No abstract

Defects in the endosomal-lysosomal pathway have been implicated in a number of neurodegenerative disorders. A key step in the endocytic regulation of transmembrane proteins occurs in a subset of late-endosomal compartments known as multivesicular bodies (MVBs), whose formation is controlled by endosomal sorting complex required for transport (ESCRT). The roles of ESCRT in dendritic maintenance and neurodegeneration remain unknown. Here, we show that mSnf7-2, a key component of ESCRT-III, is highly expressed in most mammalian neurons. Loss of mSnf7-2 in mature cortical neurons caused retraction of dendrites and neuronal cell loss. mSnf7-2 binds to CHMP2B, another ESCRT-III subunit, in which a rare dominant mutation is associated with frontotemporal dementia linked to chromosome 3 (FTD3). Ectopic expression of the mutant protein CHMP2B(Intron5) also caused dendritic retraction prior to neurodegeneration. CHMP2B(Intron5) was associated more avidly than CHMP2B(WT) with mSnf7-2, resulting in sequestration of mSnf7-2 in ubiquitin-positive late-endosomal vesicles in cortical neurons. Moreover, loss of mSnf7-2 or CHMP2B(Intron5) expression caused the accumulation of autophagosomes in cortical neurons and flies. These findings indicate that ESCRT-III dysfunction is associated with the autophagy pathway, suggesting a novel neurodegeneration mechanism that may have important implications for understanding FTD and other age-dependent neurodegenerative diseases.

MicroRNAs (miRNAs) have been implicated in regulating various aspects of animal development, but their functions in neurogenesis are largely unknown. Here we report that loss of miR-9a function in the Drosophila peripheral nervous system leads to ectopic production of sensory organ precursors (SOPs), whereas overexpression of miR-9a results in a severe loss of SOPs. We further demonstrate a strong genetic interaction between miR-9a and senseless (sens) in controlling the formation of SOPs in the adult wing imaginal disc. Moreover, miR-9a suppresses Sens expression through its 3 untranslated region. miR-9a is expressed in epithelial cells, including those adjacent to SOPs within proneural clusters, suggesting that miR-9a normally inhibits neuronal fate in non-SOP cells by down-regulating Sens expression. These results indicate that miR-9a ensures the generation of the precise number of neuronal precursor cells during development.[Keywords: MicroRNA; SOP; Senseless; Drosophila; PNS] Supplemental material is available at http://www.genesdev.org.

Summary Human pluripotent stem cells offer promise for use in cell-based therapies for brain injury and diseases. However, their cellular behavior is poorly understood. Here we show that the expression of the brain-specific microRNA-9 (miR-9) is turned on in human neural progenitor cells (hNPCs) derived from human embryonic stem cells. Loss of miR-9 suppressed proliferation but promoted migration of hNPCs cultured in vitro. hNPCs without miR-9 activity also showed enhanced migration when transplanted into mouse embryonic brains or adult brains of a mouse model of stroke. These effects were not due to precocious differentiation of hNPCs. One of the key targets directly regulated by miR-9 encodes stathmin, which increases microtubule instability and whose expression in hNPCs correlates inversely with that of miR-9. Partial inhibition of stathmin activity suppressed the effects of miR-9 loss on proliferation and migration of human or embryonic rat neural progenitors. These results identify miR-9 as a novel regulator that coordinates the proliferation and migration of hNPCs.

The most massive globular cluster in the Milky Way, ω Centauri, is thought to be the remaining core of a disrupted dwarf galaxy 1, 2 , as expected within the model of hierarchical merging 3, 4 . It contains several stellar populations having different heavy elemental abundances supplied by supernovae 5 -a process known as metal enrichment. Although M22 appears to be similar to ω Cen 6 , other peculiar globular clusters do not 7,8 . Therefore ω Cen and M22 are viewed as exceptional, and the presence of chemical inhomogeneities in other clusters is seen as 'pollution' from the intermediate-mass asymptotic-giant-branch stars expected in normal globular clusters 9 . Here we report Ca abundances for seven globular clusters and compare them to ω Cen. Calcium and other heavy elements can only be supplied through numerous supernovae explosions of massive stars in these stellar systems 10 , but the gravitational potentials of the present-day clusters cannot preserve most of the ejecta from such explosions 11 . We conclude that these globular clusters, like ω Cen, are most probably the relics of more massive primeval dwarf galaxies that merged and disrupted to form the proto-Galaxy.The Sejong/ARCSEC Ca uvby survey program was initiated in 2006 to investigate the homogenous metallicity scale for globular clusters and to obtain the complete metallicity distribution function of the Galactic bulge using the hk index [12 . The Ca filter in the hk index measures ionized calcium H and K lines, which have been frequently used to calibrate metallicity scale for globular clusters 13,14 . The utility of the hk index is that it is known to be about three times more sensitive to metallicity than the m 1 index is for stars more metal-poor than the Sun and it has half the sensitivity of the m 1 index to interstellar reddening 12 . During the last three years, we have used more than 85 nights of CTIO 1.0-m telescope time for this project. The telescope was equipped with an STA 4k × 4k CCD camera, providing a plate scale of 0.289 arcsec/pixel and a field of view of 20 × 20 arcmin. All of our targets accompanied with standards were observed under the photometric weather conditions and most of targets were repeatedly visited between separate runs. The photometry of our targets and standards were analyzed using DAOPHOT II, ALLSTAR, and ALLFRAME 15,16 .In the course of metallicity calibration of red giant branch (RGB) stars in GCs, we found that many GCs show split in the RGB in their hk versus V color-magnitude diagrams (Figs 1 and 2). The prime examples are M22 and NGC1851. In particular, the double RGB sequence in M22 is very intriguing. The differential reddening effect and the contamination from the off cluster 1 populations cannot explain the double RGB sequences in M22 (see Supplementary Information). It has been debated for decades whether this cluster is chemically inhomogeneous or not, but the recent high resolution spectroscopic study of 17 RGB stars in the cluster suggests that it contains chemically inhomogeneous subpopulations 6...

Autophagy, an evolutionarily conserved cellular degradation pathway of the lysosome, is associated with many physiological and pathological processes. The hallmark of autophagy is the formation of the autophagosome that engulfs and degrades cytosolic components via its fusion with the lysosome, in either a selective or a non-selective manner. Autophagy is tightly regulated by proteins encoded by autophagy-related (atg) genes. Among these proteins, ATG8/LC3 is essential for autophagosome biogenesis/maturation and it also functions as an adaptor protein for selective autophagy. In mammalian cells, several homologs of yeast Atg8 such as MAP1LC3, GABARAP, and GABARAPL 1/2 have been identified. However, the biological relevance of this gene diversity in higher eukaryotes, and their specific roles, are largely unknown. In this review, we describe the mammalian ATG8/LC3 family and discuss recent advancements in understanding their roles in the autophagic process. [BMB Reports 2016; 49(8): 424-430]

A single, multidrug-resistant strain was responsible for increased incidence of this serotype before introduction of the pneumococcal 7-valent conjugate vaccine.

Among the 53 serotypes of human adenoviruses (HAdVs), identified to date, only a limited number have been associated with human respiratory infections. The epidemiology of each of the serotypes differs depending on the location and/or time of surveillance. This study was performed to elucidate the epidemiology of HAdV respiratory infections by comprehensive serotyping of the HAdVs isolated from the respiratory tract of Korean children. HAdVs isolated from respiratory specimens of Korean children over 17 consecutive years (1991-2007) were typed by the neutralization test or molecular methods, including two-sets of multiplex PCR assays, and/or sequence analysis of the hexon gene. From January 1991 through December 2007, a total of 741 isolates were obtained from nasal aspirates of children hospitalized or requiring medical treatment in the emergency room. All isolates were type-determined successfully and 13 different serotypes were identified, which included HAdV serotypes 1-8, 11, 19, 34, 37, and 41. HAdV-3 (n = 285, 37.7%) and HAdV-7 (n = 181, 23.9%) were the predominant serotypes; HAdV-8, -11, -19, -34, -37, and -41 were not usually associated with respiratory diseases. HAdV-3 was present both during outbreaks and in sporadic cases. HAdV-7 emerged in a very large outbreak, followed by smaller outbreaks. HAdV-1, -2, -4, -5, and -6 were isolated sporadically throughout the study period. In conclusion, a total of 13 different serotypes of HAdV were detected among Korean children with respiratory tract infections. HAdV-3 and HAdV-7 were the most common serotypes, and they were associated with HAdV outbreaks.