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Plastic products contain complex mixtures of chemical compounds that are incorporated into polymers to improve material properties. Besides the intentional chemical additives, other compounds including residual monomers and non-intentionnaly added substances (NIAS) as well as sorbed pollutants are usually also present in aged plastic. Since most of these substances are only loosely bound to the polymer via non-covalently interactions, i.e., van der Waals forces, they may leach to the surrounding environment. Although there is increasing knowledge about toxicity of weathered plastic to aquatic organisms, only little is known about how plastic associated chemicals affect human health. Seafood consumption is one of the routes of human exposure to microplastics. The aim of this study was to evaluate the ability of naturally aged plastic associated chemicals to induce harmful effects to human health via the consumption of MP-contaminated seafood. Human colorectal adenocarcinoma Caco-2 and human hepatocyte carcinoma HepG2 cells were selected as model of the colon and liver cells respectively. They are known for their high capacity to metabolize organic contaminants. Both cell lines were exposed to DMSO extracts of different plastics to investigate the effects of chemicals on cell viability, oxidative stress induction and genotoxicity. In addition, the estrogenic effects of DMSO-extracts were evaluated using an estrogen-dependent reporter gene assay in T47D-Kbluc human breast cancer cells. Chemical profiles of the DMSO extracts were polymer-dependent, with polyvinyl chloride (PVC) highly contaminated with metals while polypropylene (PP) contained the lowest concentration of metals. Organic pollutants, including polycyclic aromatic hydrocarbons, were mainly found in PVC, high density polyethylene (HDPE) and PP extracts, whereas other extracted plastics had less (PP) to no organic contamination (polyethylene terephthalate PET). PVC was the most toxic plastic inducing cytotoxicity for both cell lines. DNA damage was observed for Caco-2 cells exposure to HDPE, PVC and nylon. Reactive oxygen species were induced only with nylon extracts in intestinal cells. No toxicity was observed for PP and PET and none of the tested plastics had any estrogenic effect. Our results demonstrate that some environmental aged plastic material released a variety of known and unknown chemical compounds some of which are toxic in vitro and contribute to the knowledge on adverse human health effects of plastics.

Introduction: The Bacillus Calmette-Guérin (BCG) used as anti-tuberculous vaccine is also a well-known therapy for superficial urothelial cancer. Local or general side effects can occur, although it is generally well tolerated. Case: We present the case of a 65 year-old caucasian man consulting for gross hematuria and lower urinary tract symptoms. Magnetic resonance imaging (MRI) demonstrated a non-invasive urothelial carcinoma (NMIBC) and Prostate Imaging–Reporting and Data System (PIRADS) IV lesions. Transurethral resection of the bladder tumor revealed a non-invasive transitional cell carcinoma. Intravesical Bacillus Calmette Guerin (BCG) therapy was provided. After 6 intravesical instillations, the patient presented with prostato-epididymitis. Forthcoming BCG instillations were canceled, and cancer treatment was switched to epirubicine. Treatment with ethambutol, rifampicin and isoniazid was started with rapid resolution of the symptoms. Urinary and semen cultures grew Mycobacterium tuberculosis complex strain BCG. As prostate specific antigen (PSA) rose, prostate’s biopsies were performed showing extensive necrosis boarded by granulomas without signs of malignancy. Discussion: BCGitis is a rare complication in patients treated for non-invasive urothelial cancer. Several risk factors, local and systemic, should be considered prior to this immunotherapy. BCGitis (local or disseminated) or hypersensitivity reactions to BCG must be included in the differential diagnosis even if therapy was administered several years before the symptoms. Adequate treatment must be started as fast as possible to avoid serious complications.

Abstract To compare region of interest (ROI)-apparent diffusion coefficient (ADC) on diffusion-weighted imaging (DWI) measurements and Ki-67 proliferation index before and after neoadjuvant chemotherapy (NACT) for breast cancer. 55 women were enrolled in this prospective single-center study, with a final population of 47 women (49 cases of invasive breast cancer). ROI-ADC measurements were obtained on MRI before and after NACT and were compared to histological findings, including the Ki-67 index in the whole study population and in subgroups of “pathologic complete response” (pCR) and non-pCR. Nineteen percent of women experienced pCR. There was a significant inverse correlation between Ki-67 index and ROI-ADC before NACT (r = − 0.443, p = 0.001) and after NACT (r = − 0.614, p

Aberrant aggregation of the transactive response DNA-binding protein (TDP-43) is associated with several lethal neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal dementia. Cytoplasmic neuronal inclusions of TDP-43 are enriched in various fragments of the low-complexity C-terminal domain and are associated with different neurotoxicity. Here we dissect the structural basis of TDP-43 polymorphism using magic-angle spinning solid-state NMR spectroscopy in combination with electron microscopy and Fourier-transform infrared spectroscopy. We demonstrate that various low-complexity C-terminal fragments, namely TDP-13 (TDP-43300–414), TDP-11 (TDP-43300–399), and TDP-10 (TDP-43314–414), adopt distinct polymorphic structures in their amyloid fibrillar state. Our work demonstrates that the removal of less than 10% of the low-complexity sequence at N- and C-termini generates amyloid fibrils with comparable macroscopic features but different local structural arrangement. It highlights that the assembly mechanism of TDP-43, in addition to the aggregation of the hydrophobic region, is also driven by complex interactions involving low-complexity aggregation-prone segments that are a potential source of structural polymorphism.

Objective: To assess tumor response with diffusion-weighted MRI (DW-MRI) after a short preoperative radiotherapy in early-stage breast cancer (BCa). Materials and Methods: This was a prospective, single-center pilot study. 3T-MRI were performed before and after radiotherapy. The longest diameter (LD) and the apparent diffusion coefficient (ADC) value of a region of interest (ROI) of the tumors were recorded. Histopathology and immunohistochemistry, including the Ki-67 index of the core biopsy and of the surgical specimen, were the reference standards. Results: Nineteen patients with 22 early-stage BCa were included. The mean ROI ADC value was 1.093 ± 0.278 × 10-3 mm2/s before radiotherapy and 1.490 ± 0.429 × 10-3 mm2/s (p-value < 0.001) after radiotherapy. The Ki-67 index was 9.2 ± 9.1% at the percutaneous biopsy before radiotherapy and 4.9 ± 7.5% (p-value = 0.005) after radiotherapy at the surgical specimen. After neoadjuvant radiotherapy, a 4.7% decrease in LD and a 36.3% increase in ROI-ADC of the tumors were measured at MRI and a 46.7% decrease in Ki-67 index was observed at histology of the surgical specimen in comparison with the percutaneous core biopsy. Conclusion: In early-stage BCa, a significant increase in ROI-ADC at DWI and a significant decrease in Ki-67 index were observed after a short preoperative radiotherapy, suggesting early tumor response.

Abstract In Granulomatosis with polyangiitis (GPA), involvement of the peripheral nervous system is frequent but its occurrence as an initial presentation is unusual. This case highlights the importance of this occurrence to permit an early diagnosis. Moreover, GPA started after a coronavirus disease 2019 infection and could have been induced by this.

The islet amyloid polypeptide (IAPP) is the main constituent of the amyloid fibrils found in the pancreas of type 2 diabetes patients. The aggregation of IAPP is known to cause cell death, where the cell membrane plays a dual role: being a catalyst of IAPP aggregation and being the target of IAPP toxicity. Using ATR-FTIR spectroscopy, transmission electron microscopy, and molecular dynamics simulations we investigate the very first molecular steps following IAPP binding to a lipid membrane. In particular, we assess the combined effects of the charge state of amino-acid residue 18 and the IAPP-membrane interactions on the structures of monomeric and aggregated IAPP. Distinct IAPP-membrane interaction modes for the various IAPP variants are revealed. Membrane binding causes IAPP to fold into an amphipathic α-helix, which in the case of H18K-, and H18R-IAPP readily moves beyond the headgroup region. For all IAPP variants but H18E-IAPP, the membrane-bound helix is an intermediate on the way to amyloid aggregation, while H18E-IAPP remains in a stable helical conformation. The fibrillar aggregates of wild-type IAPP and H18K-IAPP are dominated by an antiparallel β-sheet conformation, while H18R- and H18A-IAPP exhibit both antiparallel and parallel β-sheets as well as amorphous aggregates. Our results emphasize the decisive role of residue 18 for the structure and membrane interaction of IAPP. This residue is thus a good therapeutic target for destabilizing membrane-bound IAPP fibrils to inhibit their toxic actions.

Due to an aging population, neurodegenerative diseases such as Alzheimer’s disease (AD) have become a major health issue. In the case of AD, Aβ1–42 peptides have been identified as one of the markers of the disease with the formation of senile plaques via their aggregation, and could play a role in memory impairment and other tragic syndromes associated with the disease. Many studies have shown that not only the morphology and structure of Aβ1–42 peptide assembly are playing an important role in the formation of amyloid plaques, but also the interactions between Aβ1–42 and the cellular membrane are crucial regarding the aggregation processes and toxicity of the amyloid peptides. Despite the increasing amount of information on AD associated amyloids and their toxicity, the molecular mechanisms involved still remain unclear and require in-depth investigation at the local scale to clearly decipher the role of the sequence of the amyloid peptides, of their secondary structures, of their oligomeric states, and of their interactions with lipid membranes. In this original study, through the use of Atomic Force Microscopy (AFM) related-techniques, high-speed AFM and nanoInfrared AFM, we tried to unravel at the nanoscale the link between aggregation state, structure and interaction with membranes in the amyloid/membrane interaction. Using three mutants of Aβ peptides, L34T, oG37C, and WT Aβ1–42 peptides, with differences in morphology, structure and assembly process, as well as model lipidic membranes whose composition and structure allow interactions with the peptides, our AFM study coupling high spatial and temporal resolution and nanoscale structure information clearly evidences a local correlation between the secondary structure of the peptides, their fibrillization kinetics and their interactions with model membranes. Membrane disruption is associated to small transient oligomeric entities in the early stages of aggregation that strongly interact with the membrane, and present an antiparallel β-sheet secondary structure. The strong effect on membrane integrity that exists when these oligomeric Aβ1–42 peptides interact with membranes of a particular composition could be a lead for therapeutic studies.

Purpose: To show that a local event can have an international reputation.Design / methodology / approach: We will see through the analysis of the routes, the organization of the event and the proposed animations how much Angers velo vintage can have at international and local levelResearch and practical limitations / implications: We will rely solely on published news articles and researches published.

Antimicrobial peptides can be used as therapeutic agents against cancer cells. Warnericin RK and derivatives (WarnG20D and WarnF14V) were tested on various, solid tumor or leukemia, cancer cells. These peptides appeared to be cytotoxic on all the cell types tested, cancerous as well healthy, but very interestingly displayed no deleterious effect on healthy mononuclear cells. The mode of action of the peptide was proposed to be membranolytic, using chemical Raman imaging. Addition of peptide induced a large disorganization of the membrane leading to the loss of the content of inner compartments of Jurkat cell, whereas no effect was observed on the healthy mononuclear cells. The less hemolytic peptides WarnG20D and WarnF14V could be good candidates for the leukemia treatment.

Amyloid beta (Aβ) peptides produced by APP cleavage are central to the pathology of Alzheimer's disease. Despite widespread interest in this issue, the relationship between the auto-assembly and toxicity of these peptides remains controversial. One intriguing feature stems from their capacity to form anti-parallel ß-sheet oligomeric intermediates that can be converted into a parallel topology to allow the formation of protofibrillar and fibrillar Aβ. Here, we present a novel approach to determining the molecular aspects of Aß assembly that is responsible for its in vivo toxicity. We selected Aß mutants with varying intracellular toxicities. In vitro, only toxic Aß (including wild-type Aß42) formed urea-resistant oligomers. These oligomers were able to assemble into fibrils that are rich in anti-parallel ß-sheet structures. Our results support the existence of a new pathway that depends on the folding capacity of Aß .

Huntington disease (HD) is associated with early and severe damage to the basal ganglia and particularly the striatum. We investigated cortico-striatal connectivity modifications occurring in HD patients using a novel approach which focuses on the projection of the connectivity profile of the basal ganglia onto the cortex. This approach consists in computing, for each subcortical structure, surface connectivity measures representing its strength of connections to the cortex and comparing these measures across groups. In this study, we focused on Huntington disease as an application of this new approach. First, surface cortico-striatal connectivity measures of a group of healthy subjects were averaged in order to infer the "normal" connectivity profile of the striatum to the cortex. Second, a statistical analysis was performed from the surface connectivity measures of healthy subjects and HD patients in order to detect the cortical gyri presenting altered cortico-striatal connectivity in HD. Lastly, percentage differences of connectivity between healthy subjects and patients were inferred, for each nucleus of the striatum, from the connectivity measures of the cortical gyri presenting a significant connectivity difference between the two groups. These percentage differences characterize the axonal disruptions between the striatum and the cortex occurring in HD. We found selective region-specific degeneration of cortical connections predominating for associative and primary sensorimotor connections and with relative preservation of limbic connections. Our method can be used to infer novel connectivity-based markers of HD pathological process.

REF (Hevb1) and SRPP (Hevb3) are two major components of Hevea brasiliensis latex, well known for their allergenic properties. They are obviously taking part in the biosynthesis of natural rubber, but their exact function is still unclear. They could be involved in defense/stress mechanisms after tapping or directly acting on the isoprenoid biosynthetic pathway. The structure of these two proteins is still not described. In this work, it was discovered that REF has amyloid properties, contrary to SRPP. We investigated their structure by CD, TEM, ATR-FTIR and WAXS and neatly showed the presence of β-sheet organized aggregates for REF, whereas SRPP mainly fold as a helical protein. Both proteins are highly hydrophobic but differ in their interaction with lipid monolayers used to mimic the monomembrane surrounding the rubber particles. Ellipsometry experiments showed that REF seems to penetrate deeply into the monolayer and SRPP only binds to the lipid surface. These results could therefore clarify the role of these two paralogous proteins in latex production, either in the coagulation of natural rubber or in stress-related responses. To our knowledge, this is the first report of an amyloid formed from a plant protein. This suggests also the presence of functional amyloid in the plant kingdom.