SUMMARY Recent research has expanded our understanding of microbial community assembly. However, the field of community ecology is inaccessible to many microbial ecologists because of inconsistent and often confusing terminology as well as unnecessarily polarizing debates. Thus, we review recent literature on microbial community assembly, using the framework of Vellend (Q. Rev. Biol. 85 :183–206, 2010) in an effort to synthesize and unify these contributions. We begin by discussing patterns in microbial biogeography and then describe four basic processes (diversification, dispersal, selection, and drift) that contribute to community assembly. We also discuss different combinations of these processes and where and when they may be most important for shaping microbial communities. The spatial and temporal scales of microbial community assembly are also discussed in relation to assembly processes. Throughout this review paper, we highlight differences between microbes and macroorganisms and generate hypotheses describing how these differences may be important for community assembly. We end by discussing the implications of microbial assembly processes for ecosystem function and biodiversity.
The incidence of many cancer types is significantly reduced in individuals with Down syndrome1–4 and it is proposed that this broad cancer protection is conferred by the elevated expression of one or more of the 231 supernumerary genes on the extra copy of chromosome 21. One such gene is the Down syndrome candidate region-1 (Dscr1, RCAN1), which encodes a protein that suppresses vascular endothelial growth factor (VEGF)-mediated angiogenic signalling via the calcineurin pathway5–10. Here we show that DSCR1 is elevated in Down syndrome individuals and a mouse model of Down syndrome. Further, we show that the modest elevation in expression afforded by a single extra transgenic copy of Dscr1 is sufficient to confer significant suppression of tumor growth in mice and that such resistance is a consequence of a deficit in tumor angiogenesis arising from suppression of the calcineurin pathway. We also provide evidence that attenuation of calcineurin activity by DSCR1 together with another chromosome 21 gene DYRK1A, may be sufficient to dramatically diminish angiogenesis. These data provide a mechanism for the reduced cancer incidence in Down syndrome and identifies the calcineurin signalling pathway and its regulators DSCR1 and DYRK1A as potential therapeutic targets in cancers arising in all individuals.
Factors associated with durable remission after CD19 chimeric antigen receptor (CAR)-modified T-cell immunotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) have not been identified. We report multivariable analyses of factors affecting response and progression-free survival (PFS) in patients with aggressive NHL treated with cyclophosphamide and fludarabine lymphodepletion followed by 2 × 106 CD19-directed CAR T cells/kg. The best overall response rate was 51%, with 40% of patients achieving complete remission. The median PFS of patients with aggressive NHL who achieved complete remission was 20.0 months (median follow-up, 26.9 months). Multivariable analysis of clinical and treatment characteristics, serum biomarkers, and CAR T-cell manufacturing and pharmacokinetic data showed that a lower pre-lymphodepletion serum lactate dehydrogenase (LDH) level and a favorable cytokine profile, defined as serum day 0 monocyte chemoattractant protein-1 (MCP-1) and peak interleukin-7 (IL-7) concentrations above the median, were associated with better PFS. MCP-1 and IL-7 concentrations increased after lymphodepletion, and higher intensity of cyclophosphamide and fludarabine lymphodepletion was associated with higher probability of a favorable cytokine profile. PFS was superior in patients who received high-intensity lymphodepletion and achieved a favorable cytokine profile compared with those who received the same intensity of lymphodepletion without achieving a favorable cytokine profile. Even in high-risk patients with pre-lymphodepletion serum LDH levels above normal, a favorable cytokine profile after lymphodepletion was associated with a low risk of a PFS event. Strategies to augment the cytokine response to lymphodepletion could be tested in future studies of CD19 CAR T-cell immunotherapy for aggressive B-cell NHL. This trial was registered at www.clinicaltrials.gov as #NCT01865617.
Plants of the Cannabis genus are the only prolific producers of phytocannabinoids, compounds that strongly interact with the evolutionarily ancient endocannabinoid receptors shared by most bilaterian taxa. For millennia, the plant has been cultivated not only for these compounds, but also for food, rope, paper, and clothing. Today, specialized varieties yielding high-quality textile fibers, nutritional seed oil, or high cannabinoid content are cultivated across the globe. However, the genetic identities and histories of these diverse populations remain largely obscured. We analyzed the nuclear genomic diversity among 340 Cannabis varieties, including fiber and seed oil hemp, high cannabinoid drug-types, and feral populations. These analyses demonstrate the existence of at least three major groups of diversity with European hemp varieties more closely related to narrow leaflet drug-types (NLDTs) than to broad leaflet drug-types (BLDTs). The BLDT group appears to encompass less diversity than the NLDT, which reflects the larger geographic range of NLDTs, and suggests a more recent origin of domestication of the BLDTs. As well as being genetically distinct, hemp, NLDT, and BLDT genetic groups produce unique cannabinoid and terpenoid content profiles. This combined analysis of population genomic and trait variation informs our understanding of the potential uses of different genetic variants for medicine and agriculture, providing valuable insights and tools for a rapidly emerging valuable industry.
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