Cellular reprogramming allows for the
The sequestosome 1/p62 protein has been implicated in the regulation of a multitude of cellular processes such as NF-кB signaling, NRF2-driven oxidative stress response, protein turnover through the ubiquitin-proteasome pathway and the autophagosome/lysosome pathway, apoptosis and cellular metabolism. The domain structure of p62 also reflects this functional complexity since the protein appears to be a mosaic of protein interaction domains and motifs. Deregulation of the level and function of p62 and/or p62 mutations have been linked to a number of human diseases including Paget’s disease of the bone, obesity, liver diseases, tumorigenesis and neurodegenerative diseases such as amyotrophic lateral sclerosis and Alzheimer’s disease. In this article, we review the current understanding of the involvement of p62 in cellular processes under physiologic and pathological conditions.
The recent identification of cardiac progenitor cells (CPCs) provides a new paradigm for studying and treating heart disease. To realize the full potential of CPCs for therapeutic purposes, it is essential to understand the genetic and epigenetic mechanisms guiding CPC differentiation into cardiomyocytes, smooth muscle, or endothelial cells. ATP-dependent chromatin remodelers mediate one critical epigenetic mechanism. These large multiprotein complexes open up chromatin to modulate transcription factor access to DNA. SWI/SNF, one of the major types of chromatin remodelers, plays a key role in various aspects of development (
Glycogen synthase kinase 3β (GSK3β) is a multifunctional serine/threonine kinase. It is particularly abundant in the developing central nervous system (CNS). Since GSK3β has diverse substrates ranging from metabolic/signaling proteins and structural proteins to transcription factors, it is involved in many developmental events in the immature brain, such as neurogenesis, neuronal migration, differentiation and survival. The activity of GSK3β is developmentally regulated and is affected by various environmental/cellular insults, such as deprivation of nutrients/trophic factors, oxidative stress and endoplasmic reticulum stress. Abnormalities in GSK3β activity may disrupt CNS development. Therefore, GSK3β is a critical signaling protein that regulates brain development. It may also determine neuronal susceptibility to damages caused by various environmental insults.
Influenza is an important public health issue, especially with the aging of the population, since the most serious consequences of the illness affect the elderly. Between 1979 and 2001, approximately 41000 annual deaths have been attributed to influenza in the United States (
Respiratory syncytial virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants and is the most frequent cause of lower respiratory tract infections in children. Efficacious vaccination has been a longstanding goal in neonates. Due to immaturity of the neonatal immune system, vaccination has shown limited success in stimulating the neonatal endogenous immune system. Advances in the understanding of neonatal immunology have resulted in renewed development of neonatal vaccination. In this article, we review recent advances in neonatal anti-RSV vaccination strategies, including active and passive vaccination approaches, with emphasis on the effect of maternal neutralizing antibody and the role of maternal antibody in neonatal immune modulations. Recent reports in a variety of antiviral vaccine animal models have shown that maternal antibody, different from conventional vaccination, plays an immune modulatory role in the newborn immune system. Active immunization of the pregnant mother and the offspring can effectively stimulate and maintain potent neonatal immune responses, including an endogenous cytotoxic response and neutralizing antibody generation. The induced newborn endogenous antiviral immunity can last up to 6 months, and effectively blunt viral replication. Immune complexes, formed from the integral binding of the maternal neutralizing antibody and viral vaccine antigen, may play an important role in the maternal antibody-mediated neonatal immune response. The underlying mechanisms and future perspectives are discussed.
At least six major genotypes of Hepatitis C virus (HCV) cause liver diseases worldwide. The efficacy rates with current standard of care are about 50% against genotype 1, the most prevalent strain in the United States, Europe and Japan. Therefore more effective pan-genotypic therapies are needed. HCV RNA replication provides a number of validated targets for virus-specific and potentially pan-genotypic inhibitors.
Aerobic metabolism is fundamental for almost all animal life. Cellular consumption of oxygen (O2) and production of carbon dioxide (CO2) signal metabolic states and physiologic stresses. These respiratory gases are also detected as environmental cues that can signal external food quality and the presence of prey, predators and mates. In both contexts, animal nervous systems are endowed with mechanisms for sensing O2/CO2 to trigger appropriate behaviors and maintain homeostasis of internal O2/CO2. Although different animal species show different behavioral responses to O2/CO2, some underlying molecular mechanisms and pathways that function in the detection of respiratory gases are fundamentally similar and evolutionarily conserved. Studies of
Crystals of calcium oxalate have been observed among members from most taxonomic groups of photosynthetic organisms ranging from the smallest algae to the largest trees. The biological roles for calcium oxalate crystal formation in plant growth and development include high-capacity calcium regulation, protection against herbivory, and tolerance to heavy metals. Using a variety of experimental approaches researchers have begun to unravel the complex mechanisms controlling formation of this biomineral. Given the important roles for calcium oxalate formation in plant survival and the antinutrient and pathological impact on human health through its presence in plant foods, researchers are avidly seeking a more comprehensive understanding of how these crystals form. Such an understanding will be useful in efforts to design strategies aimed at improving the nutritional quality and production of plant foods.
Mitogen-activated protein kinases ERK1 and ERK2 have been implicated in various pathophysiological events of the CNS, but their specific roles in cell processes under physiologic and pathological conditions remain to be determined. ERK1/2 was originally identified as a kinase activity that mediates neuronal survival and neuroprotection, but it was subsequently found that ERK1/2 also plays a critical role in neurodegeneration. This dichotomy makes it difficult to target ERK1/2 for neuroprotection. Accumulating evidence suggests that ERK1 and ERK2 may play distinct functions in a variety of cell fate decisions. In this review, I summarize recent evidence for distinct roles for individual ERK isoforms in pathophysiology of the CNS.