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861.
Translation initiation is a critical step in protein synthesis. Previously, two major mechanisms of initiation were considered
as essential: prokaryotic, based on SD interaction; and eukaryotic, requiring cap structure and ribosomal scanning. Although
discovered decades ago, cap-independent translation has recently been acknowledged as a widely spread mechanism in viruses,
which may take place in some cellular mRNA translations. Moreover, it has become evident that translation can be initiated
on the leaderless mRNA in all three domains of life. New findings demonstrate that other distinguishable types of initiation
exist, including SD-independent in Bacteria and Archaea, and various modifications of 5′ end-dependent and internal initiation
mechanisms in Eukarya. Since translation initiation has developed through the loss, acquisition, and modification of functional
elements, all of which have been elevated by competition with viral translation in a large number of organisms of different
complexity, more variation in initiation mechanisms can be anticipated. 相似文献
862.
863.
Khan ZU Martín-Montañez E Baxter MG 《Cellular and molecular life sciences : CMLS》2011,68(10):1737-1754
Visual perception and memory are the most important components of vision processing in the brain. It was thought that the
perceptual aspect of a visual stimulus occurs in visual cortical areas and that this serves as the substrate for the formation
of visual memory in a distinct part of the brain called the medial temporal lobe. However, current evidence indicates that
there is no functional separation of areas. Entire visual cortical pathways and connecting medial temporal lobe are important
for both perception and visual memory. Though some aspects of this view are debated, evidence from both sides will be explored
here. In this review, we will discuss the anatomical and functional architecture of the entire system and the implications
of these structures in visual perception and memory. 相似文献
864.
The maintenance of mucosal barrier equilibrium in the intestine requires a delicate and dynamic balance between enterocyte
loss by apoptosis and the generation of new cells by proliferation from stem cell precursors at the base of the intestinal
crypts. When the balance shifts towards either excessive or insufficient apoptosis, a broad range of gastrointestinal diseases
can manifest. Recent work from a variety of laboratories has provided evidence in support of a role for receptors of the innate
immune system, including Toll-like receptors 2, 4, and 9 as well as the intracellular pathogen recognition receptor NOD2/CARD15,
in the initiation of enterocyte apoptosis. The subsequent induction of enterocyte apoptosis in response to the activation
of these innate immune receptors plays a key role in the development of various intestinal diseases, including necrotizing
enterocolitis, Crohn’s disease, ulcerative colitis, and intestinal cancer. This review will detail the regulatory pathways
that govern enterocyte apoptosis, and will explore the role of the innate immune system in the induction of enterocyte apoptosis
in gastrointestinal disease. 相似文献
865.
Rodríguez-Muñoz M Sánchez-Blázquez P Vicente-Sánchez A Bailón C Martín-Aznar B Garzón J 《Cellular and molecular life sciences : CMLS》2011,68(17):2933-2949
A series of pharmacological and physiological studies have demonstrated the functional cross-regulation between MOR and NMDAR.
These receptors coexist at postsynaptic sites in midbrain periaqueductal grey (PAG) neurons, an area implicated in the analgesic
effects of opioids like morphine. In this study, we found that the MOR-associated histidine triad nucleotide-binding protein
1 (HINT1) is essential for maintaining the connection between the NMDAR and MOR. Morphine-induced analgesic tolerance is prevented
and even rescued by inhibiting PKC or by antagonizing NMDAR. However, in the absence of HINT1, the MOR becomes supersensitive
to morphine before suffering a profound and lasting desensitization that is refractory to PKC inhibition or NMDAR antagonism.
Thus, HINT1 emerges as a key protein that is critical for sustaining NMDAR-mediated regulation of MOR signaling strength.
Thus, HINT1 deficiency may contribute to opioid-intractable pain syndromes by causing long-term MOR desensitization via mechanisms
independent of NMDAR. 相似文献
866.
Fanelli F Mauri M Capra V Raimondi F Guzzi F Ambrosio M Rovati GE Parenti M 《Cellular and molecular life sciences : CMLS》2011,68(18):3109-3120
The structure-based design of a mutant form of the thromboxane A(2) prostanoid receptor (TP) was instrumental in characterizing the structural determinants of the hetero-dimerization process of this G protein coupled receptor (GPCR). The results suggest that the hetero-dimeric complexes between the TPα and β isoforms are characterized by contacts between hydrophobic residues in helix 1 from both monomers. Functional characterization confirms that TPα-TPβ hetero-dimerization serves to regulate TPα function through agonist-induced internalization, with important implications in cardiovascular homeostasis. The integrated approach employed in this study can be adopted to gain structural and functional insights into the dimerization/oligomerization process of all GPCRs for which the structural model of the monomer can be achieved at reasonable atomic resolution. 相似文献
867.
Lopez-Castejón G Baroja-Mazo A Pelegrín P 《Cellular and molecular life sciences : CMLS》2011,68(18):3095-3107
Plasticity is a well-known property of macrophages that is controlled by different changes in environmental signals. Macrophage
polarization is regarded as a spectrum of activation phenotypes adjusted from one activation extreme, the classic (M1), to
the other, the alternative (M2) activation. Here we show, in vitro and in vivo, that both M1 and M2 macrophage phenotypes
are tightly coupled to specific patterns of gene expression. Novel M2-associated markers were characterized and identified
as genes controlling the extracellular metabolism of ATP to generate pyrophosphates (PPi). Stimulation of M1 macrophages with
PPi dampens both NLR and TLR signaling and thus mediates cytokine production. In this context extracellular PPi enhanced the
resolution phase of a murine peritonitis model via a decrease in pro-inflammatory cytokine production. Therefore, our study
reveals an additional level of plasticity modulating the resolution of inflammation. 相似文献
868.
Biological cells harbor a variety of molecular machines that carry out mechanical work at the nanoscale. One of these nanomachines
is the bacterial motor protein SecA which translocates secretory proteins through the protein-conducting membrane channel
SecYEG. SecA converts chemically stored energy in the form of ATP into a mechanical force to drive polypeptide transport through
SecYEG and across the cytoplasmic membrane. In order to accommodate a translocating polypeptide chain and to release transmembrane
segments of membrane proteins into the lipid bilayer, SecYEG needs to open its central channel and the lateral gate. Recent
crystal structures provide a detailed insight into the rearrangements required for channel opening. Here, we review our current
understanding of the mode of operation of the SecA motor protein in concert with the dynamic SecYEG channel. We conclude with
a new model for SecA-mediated protein translocation that unifies previous conflicting data. 相似文献
869.
Yvonne G. J. van Helden Roger W. L. Godschalk Hans J. M. Swarts Peter C. H. Hollman Frederik J. van Schooten Jaap Keijer 《Cellular and molecular life sciences : CMLS》2011,68(3):489-504
Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in lung are largely unknown. We performed microarray
gene expression analysis on lung tissue of BC supplemented beta-carotene 15,15′-monooxygenase 1 knockout (Bcmo1
−/−) mice, which are—like humans—able to accumulate BC. Our main observation was that the genes were regulated in an opposite direction in male and female Bcmo1
−/− mice by BC. The steroid biosynthetic pathway was overrepresented in BC-supplemented male Bcmo1
−/− mice. Testosterone levels were higher after BC supplementation only in Bcmo1
−/− mice, which had, unlike wild-type (Bcmo1
+/+) mice, large variations. We hypothesize that BC possibly affects hormone synthesis or metabolism. Since sex hormones influence
lung cancer risk, these data might contribute to an explanation for the previously found increased lung cancer risk after
BC supplementation (ATBC and CARET studies). Moreover, effects of BC may depend on the presence of frequent human BCMO1 polymorphisms, since these effects were not found in wild-type mice. 相似文献
870.
The skin is our primary shield against microbial pathogens and has evolved innate and adaptive strategies to enhance immunity
in response to injury or microbial insult. The study of antimicrobial peptide (AMP) production in mammalian skin has revealed
several of the elegant strategies that AMPs use to prevent infection. AMPs are inducible by both infection and injury and
protect the host by directly killing pathogens and/or acting as multifunctional effector molecules that trigger cellular responses
to aid in the anti-infective and repair response. Depending on the specific AMP, these molecules can influence cytokine production,
cell migration, cell proliferation, differentiation, angiogenesis and wound healing. Abnormal production of AMPs has been
associated with the pathogenesis of several cutaneous diseases and plays a role in determining a patient’s susceptibility
to pathogens. This review will discuss current research on the regulation and function of AMPs in the skin and in skin disorders. 相似文献