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Decrease in the Permeability of Microcracked and Macrocracked Granite at Elevated Pressure and Temperature
No full textNavigating complex choices through legitimation: Narrative strategies in risk-reduction mastectomy decision-making among unaffected women with genetic risk for breast cancer in Switzerland
No full textFor unaffected women at high risk for developing breast cancer due to pathogenic variants in BRCA1 or BRCA2 (BRCA) genes, bilateral risk-reducing mastectomy (RRM) is an alternative to intensive surveillance. RRM reduces breast cancer risk but may generate additional health and psychosocial issues, making the choice between surveillance and RRM complex and personal. This grounded theory study explores how unaffected women carrying BRCA pathogenic variants engage in a decision-making process leading to the choice of undergoing RRM. Narrative data were collected in Switzerland through biographical interviews with 38 unaffected women carrying BRCA pathogenic variants. Participants had either undergone RRM or were planning the surgery in the future. Findings indicate that the decision to undergo RRM was influenced by femininity and body image, current life engagements, anticipation of surgery risks and outcomes, perception and acceptance of cancer risk, surveillance experiences, attitudes of healthcare providers and family, and financial considerations. These factors interacted, creating contradictions that made decision-making challenging. To navigate this uncertainty, women progressively built their decision through a triple process of making sense: framing RRM as an obligated, empowering and mundane choice. This sense-making process is described as a process of legitimation, through which women decide to undergo RRM and integrate it into their life trajectory, ensuring its acceptability for themselves and their social circles. The discussion provides insights into the legitimation process as a heuristic tool for exploring crucial choices in uncertainty and offers implications for healthcare providers assisting individuals in complex decision-making processes
Salt‐Compact Albumin as a New Pure Protein‐based Biomaterials: From Design to In Vivo Studies
No full textCurrent biodegradable materials are facing many challenges when used for the design of implantable devices because of shortcomings such as toxicity of crosslinking agents and degradation derivatives, limited cell adhesion, and limited immunological compatibility. Here, a class of materials built entirely of stable protein is designed using a simple protocol based on salt-assisted compaction of albumin, breaking with current crosslinking strategies. Salt-assisted compaction is based on the assembly of albumin in the presence of high concentrations of specific salts such as sodium bromide. This process leads, surprisingly, to water-insoluble handable materials with high preservation of their native protein structures and Young's modulus close to that of cartilage (0.86 MPa). Furthermore, these materials are non-cytotoxic, non-inflammatory, and in vivo implantations (using models of mice and rabbits) demonstrate a very slow degradation rate of the material with excellent biocompatibility and absence of systemic inflammation and implant failure. Therefore, these materials constitute promising candidates for the design of biodegradable scaffolds and drug delivery systems as an alternative to conventional synthetic degradable polyester materials.
Keywords: albumin; biodegradable materials; protein‐based materials; salt‐assisted compaction
Refining the deep sub-barrier 12C+12C fusion excitation function with the STELLA apparatus
No full textN -Heterocyclic carbene platinum complexes encapsulated in lipid particles: a novel strategy to target cancer cells and cancer stem cells in glioblastoma
No full textThe properties against cancer cells and glioblastoma stem cells of a series of platinum NHC complexes in lipid formulations are reported. As these organometallic compounds show very promising biological activities using conventional formulations, i.e. by solubilization in a DMSO/water system, the challenge for a therapeutic application is to be able to make them biocompatible while retaining this activity. Herein with the aim of eradicating cancer cells and cancer stem cells from glioblastoma, a disease in need of new therapies, we studied the encapsulation of platinum compounds in either liposome or lipid nanocapsule formulations and investigated the physical and chemical stability of the resulting nano-objects. It was then demonstrated that in these lipid formulations, platinum complexes retained their cytotoxic activity on both cancer cells and cancer stem cells. The best candidate, i.e. triphenylphosphonium-functionalized platinum-based complex, was then used for in vivo studies on mice using a U87-MG glioblastoma model, with significant results in slowing tumor growth, in particular when comparing to oxaliplatin. Another key strength of this study is the preservation of the compound's anti-cancer activity within a lipid-based formulation, eliminating the need for DMSO as a solvent. The findings of this study signify a major advance in the field, particularly in light of the expanding body of research on organometallic complexes conducted under conditions that preclude direct clinical applicability
Structure of the nucleosome-bound human BCL7A
No full textProteins of the BCL7 family (BCL7A, BCL7B, and BCL7C) are among the most recently identified subunits of the mammalian SWI/SNF chromatin
remodeler complex and are absent from the unicellular version of this complex. Their function in the complex is unknown, and very limited
structural information is available, despite the fact that they are mutated in several cancer types, most notably blood malignancies and hence
medically relevant. Here, using cryo-electron microscopy in combination with biophysical and biochemical approaches, we show that BCL7A
forms a stable, high-affinity complex with the nucleosome core particle (NCP) through binding of BCL7A with the acidic patch of the nucleosome
via an arginine anchor motif. This interaction is impaired by BCL7A mutations found in cancer. Further, we determined that BCL7A contributes to
the remodeling activity of the mSWI/SNF complex and we examined its function at the genomic level. Our findings reveal how BCL7 proteins
interact with the NCP and help rationalize the impact of cancer-associated mutations. By providing structural information on the positioning of
BCL7 on the NCP, our results broaden the understanding of the mechanism by which SWI/SNF recognizes the chromatin fiber
Combining dynamin 2 myopathy and neuropathy mutations rescues both phenotypes.
No full textMutations within a single gene can lead to diverse human genetic diseases affecting highly specialized tissues. Notably, dominant mutations in the DNM2 gene, encoding the mechanoenzyme dynamin, lead to distinct neuromuscular disorders: centronuclear myopathy (CNM) and Charcot-Marie-Tooth neuropathy (CMT). CNM is characterized by myofiber structural anomalies while CMT presents peripheral nerve defects, both culminating in muscle weakness and atrophy. Despite their shared genetic origin, the mechanisms driving these diseases remain elusive, and no cure is available. Here, we present in vitro assays underlining opposing effects of DNM2 mutations, gain-of-function in CNM and loss-of-function in CMT. In vivo, we explored the potential compensatory effects of CNM and CMT mutations by breeding Dnm2journal article2025 May 202025 05 20importe
