Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

Correction: Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Correction to: Leukemia https://doi.org/10.1038/s41375-022-01711-0, published online 22 October 202

Linking intrinsic scales of ecological processes to characteristic scales of biodiversity and functioning patterns

Ecology is a science of scale, which guides our description of both ecological processes and patterns, but we lack a systematic understanding of how process scale and pattern scale are connected. Recent calls for a synthesis between population ecology, community ecology, and ecosystem ecology motivate the integration of phenomena at multiple levels of organization. Furthermore, many studies leave out the scaling of a critical process: species interactions, which may be non-local through movement or foraging and must be distinguished from dispersal scales. Here, we use simulations to explore the consequences of three different process scales (species interactions, dispersal, and the environment) on emergent patterns of biodiversity, ecosystem functioning, and their relationship, in a spatially-explicit landscape and stable equilibrium setting. A major result of our study is that the spatial scales of dispersal and species interactions have opposite effects: a larger dispersal scale homogenizes spatial biomass patterns, while a larger interaction scale amplifies their heterogeneity. Interestingly, the specific scale at which dispersal and interaction scales begin to influence landscape patterns depends on the scale of environmental heterogeneity-in other words, the scale of one process allows important scales to emerge in other processes. This interplay between process scales, i.e., a situation where no single process dominates, can only occur when the environment is heterogeneous and the scale of dispersal small. Finally, contrary to our expectations, we observe that the spatial scale of ecological processes is more clearly reflected in landscape patterns (i.e., distribution of local outcomes) than in global patterns such as Species-Area Relationships or large-scale biodiversity-functioning relationships. Overall we conclude that long-range interactions often act differently and even in opposite ways to dispersal, and that the landscape patterns that emerge from the interplay of long-ranged interactions, dispersal and environmental heterogeneity are not well captured by often-used metrics like the Species-Area Relationship

Green Infrastructure and Urban Forests for BioCities: Strategic and Adaptive Management

Urban nature has played an important role in cities around the world since industrialisation in the 18th century. The responsibility for urban nature has since then primarily lied with local governments, however with no formal obligation to develop or manage such areas. A number of concepts and approaches have been suggested over past decades to address planning and management of urban nature, but to gain maximum benefit of urban nature in forms of e.g. Green Infrastructure and Urban Forests, there are still a number of generic challenges to be overcome. These challenges includes fragmented organizational structures leading to disconnections between planning and management. Also governance related dimensions are often perceived as limiting factors for the improvement of urban nature. This chapter describes approaches to future management of Biocities in forms of Strategic Management and Adaptive Management, while also introducing new governance approaches. Three cases exemplifies novel local government approaches to inclusive governance and management of the urban nature—the future BioCities

Clinical Laboratory Analysis of Immunoglobulin Heavy Chain Variable Region Genes for Chronic Lymphocytic Leukemia Prognosis

Chronic lymphocytic leukemia (CLL) is the most common leukemia affecting adults in the western world. The clinical course of CLL is highly variable: cases that express mutated immunoglobulin heavy chain variable regions (IgVH) typically have a more indolent clinical course compared with those with unmutated IgVH. The use of the VH3-21 variable region has also been found to confer a poor prognosis, independent of mutation status. Here we describe an assay for the identification of the expressed VH segment and its mutation status in CLL. This test uses whole blood-derived RNA and PCR primers annealing to the leader regions and the joining region segments. This approach allows more accurate determination of the IgVH mutation status relative to using framework region specific VH primers. An additional primer specific for the leader region of the VH3-21 segment is described and is shown to be necessary to identify this diagnostically important variable region. We successfully analyzed 99 of 103 samples, including five expressing the VH3-21 variable region. Approximately 5% of cases had complement determining region 3 sequences similar to previously reported cases, and overrepresentation of the VH1-69 segment was observed among unmutated cases. These results confirm the proper functioning and high success rate of this valuable prognostic for CLL designed for the use in a clinical laboratory setting