Striking convergence in the mouthpart evolution of stream-living algae grazers

This scanning-electron microscopic study demonstrates the convergent evolution of the mouthparts of various herbivorous stream animals (insects from different orders, an isopod, snails, fish, and a tadpole) feeding on epilithic algal pastures. This food source is rich but is often difficult to harvest. Nevertheless, a large number of species can live on it because they have evolved highly specialized mouthparts. There are four functional problems that an algae grazer has to solve: the algae must be removed from the stone, they have to be collected and crushed, and a current shield is needed to prevent the water flow sweeping away the food. Among the 30 algae grazers examined in this study, a limited number of morphological solutions have been found for each of these adaptational problems. There are multiple evolutionary pathways for mouthpart adaptation and even closely related species have often evolved different types of tools for the same function. This refects the existence of a certain amount of evolutionary scope. Such freedom of evolution is present, however, only at the beginning of the adaptiogenesis of an algae grazer. Once one of the evolutionary pathways is taken, further improvement of the mouthparts is possible only by the refinement of the ‘chosen’ type of tools. The consequence of this is that a large number of astonishing convergences have occurred in algae grazers that have independently trodden the same evolutionary pathway.     

The new biology of ageing

Human life expectancy in developed countries has increased steadily for over 150 years, through improvements in public health and lifestyle. More people are hence living long enough to suffer age-related loss of function and disease, and there is a need to improve the health of older people. Ageing is a complex process of damage accumulation, and has been viewed as experimentally and medically intractable. This view has been reinforced by the realization that ageing is a disadvantageous trait that evolves as a side effect of mutation accumulation or a benefit to the young, because of the decline in the force of natural selection at later ages. However, important recent discoveries are that mutations in single genes can extend lifespan of laboratory model organisms and that the mechanisms involved are conserved across large evolutionary distances, including to mammals. These mutations keep the animals functional and pathology-free to later ages, and they can protect against specific ageing-related diseases, including neurodegenerative disease and cancer. Preliminary indications suggest that these new findings from the laboratory may well also apply to humans. Translating these discoveries into medical treatments poses new challenges, including changing clinical thinking towards broad-spectrum, preventative medicine and finding novel routes to drug development.     

The vitamin D metabolome: An update on analysis and function

Current understanding of vitamin D tends to be focussed on the measurement of the major circulating form 25‐hydroxyvitamin D3 (25OHD3) and its conversion to the active hormonal form, 1α,25‐dihydroxyvitamin D3 (1α,25(OH)₂D3) via the enzyme 25‐hydroxyvitamin D‐1α‐hydroxylase (CYP27B1). However, whilst these metabolites form the endocrine backbone of vitamin D physiology, it is important to recognise that there are other metabolic and catabolic pathways that are now recognised as being crucially important to vitamin D function. These pathways include C3‐epimerization, CYP24A1 hydroxylase, CYP11A1 alternative metabolism of vitamin D3, and phase II metabolism. Endogenous metabolites beyond 25OHD3 are usually present at low endogenous levels and may only be functional in specific target tissues rather than in the general circulation. However, the technologies available to measure these metabolites have also improved, so that measurement of alternative vitamin D metabolic pathways may become more routine in the near future. The aim of this review is to provide a comprehensive overview of the various pathways of vitamin D metabolism, as well as describe the analytical techniques currently available to measure these vitamin D metabolites.     

Oxygen Radicals Acting as Chemical Messengers: A Hypothesis

Based on a critical reappraisal of the reactions of radicals in a biological milieu, a hypothesis is proposed according to which superoxide anion radicals act as biological messengers rather than as mediators or precursors of cellular damage under oxidative stress conditions.     

NP7 protects from cell death induced by oxidative stress in neuronal and glial midbrain cultures from parkin null mice

Parkin mutations produce Parkinson’s disease (PD) in humans and nigrostriatal dopamine lesions related to increased free radicals in mice. We examined the effects of NP7, a synthetic, marine derived, free radical scavenger which enters the brain, on H₂O₂ toxicity in cultured neurons and glia from wild-type (WT) and parkin null mice (PK-KO).NP7, 5-10 μM, prevented the H₂O₂ induced apoptosis and necrosis of midbrain neuronal and glial cultures from WT and PK-KO mice. NP7 suppressed microglial activation and the H₂O₂ induced drop-out of dopamine neurons_. Furthermore, NP7 prevented the increased phosphorylation of ERK and AKT induced by H₂O₂. NP7 may be a promising neuroprotector against oxidative stress in PD.     

溶血磷脂酸在皮肤损伤疾病中的作用及其分子机制

皮肤作为人体最大器官覆盖于全身,能阻挡有害物质的侵入,保护人体内环境稳态,参与人体代谢过程。皮肤损伤、炎症和纤维化等,都会导致皮肤屏障功能的减退,影响正常的生命活动。溶血磷脂酸(lysophosphatidic acid,LPA)是十分活跃的磷脂信号分子,参与多种生理和病理生理过程。LPA是维持体内平衡所必需的生物活性脂质介质,在皮肤中通过不同的信号通路发挥多功能磷脂信使作用。本文综述了皮肤中溶血磷脂酸受体(lysophosphatidic acid receptor,LPA1-6)及其细胞信号通路的作用及机制,综述了LPA在皮肤创面愈合、皮肤瘢痕、皮肤黑色素瘤、硬皮病、皮肤瘙痒、过敏性皮炎、皮肤屏障、皮肤疼痛,皮肤毛发生长中的作用及分子机制,有助于了解LPA在皮肤中的生理和病理生理作用。深入研究LPA的作用机制将有助于挖掘其在皮肤治疗中的作用,开发以LPA为靶点的药物。     

Diosgenin inhibits superoxide generation in FMLP-activated mouse neutrophils via multiple pathways

Abstract

Diosgenin possesses anti-inflammatory and anticancer properties. Activated neutrophils produce high concentrations of the superoxide anion which is involved in the pathophysiology of inflammation-related diseases and cancer. In the present study, the inhibitory effect and possible mechanisms of diosgenin on superoxide generation were investigated in mouse bone marrow neutrophils. Diosgenin potently and concentration-dependently inhibited the extracellular and intracellular superoxide anion generation in Formyl-Met-Leu-Phe (FMLP)- activated neutrophils, with IC₅₀ values of 0.50 ± 0.08 μM and 0.66 ± 0.13 μM, respectively. Such inhibition was not mediated by scavenging the superoxide anion or by a cytotoxic effect. Diosgenin inhibited the phosphorylation of p47phox and membrane translocation of p47phox and p67phox, and thus blocking the assembly of nicotinamide adenine dinucleotide phosphate oxidase. Moreover, cellular cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) expression were also effectively increased by diosgenin. It attenuated FMLP-induced increase of phosphorylation of cytosolic phospholipase A (cPLA₂), p21-activated kinase (PAK), Akt, p38 mitogen-activated protein kinase (p38MAPK), extracellular signal-regulated kinase (ERK1/2), and c-Jun N-terminal kinase (JNK). Our data indicate that diosgenin exhibits inhibitory effects on superoxide anion production through the blockade of cAMP, PKA, cPLA₂, PAK, Akt and MAPKs signaling pathways. The results may explain the clinical implications of diosgenin in the treatment of inflammation-related disorders.