Sensitivity of the S1 neuronal calcium network to insulin and Bay‐K 8644 in vivo: Relationship to gait,motivation, and aging processes

Neuronal hippocampal Ca²⁺ dysregulation is a critical component of cognitive decline in brain aging and Alzheimer''s disease and is suggested to impact communication and excitability through the activation of a larger after hyperpolarization. However, few studies have tested for the presence of Ca²⁺ dysregulation in vivo, how it manifests, and whether it impacts network function across hundreds of neurons. Here, we tested for neuronal Ca²⁺ network dysregulation in vivo in the primary somatosensory cortex (S1) of anesthetized young and aged male Fisher 344 rats using single‐cell resolution techniques. Because S1 is involved in sensory discrimination and proprioception, we tested for alterations in ambulatory performance in the aged animal and investigated two potential pathways underlying these central aging‐ and Ca²⁺‐dependent changes. Compared to young, aged animals displayed increased overall activity and connectivity of the network as well as decreased ambulatory speed. In aged animals, intranasal insulin (INI) increased network synchronicity and ambulatory speed. Importantly, in young animals, delivery of the L‐type voltage‐gated Ca²⁺ channel modifier Bay‐K 8644 altered network properties, replicating some of the changes seen in the older animal. These results suggest that hippocampal Ca²⁺ dysregulation may be generalizable to other areas, such as S1, and might engage modalities that are associated with locomotor stability and motivation to ambulate. Further, given the safety profile of INI in the clinic and the evidence presented here showing that this central dysregulation is sensitive to insulin, we suggest that these processes can be targeted to potentially increase motivation and coordination while also reducing fall frequency with age.     

Conspecific plant–soil feedback scales with population size in Lobelia siphilitica (Lobeliaceae)

Plant–soil interactions directly affect plant success in terms of establishment, survival, growth and reproduction. Negative plant–soil feedback on such traits may therefore reduce the density and abundance of plants of a given species at a given site. Furthermore, if conspecific feedback varies among population sites, it could help explain geographic variation in plant population size. We tested for among-site variation in conspecific plant–soil feedback in a greenhouse experiment using seeds and soils from 8 natural populations of Lobelia siphilitica hosting 30–330 plants. The first cohort of seeds was grown on soil collected from each native site, while the second cohort was grown on the soil conditioned by the first. Our goal was to distinguish site-specific effects mediated by biotic and/or abiotic soil properties from those inherent in seed sources. Cohort 1 plants grown from seeds produced in small populations performed better in terms of germination, growth, and survival compared to plants produced in large populations. Plant performance decreased substantially between cohorts, indicating strong negative feedback. Most importantly, the strength of negative feedback scaled linearly (i.e., was less negative) with increasing size of the native plant population, particularly for germination and survival, and was better explained by soil- rather than seed-source effects. Even with a small number of sites, our results suggest that the potential for negative plant–soil feedback varies among populations of L. siphilitica, and that small populations were more susceptible to negative feedback. Conspecific plant–soil feedback may contribute to plant population size variation within a species’ native range.     

Shifts of bacteriochlorophyll and carotenoid absorption bands linked to cytochrome c-555 photooxidation in Chromatium

Shifts in the absorption bands of bacteriochlorophyll and carotenoids in Chromatium vinosum chromatophores were measured after short actinic flashes, under various conditions. The amplitude of the bacteriochlorophyll band shift correlated well with the amount of cytochrome c-555 that was oxidized by P₈₇₀⁺ after a flash. No bacteriochlorophyll band shift appeared to accompany the photooxidation of P₈₇₀ itself, nor the oxidation of cytochrome c-552 by P₈₇₀⁺. The carotenoid band shift also correlated with cytochrome c-555 photooxidation, although a comparatively small carotenoid shift did occur at high redox potentials that permitted only P₈₇₀ oxidation.

The results explain earlier observations on infrared absorbance changes that had suggested the existence of two different photochemical systems in Chromatium. A single photochemical system accounts for all of the absorbance changes.

Previous work has shown that the photooxidations of P₈₇₀ and cytochrome c-555 cause similar changes in the electrical charge on the chromatophore membrane. The specific association of the band shifts with cytochrome c-555 photooxidation therefore argues against interpretations of the band shifts based on a light-induced membrane potential.     

SIRT1 Activation by Small Molecules: KINETIC AND BIOPHYSICAL EVIDENCE FOR DIRECT INTERACTION OF ENZYME AND ACTIVATOR?

SIRT1 is a protein deacetylase that has emerged as a therapeutic target for the development of activators to treat diseases of aging. SIRT1-activating compounds (STACs) have been developed that produce biological effects consistent with direct SIRT1 activation. At the molecular level, the mechanism by which STACs activate SIRT1 remains elusive. In the studies reported herein, the mechanism of SIRT1 activation is examined using representative compounds chosen from a collection of STACs. These studies reveal that activation of SIRT1 by STACs is strongly dependent on structural features of the peptide substrate. Significantly, and in contrast to studies reporting that peptides must bear a fluorophore for their deacetylation to be accelerated, we find that some STACs can accelerate the SIRT1-catalyzed deacetylation of specific unlabeled peptides composed only of natural amino acids. These results, together with others of this study, are at odds with a recent claim that complex formation between STACs and fluorophore-labeled peptides plays a role in the activation of SIRT1 (Pacholec, M., Chrunyk, B., Cunningham, D., Flynn, D., Griffith, D., Griffor, M., Loulakis, P., Pabst, B., Qiu, X., Stockman, B., Thanabal, V., Varghese, A., Ward, J., Withka, J., and Ahn, K. (2010) J. Biol. Chem. 285, 8340–8351). Rather, the data suggest that STACs interact directly with SIRT1 and activate SIRT1-catalyzed deacetylation through an allosteric mechanism.     

Variation in the methods leads to variation in the interpretation of biodiversity–ecosystem multifunctionality relationships

生物多样性常常和生态系统多功能性(生态系统同时提供多个生态系统功能的能力)正相关。然而,生物多样性与生态系统多功能性的关系是否依赖于生态系统功能的数目有诸多争议。其中,生物多样性对生态系统多功能性的影响或许不随生态系统功能数目的变化而变化,或者随生态系统功能数目的增多而增强。我们期望通过研究不同生态系统多功能性指数的统计原理来解决这些争议。 我们使用了模型模拟和一系列来自不同空间尺度(从局域到全球)和不同生物群系(温带和高寒草地、森林和干旱地)的经验数据。我们回顾了量化生态系统多功能性的三种方法,包括平均值法、加和法和阈值法。我们发现随着生态系统功能数目的增加,生物多样性与生态系统多功能性的关系要么不变,要么增强。这些结果可由平均和加和的多功能性指数的统计原理来解释。具体来讲,当利用生态系统功能的平均值计算多功能性指数时,由于多样性对多功能性的效应等于多样性对单个生态系统功能效应的平均值,所以不会随生态系统功能数目的变化而变化。同样的道理,当利用单个生态系统的加和值计算多功能性指数时,多样性的效应会随着生态系统功能数目的增加而增强。我们提出了一个改进的多功能性指数,将平均或加和多功能性指数转化为标准化的多功能性指数, 以便于对不同研究的结果进行比较。此外,我们提出了基于变量数值范围的标准化方法来解决阈值法的数学假象问题(多样性效应随生态系统功能数目的增加而增强)。我们的研究结果表明,量化多功能性指数的方法不同,结果也不同。因此,有必要加深对不同方法数理基础的理解。而标准化的多功能性指数为比较不同研究中的生物多样性与生态系统多功能性的关系提供了有效的方法。