion body myositis

Idiopathic or sporadic inclusion body myositis (IBM) is the leading age-related (onset > 50 years of age) autoimmune muscular pathology, resulting in significant debilitation in affected individuals. Once viewed as primarily a degenerative disorder, it is now evident that much like several other neuro-muscular degenerative disorders, IBM has a major autoinflammatory component resulting in chronic inflammation-induced muscle destruction. Thus, IBM is now considered primarily an inflammatory pathology. To date, there is no effective treatment for sporadic inclusion body myositis, and little is understood about the pathology at the molecular level, which would offer the best hopes of at least slowing down the degenerative process. Among the previously examined potential molecular players in IBM is glycogen synthase kinase (GSK)-3, whose role in promoting TAU phosphorylation and inclusion bodies in Alzheimer’s disease is well known. This review looks to re-examine the role of GSK3 in IBM, not strictly as a promoter of TAU and Abeta inclusions, but as a novel player in the innate immune system, discussing some of the recent roles discovered for this well-studied kinase in inflammatory-mediated pathology

Singular Structure and Enhanced Friedel Oscillations in the Two-Dimensional Electron Gas

We calculate the leading order corrections (in $r_s$) to the static polarization $\Pi^{*}(q,0,)$, with dynamically screened interactions, for the two-dimensional electron gas. The corresponding diagrams all exhibit singular logarithmic behavior in their derivatives at $q=2 k_F$ and provide significant enhancement to the proper polarization particularly at low densities. At a density of $r_s=3$, the contribution from the leading order {\em fluctuational} diagrams exceeds both the zeroth order (Lindhard) response and the self-energy and exchange contributions. We comment on the importance of these diagrams in two-dimensions and make comparisons to an equivalent three-dimensional electron gas; we also consider the impact these finding have on $\Pi^{*}(q,0)$ computed to all orders in perturbation theory

Expression profiling of ANKRD1 in rhabdomyosarcoma cell lines

Introduction: Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in children and adolescents. Respecting the age of the patients and the tumor aggressiveness, investigation of the molecular mechanisms of RMS tumorigenesis is essential, most notably due to the possible identification of novel therapeutic targets. To contribute to a better understanding of the molecular pathology of RMS, we investigated ANKRD1 (ankyrin repeat domain 1) gene, considered a potential RMS diagnostic marker. The changes in its expression are related to carcinogenesis and resistance to chemotherapy in several types of tumors.EACR 2023: Innovative Cancer Science, 12-15 June 2023, Torino, Ital

Autophagic degradation of farnesylated prelamin A as a therapeutic approach to lamin-linked progeria

Farnesylated prelamin A is a processing intermediate produced in the lamin A maturation pathway. Accumulation of a truncated farnesylated prelamin A form, called progerin, is a hallmark of the severe premature ageing syndrome, Hutchinson-Gilford progeria. Progerin elicits toxic effects in cells, leading to chromatin damage and cellular senescence and ultimately causes skin and endothelial defects, bone resorption, lipodystrophy and accelerated ageing. Knowledge of the mechanism underlying prelamin A turnover is critical for the development of clinically effective protein inhibitors that can avoid accumulation to toxic levels without impairing lamin A/C expression, which is essential for normal biological functions. Little is known about specific molecules that may target farnesylated prelamin A to elicit protein degradation. Here, we report the discovery of rapamycin as a novel inhibitor of progerin, which dramatically and selectively decreases protein levels through a mechanism involving autophagic degradation. Rapamycin treatment of progeria cells lowers progerin, as well as wild-type prelamin A levels, and rescues the chromatin phenotype of cultured fibroblasts, including histone methylation status and BAF and LAP2α distribution patterns. Importantly, rapamycin treatment does not affect lamin C protein levels, but increases the relative expression of the prelamin A endoprotease ZMPSTE24. Thus, rapamycin, an antibiotic belonging to the class of macrolides, previously found to increase longevity in mouse models, can serve as a therapeutic tool, to eliminate progerin, avoid farnesylated prelamin A accumulation, and restore chromatin dynamics in progeroid laminopathies

Quasielastic Electron Scattering from Nuclei: Random-Phase vs. Ring Approximations

We investigate the extent to which the nuclear transverse response to electron scattering in the quasielastic region, evaluated in the random-phase approximation can be described by ring approximation calculations. Different effective interactions based on a standard model of the type g'+V_pi+V_rho are employed. For each momentum transfer, we have obtained the value of g'_0 permitting the ring response to match the position of the peak and/or the non-energy weighted sum rule provided by the random-phase approach has been obtained. It is found that, in general, it is not possible to reproduce both magnitudes simultaneously for a given g'_0 value.Comment: 7 pages, 4 Postscript figures, to appear in Physical Review

Genotype‐phenotype analysis of LMNA‐related diseases predicts phenotype‐selective alterations in lamin phosphorylation

Laminopathies are rare diseases associated with mutations in LMNA, which encodes nuclear lamin A/C. LMNA variants lead to diverse tissue‐specific phenotypes including cardiomyopathy, lipodystrophy, myopathy, neuropathy, progeria, bone/skin disorders, and overlap syndromes. The mechanisms underlying these heterogeneous phenotypes remain poorly understood, although post‐translational modifications, including phosphorylation, are postulated as regulators of lamin function. We catalogued all known lamin A/C human mutations and their associated phenotypes, and systematically examined the putative role of phosphorylation in laminopathies. In silico prediction of specific LMNA mutant‐driven changes to lamin A phosphorylation and protein structure was performed using machine learning methods. Some of the predictions we generated were validated via assessment of ectopically expressed wild‐type and mutant LMNA. Our findings indicate phenotype‐ and mutant‐specific alterations in lamin phosphorylation, and that some changes in phosphorylation may occur independently of predicted changes in lamin protein structure. Therefore, therapeutic targeting of phosphorylation in the context of laminopathies will likely require mutant‐ and kinase‐specific approaches.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155891/1/fsb220571.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155891/2/fsb220571_am.pd