FMRI studies have revealed three scene-selective regions in human visual cortex (the Parahippocampal Place Area (PPA), Transverse Occipital Sulcus (TOS) and RetroSplenial Cortex (RSC)), which have been linked to higher-order functions such as navigation, scene perception/recognition, and contextual association. Here, we document corresponding (presumptively homologous) scene-selective regions in the awake macaque monkey, based on direct comparison to human maps, using identical stimuli and largely overlapping fMRI procedures. In humans, our results showed that the three scene-selective regions are centered near - but distinct from - the gyri/sulci for which they were originally named. In addition, all these regions are located within or adjacent to known retinotopic areas. Human RSC and PPA are located adjacent to the peripheral representation of primary and secondary visual cortex, respectively. Human TOS is located immediately anterior/ventral to retinotopic area V3A, within retinotopic regions LO-1, V3B, and/or V7. Mirroring the arrangement of human regions FFA and PPA (which are adjacent to each other in cortex), the presumptive monkey homologue of human PPA is located adjacent to the monkey homologue of human FFA, near the posterior superior temporal sulcus. Monkey TOS includes the region predicted from the human maps (macaque V4d), extending into retinotopically-defined V3A. A possible monkey homologue of human RSC lies in the medial bank, near peripheral V1. Overall, our findings suggest a homologous neural architecture for scene-selective regions in visual cortex of humans and non-human primates, analogous to the face-selective regions demonstrated earlier in these two species.
Our data establish that HOTAIR is an important long noncoding RNA that primarily serves as a prognostic factor for glioma patient survival, as well as a biomarker for identifying glioma molecular subtypes, a critical regulator of cell cycle progression.
The proproliferative transcription factor KLF5 plays an important role in promoting cell proliferation and tumorigenesis. KLF5 is a short-lived protein that can be rapidly degraded through the ubiquitin-proteasome pathway in cancer cells. However, the mechanisms regulating protein stability remain poorly understood. In this study, the tumor suppressor Fbw7, a component of the SCF complex (SCF Fbw7 ) E3 ubiquitin ligase, specifically promoted the degradation and ubiquitination of KLF5 but had little effect on the stability of KLF4. Fbw7 interacted with KLF5 in a CDC4 phosphodegron (CPD)-dependent manner. Three CPDs were found in the KLF5 protein. Simultaneous mutation of these CPDs significantly abolished Fbw7-mediated ubiquitination and degradation. Furthermore, Fbw7 deficiency dramatically delayed KLF5 turnover and led to the accumulation of KLF5 protein in cancer cells. Glycogen synthase kinase-3 could phosphorylate and promote Fbw7-mediated KLF5 degradation. More importantly, Fbw7 negatively regulated the biological activity of KLF5 in gene regulation and cell proliferation. Taken together, these data indicate that Fbw7 is a key negative regulator controlling KLF5-mediated cell proliferation and suggest an additional mechanism linking the loss of Fbw7 function to tumorigenesis. Sp/Krüppel-like factor (KLF) 2 transcription factors are involved in various biological processes and human diseases (1, 2). KLF5 (also known as IKLF and BTEB2) is a basic KLF transcription factor that regulates cell proliferation and plays an important role in diverse physiological and pathological processes, including stemness, inflammation, and atherogenesis (3, 4). As a proproliferative factor, KLF5 also has essential functions in tumorigenesis (3). Increasing evidence indicates that KLF5 can function as an oncogenic protein by promoting cell proliferation in many cancers (5-10). For example, a high expression level of KLF5 correlates with a shorter survival time in breast cancer patients (11). Inhibition of KLF5 expression by pharmacological or genetic methods significantly reduces colorectal cancer cell proliferation (6, 12). However, under certain conditions, KLF5 can also act as a tumor suppressor in some cancers (13,14). The exact mechanisms underlying these apparently contradictory functions are not completely understood.The function of KLF5 is regulated at multiple levels. KLF5 transcription is regulated by several signaling molecules such as Wnt and lysophosphatidic acid (15,16). At the post-translational level, KLF5 function is modulated by phosphorylation, sumoylation, and acetylation (3). Phosphorylation of KLF5 by protein kinase C enhances its transactivation activity and its interaction with CBP (cAMP-responsive element-binding protein-binding protein) (17), whereas sumoylation regulates KLF5-mediated lipid metabolism and its subcellular localization (18,19).KLF5 is an unstable protein with a short half-life in cells. Its protein levels are regulated negatively by the ubiquitin-proteasome pathway (20). The E3 ubiquiti...
Introduction: Surgically implanted chambers with removable grids are routinely used for studying patterns of neuronal activity in primate brains; however, accessing target tissues is significantly constrained by standard grid designs. Typically, grids are configured with a series of guide holes drilled vertically, parallel to the walls of the chamber, thus targeted sites are limited to those in line vertically with one of the guide holes. Methods: By using the three-dimensional modeling software, a novel grid was designed to reach the targeted sites far beyond the standard reach of the chamber. The grid was fabricated using conventional machining techniques and three-dimensional printing. Results: A pilot study involving microinjection of the magnetic resonance (MR) contrast agent gadolinium into the discrete regions of interest (ROIs) in the temporal cortex of an awake, behaving monkey demonstrated the effectiveness of this new design of the guide grid. Using multiple different angles of approach, we were readily able to access 10 injection sites, which were up to 5 mm outside the traditional, orthogonal reach of the chamber.
ABSTRACT:The function of breast cancer resistance protein (BCRP) and its role in drug absorption, distribution, and elimination has recently been evaluated. The objective of the present study was to examine the expression, localization, and functional characteristics of BCRP in Caco
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