Explore the vast range of titles available.

Background: Decompressive hemicraniectomy (DHC) after space-occupying strokes among patients older than 60 years has been shown to reduce mortality rates but at the cost of severe disability. There is an ongoing debate about what could be considered an acceptable outcome for these patients. Data about retrospective consent to the procedure after lengthy time periods are lacking. Methods: This study included 79 consecutive patients who underwent DHC during a 7.75-year period. Surviving patients were assessed for functional and psychological outcome, quality of life (QoL) and retrospective consent for the procedure. Patients younger than 60 years were compared with older patients. Results: Of our 79 patients, 44 were younger than 60 years (median 50 years, interquartile range (IQR) 19-59 years) and 35 were older (median 68 years, interquartile range 60-87 years). The 30-day mortality rate was higher for the older group, but the difference was not statistically significant. Functional outcome was significantly better in the younger group: 31% of the patients in this group vs. 10% in the older group had a modified Rankin Scale score of 0-3 (p = 0.046). The mean National Institutes of Health Stroke Scale score was 17 ± 14 for the younger group and 29 ± 15 for the older group (p = 0.002). On the 36-Item Short Form Health Survey, with the exception of the item ‘General health', the older group reported higher values for all items, with statistically significant differences between the 2 groups on the items ‘Role limitation emotional' (p = 0.0007) and ‘Vitality' (p = 0.02). In the younger group, 29% of patients retrospectively declined consent for DHC opposed to 0% of patients in the older group (p = 0.07). Conclusions: Despite impaired functional outcome after DHC, indicators of QoL and retrospective consent are higher for patients older than 60 years over the long term. This finding should be taken into account by those who counsel patients and caregivers with regard to this serious procedure.

Melanin, a light and free radical absorbing pigment, is produced in melanocyte cells that are found in skin, but also in hair follicles, eyes, the inner ear, heart, brain and other organs. Melanin synthesis is the result of a complex network of signaling and metabolic reactions. It therefore comes as no surprise that mutations in many of the genes involved are associated with various types of pigmentation diseases and phenotypes (‘pigmentation genes’). Here, we used bioinformatics tools to first reconstruct gene-disease/phenotype associations for all pigmentation genes. Next, we reconstructed protein–protein interaction (PPI) networks centered around pigmentation gene products (‘pigmentation proteins’) and supplemented the PPI networks with protein expression information obtained by mass spectrometry in a panel of melanoma cell lines (both pigment producing and non-pigment producing cells). The analysis provides a systems network representation of all genes/ proteins centered around pigmentation and melanin biosynthesis pathways (‘pigmentation network map’). Our work will enable the pigmentation research community to experimentally test new hypothesis arising from the pigmentation network map and to identify new targets for drug discovery.

Ras is a key switch controlling cell behavior. In the GTP-bound form, Ras interacts with numerous effectors in a mutually exclusive manner, where individual Ras–effectors are likely part of larger cellular (sub)complexes. The molecular details of these (sub)complexes and their alteration in specific contexts are not understood. Focusing on KRAS, we performed affinity purification (AP)–mass spectrometry (MS) experiments of exogenously expressed FLAG-KRAS WT and three oncogenic mutants (“genetic contexts”) in the human Caco-2 cell line, each exposed to 11 different culture media (“culture contexts”) that mimic conditions relevant in the colon and colorectal cancer. We identified four effectors present in complex with KRAS in all genetic and growth contexts (“context-general effectors”). Seven effectors are found in KRAS complexes in only some contexts (“context-specific effectors”). Analyzing all interactors in complex with KRAS per condition, we find that the culture contexts had a larger impact on interaction rewiring than genetic contexts. We investigated how changes in the interactome impact functional outcomes and created a Shiny app for interactive visualization. We validated some of the functional differences in metabolism and proliferation. Finally, we used networks to evaluate how KRAS–effectors are involved in the modulation of functions by random walk analyses of effector-mediated (sub)complexes. Altogether, our work shows the impact of environmental contexts on network rewiring, which provides insights into tissue-specific signaling mechanisms. This may also explain why KRAS oncogenic mutants may be causing cancer only in specific tissues despite KRAS being expressed in most cells and tissues.

Ras is a central cellular hub protein controlling multiple cell fates. How Ras interacts with a variety of potential effector proteins is relatively unexplored, with only some key effectors characterised in great detail. Here, we have used homology modelling based on X-ray and AlphaFold2 templates to build structural models for 54 Ras-effectors complexes. These models were used to estimate binding affinities using a supervised learning regressor. Furthermore, we systematically introduced Ras \"branch-pruning\" (or branchegetic) mutations to identify 200 interface mutations that affect the binding energy with at least one of the model structures. The impacts of these branchegetic mutants were integrated into a mathematical model to assess the potential for rewiring interactions at the Ras hub on a systems level. These findings have provided a quantitative understanding of Ras-effector interfaces and their impact on systems properties of a key cellular hub.Competing Interest StatementThe authors have declared no competing interest.Footnotes* Reorganized main and supplementary figures; updated Section \"Assessment of rewiring of Ras-effector interaction on a systems level\"; updated references* https://doi.org/10.5281/zenodo.7188727

Ras is a key switch controlling cell behavior. In the GTP-bound form, Ras interacts with numerous effectors in a mutually exclusive manner, where individual Ras-effectors are likely part of larger cellular (sub)complexes. The molecular details of these (sub)complexes and their alteration in specific contexts is not understood. Focusing on KRAS, we performed affinity purification (AP)-mass spectrometry (MS) experiments of exogenous expressed FLAG-KRAS WT and three oncogenic mutants (‘genetic contexts’) in the human Caco-2 cell line, each exposed to 11 different culture media (‘culture contexts’) that mimic conditions relevant in the colon and colorectal cancer. We identified four effectors present in complex with KRAS in all genetic and growth contexts (‘context-general effectors’). Seven effectors are found in KRAS complexes in only some contexts (‘context-specific effectors’). Analyzing all interactors in complex with KRAS per condition, we find that the culture contexts had a larger impact on interaction rewiring than genetic contexts. We investigated how changes in the interactome impact functional outcomes and created a shiny app for interactive visualization. We validated some of the functional differences in metabolism and proliferation. Finally, we used networks to evaluate how KRAS effectors are involved in the modulation of functions by random walk analyses of effector-mediated (sub)complexes. Altogether, our work shows the impact of environmental contexts on network rewiring, which provides insights into tissue-specific signaling mechanisms. This may also explain why KRAS oncogenic mutants may be causing cancer only in specific tissues despite KRAS being expressed in most cells and tissues.

We present a comprehensive review of the physics results obtained by the CDF and D0 collaborations up to summer 2014, with emphasis on those achieved in the Run II of the Tevatron collider which delivered a total integrated luminosity of ~10 fb-1 at sqrt{s}=1.96 TeV. The results are presented in six main physics topics: QCD, Heavy Flavor, Electroweak, Top quark, Higgs boson and searches for New Particles and Interactions. The characteristics of the accelerator, detectors, and the techniques used to achieve these results are also briefly summarized.