Oxidative stress is implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). In the present study, hepatic and plasma oxidative stress-related parameters were measured and correlated with clinical and histological findings in 31 NAFLD patients showing increased body mass index. Liver protein carbonyl content was enhanced by 403% in patients with steatosis (n=15) compared with control values (n=12), whereas glutathione content, superoxide dismutase (SOD) activity and the ferric reducing ability of plasma (FRAP) were decreased by 57%, 48% and 21% (P<0.05) respectively. No changes in microsomal p-nitrophenol hydroxylation and the total content of cytochrome P450 (CYP) or CYP2E1 were observed. Patients with steatohepatitis (n=16) exhibited protein carbonyl content comparable with that of controls, whereas glutathione content, SOD and catalase activities were decreased by 27%, 64% and 48% (P<0.05). In addition, FRAP values in patients with steatohepatitis were reduced by 33% and 15% (P<0.05) when compared with controls and patients with steatosis respectively, whereas p-nitrophenol hydroxylation (52%) and CYP2E1 content (142%) were significantly increased (P<0.05) compared with controls. It is concluded that oxidative stress is developed in the liver of NAFLD patients with steatosis and is exacerbated further in patients with steatohepatitis, which is associated with CYP2E1 induction. Substantial protein oxidation is followed by proteolysis of the modified proteins, which may explain the co-existence of a diminished antioxidant capacity and protein oxidation in the liver of patients with steatohepatitis.

miological studies have reported positive associations between the risk of coronary heart disease (CHD) and plasma fibrinogen levels. Fibrinogen is the major coagulation protein in blood by mass, the precursor of fibrin, and an important determinant of blood viscosity and platelet aggregation. [38][39][40][41] Because fibrinogen levels can be reduced considerably by lifestyle interventions that also affect levels of established risk factors (such as regular exercise, smoking cessation, and moderate alcohol consumption), there is interest in the possibility that measurement (or modification) of fibrinogen may help in disease prediction or prevention. [38][39][40]42 A meta-analysis of published data from 18 such studies, involving about 4000 CHD cases, indicated a relative risk of 1.8 (95% confidence interval [CI], 1.6-2.0) per 1-g/L increase in plasma fibrinogen level. 43 However, such analyses are not able to provide detailed assessments of the nature of any independent association of fibrinogen level with CHD or with other vascular and nonvascular outcomes. [43][44][45] This meta-analysis differs from previous analyses in several ways that should increase its reliability and scientific value. First, it is large and comprehensive: the data comprise 6944 first nonfatal myocardial infarction (MI) or stroke events and 13 210 deaths (cause-*The Authors/Writing Committee, Authors/Members, and Other Members of the Fibrinogen Studies Collaboration are listed at the end of this article.

One of the most prominent features of the human brain is the fabulous size of the cerebral cortex and its intricate folding. Cortical folding takes place during embryonic development and is important to optimize the functional organization and wiring of the brain, as well as to allow fitting a large cortex in a limited cranial volume. Pathological alterations in size or folding of the human cortex lead to severe intellectual disability and intractable epilepsy. Hence, cortical expansion and folding are viewed as key processes in mammalian brain development and evolution, ultimately leading to increased intellectual performance and, eventually, to the emergence of human cognition. Here, we provide an overview and discuss some of the most significant advances in our understanding of cortical expansion and folding over the last decades. These include discoveries in multiple and diverse disciplines, from cellular and molecular mechanisms regulating cortical development and neurogenesis, genetic mechanisms defining the patterns of cortical folds, the biomechanics of cortical growth and buckling, lessons from human disease, and how genetic evolution steered cortical size and folding during mammalian evolution.

The outer subventricular zone (OSVZ) is a germinal layer playing key roles in the development of the neocortex, with particular relevance in gyrencephalic species such as human and ferret, where it contains abundant basal radial glia cells (bRGCs) that promote cortical expansion. Here we identify a brief period in ferret embryonic development when apical RGCs generate a burst of bRGCs that become founders of the OSVZ. After this period, bRGCs in the OSVZ proliferate and self-renew exclusively locally, thereby forming a self-sustained lineage independent from the other germinal layers. The time window for the brief period of OSVZ bRGC production is delineated by the coincident downregulation of Cdh1 and Trnp1, and their upregulation reduces bRGC production and prevents OSVZ seeding. This mechanism in cortical development may have key relevance in brain evolution and disease.

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SUMMARYPlants detect changes in day length to induce seasonal patterns of flowering. The photoperiodic pathway accelerates the flowering of Arabidopsis thaliana under long days (LDs) whereas it is inactive under short days (SDs), resulting in delayed flowering. This delay is overcome by exposure of plants to high temperature (27°C) under SDs (27°C-SD). Previously, the high-temperature flowering response was proposed to involve either the impaired activity of MADS-box transcription factor (TF) floral repressors or PHYTO-CHROME-INTERACTING FACTOR 4 (PIF4) TF-mediated activation of FLOWERING LOCUS T (FT), which encodes the output signal of the photoperiodic pathway. We integrate these observations by studying several PIFs, the MADS-box SHORT VEGETATIVE PHASE (SVP) and the photoperiodic pathway under 27°C-SD. We find that the mRNAs of FT and its paralogue TWIN SISTER OF FT (TSF) are increased at dusk under 27°C-SD compared with 21°C-SD, and that this requires PIF4 and PIF5 as well as CONSTANS (CO), a TF that promotes flowering under LDs. The CO and PIF4 proteins are present at dusk under 27°C-SD, and they physically interact. Although Col-0 plants flower at similar times under 27°C-SD and 21°C-LD the expression level of FT is approximately 10-fold higher under 21°C-LD, suggesting that responsiveness to FT is also increased under 27°C-SD, perhaps as a result of the reduced activity of SVP in the meristem. Accordingly, only svp-41 ft-10 tsf-1 plants flowered at the same time under 21°C-SD and 27°C-SD. Thus, we propose that under non-inductive SDs, elevated temperatures increase the activity and sensitize the response to the photoperiod pathway.

The effect of thyroid hormone treatment on hepatic microsomal functions related to NADPH-dependent electron transfer reactions was studied in rats given 0.1 mg T3/kg BW for 1, 2, 3, and 7 consecutive days. This treatment resulted in increased rates of O2-. generation by microsomal fractions, concomitantly with an enhancement in NADPH oxidase activity and decreased cytochrome P-450 content, in livers exhibiting increased respiration. Subsequent studies showed elevated levels of malondialdehyde in microsomal fractions and liver homogenates, as well as augmented chemiluminescent response in the latter system. These results indicate that the calorigenic effect of T3 on the liver tissue is accompanied by a stimulation of microsomal functions involving univalent reduction of oxygen. This cellular response might lead to a greater lipid peroxidative rate and cytochrome P-450 loss as secondary events of thyroid hormone action.