Too much of a good thing

Culture of primary lymphocytes at physiological oxygen levels better maintains intracellular redox state.     

Too much of a good thing: light can be bad for photosynthesis.

Even though light is the ultimate substrate for photosynthetic energy conversion, it can also harm plants. This toxicity is targeted to the water-splitting photosystem II and leads to damage and degradation of the reaction centre D1-polypeptide. The degradation of this very important protein appears to be a direct consequence of photosystem II chemistry involving highly oxidizing radicals and toxic oxygen species. The frequency of this damage is relatively low under normal conditions but becomes a significant problem for the plant with increasing light intensity, especially when combined with other environmental stress factors. However, the plant survives this photoinhibition through an efficient repair system which involves an autoproteolytic activity of the photosystem II complex, D1-polypeptide synthesis and reassembly of active complexes.     

Too much of a good thing: resource provisioning alters infectious disease dynamics in wildlife

Provisioning of abundant food resources in human-altered landscapes can have profound effects on wildlife ecology, with important implications for pathogen transmission. While empirical studies have quantified the effects of provisioning on host behaviour and immunology, the net interactive effect of these components on host–pathogen dynamics is unknown. We use simple compartmental models to investigate how provisioning-induced changes to host demography, contact behaviour and immune defence influence pathogen invasion and persistence. We show that pathogen invasion success and equilibrium prevalence depend critically on how provisioning affects host immune defence and that moderate levels of provisioning can lead to drastically different outcomes of pathogen extinction or maximizing prevalence. These results highlight the need for further empirical studies to fully understand how provisioning affects pathogen transmission in urbanized environments.     

Too much of a good thing: the Prl-3 in p53's oyster

In this issue of Molecular Cell, Basak et al. (2008) identify Prl-3 as a p53-inducible gene acting in DNA damage-induced cell-cycle arrest. Both deletion and overexpression of Prl-3 can be cytostatic, adding to a growing list of genes whose expression must be carefully titrated for proper cell proliferation.     

Too much of a good thing: sea ice extent may have forced emperor penguins into refugia during the last glacial maximum

The relationship between population structure and demographic history is critical to understanding microevolution and for predicting the resilience of species to environmental change. Using mitochondrial DNA from extant colonies and radiocarbon‐dated subfossils, we present the first microevolutionary analysis of emperor penguins (Aptenodytes forsteri) and show their population trends throughout the last glacial maximum (LGM, 19.5–16 kya) and during the subsequent period of warming and sea ice retreat. We found evidence for three mitochondrial clades within emperor penguins, suggesting that they were isolated within three glacial refugia during the LGM. One of these clades has remained largely isolated within the Ross Sea, while the two other clades have intermixed around the coast of Antarctica from Adélie Land to the Weddell Sea. The differentiation of the Ross Sea population has been preserved despite rapid population growth and opportunities for migration. Low effective population sizes during the LGM, followed by a rapid expansion around the beginning of the Holocene, suggest that an optimum set of sea ice conditions exist for emperor penguins, corresponding to available foraging area.     

Too much of a good thing: the role of protein kinase CK2 in tumorigenesis and prospects for therapeutic inhibition of CK2

CK2 is a highly conserved protein serine/threonine kinase that is ubiquitously distributed in eukaryotes, constitutively active and has been implicated in multiple cellular functions, as well as in tumorigenesis and transformation. Elevated CK2 activity has been associated with the malignant transformation of several tissues and is associated with aggressive tumor behaviour. While the precise roles of CK2 in tumorigenesis remain incompletely understood, mounting evidence suggests a role for CK2 in the protection of cells from apoptosis via the regulation of tumor suppressor and oncogene activity. Consequently, CK2 has emerged as a potential therapeutic target, and strategies to inhibit CK2 have been ongoing in pre-clinical trials. This review will focus on published evidence highlighting the molecular mechanisms by which CK2 functions in the promotion of tumorigenesis, as well as review current strategies being used to inhibit CK2.     

The ACR20 and defining a threshold for response in rheumatic diseases: too much of a good thing

In the past 20 years great progress has been made in the development of multidimensional outcome measures (such as the Disease Activity Score and ACR20) to evaluate treatments in rheumatoid arthritis, a process disseminated throughout rheumatic diseases. These outcome measures have standardized the assessment of outcomes in trials, making it possible to evaluate and compare the efficacy of treatments. The methodologic advances have included the selection of pre-existing outcome measures that detected change in a sensitive fashion (in rheumatoid arthritis, this was the Core Set Measures). These measures were then combined into a single multidimensional outcome measure and such outcome measures have been widely adopted in trials and endorsed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) and regulatory agencies. The secular improvement in treatment for patients with rheumatoid arthritis has been facilitated in part by these major methodologic advancements. The one element of this effort that has not optimized measurement of outcomes nor made it easier to detect the effect of treatments is the dichotomization of continuous measures of response, creating responders and non-responder definitions (for example, ACR20 responders; EULAR good responders). Dichotomizing response sacrifices statistical power and eliminates variability in response. Future methodologic work will need to focus on improving multidimensional outcome measurement without arbitrarily characterizing some patients as responders while labeling others as non-responders.