Corridors of migrating neurons in the human brain and their decline during infancy

The subventricular zone of many adult non-human mammals generates large numbers of new neurons destined for the olfactory bulb. Along the walls of the lateral ventricles, immature neuronal progeny migrate in tangentially oriented chains that coalesce into a rostral migratory stream (RMS) connecting the subventricular zone to the olfactory bulb. The adult human subventricular zone, in contrast, contains a hypocellular gap layer separating the ependymal lining from a periventricular ribbon of astrocytes. Some of these subventricular zone astrocytes can function as neural stem cells in vitro, but their function in vivo remains controversial. An initial report found few subventricular zone proliferating cells and rare migrating immature neurons in the RMS of adult humans. In contrast, a subsequent study indicated robust proliferation and migration in the human subventricular zone and RMS. Here we find that the infant human subventricular zone and RMS contain an extensive corridor of migrating immature neurons before 18 months of age but, contrary to previous reports, this germinal activity subsides in older children and is nearly extinct by adulthood. Surprisingly, during this limited window of neurogenesis, not all new neurons in the human subventricular zone are destined for the olfactory bulb--we describe a major migratory pathway that targets the prefrontal cortex in humans. Together, these findings reveal robust streams of tangentially migrating immature neurons in human early postnatal subventricular zone and cortex. These pathways represent potential targets of neurological injuries affecting neonates.     

Neutrophil elastase targets virulence factors of enterobacteria

Shigellae cause bacillary dysentery, a bloody form of diarrhoea that affects almost 200 million people and causes nearly 2 million deaths per year. Shigella invades the colonic mucosa, where it initiates an acute inflammation, rich in neutrophils, that initially contributes to tissue damage and eventually resolves the infection. Neutrophils are phagocytic cells that kill microorganisms but it is unclear how neutrophils control pathogenic bacteria expressing virulence factors that manipulate host cells. In contrast to other cells, neutrophils prevent the escape of Shigella from phagocytic vacuoles in which the bacteria are killed. Here we identify human neutrophil elastase (NE) as a key host defence protein: NE degrades Shigella virulence factors at a 1,000-fold lower concentration than that needed to degrade other bacterial proteins. In neutrophils in which NE is inactivated pharmacologically or genetically, Shigella escapes from phagosomes, increasing bacterial survival. NE also preferentially cleaves virulence factors of Salmonella and Yersinia. These findings establish NE as the first neutrophil factor that targets bacterial virulence proteins.     

Breeding and parental care in the endangered Tehuantepec jackrabbit ( Lepus flavigularis )

We documented date and duration of each breeding phase, breeding rate, nursing behavior, parental care, and leveret survival of the Tehuantepec jackrabbit ( Lepus flavigularis ), a critically endangered lagomorph. Between June 2006 and May 2008, we observed 60 adult radio-collared jackrabbits in Oaxaca, México. Tehuantepec jackrabbits exhibit breeding behaviors 250 days out of the year, with a high-intensity period during the rainy season (May–October). Females give birth to 2 leverets 32 days after copulation. Directly after birth, leverets are put into “beds” or “nests,” which are depressions in the ground covered by prairie grass ( Jouvea pilosa ). Females return to nurse and groom the leverets once per day until the leverets are weaned (12 days after birth). The breeding season and parental care behaviors of Tehuantepec jackrabbits are similar to those of other jackrabbits. Females produced an average of 2 litters per breeding season. The breeding rate for the Tehuantepec jackrabbit (4 leverets per breeding female per breeding season) is lower than the average of other species in the genus Lepus. The survival rate of Tehuantepec jackrabbit leverets (50% at day 19) is higher than that of other leporids. Predation by domestic dogs ( Canis familiaris ) is the main cause of mortality. Understanding reproductive behavior is critical for captive breeding, reintro duction, and conservation efforts for endangered leporids such as the Tehuantepec jackrabbit. Documentamos la fecha y la duración de cada fase de la reproducción, la tasa reproductiva, el amamantamiento, el cuidado parental y los instintos de supervivencia de los lebratos de la liebre de Tehuantepec ( Lepus flavigularis ), un lagomorfo en peligro crítico de extinción. Entre junio de 2006 y mayo de 2008 observamos 60 liebres adultas con collares radiotransmisores en Oaxaca, Mexico. Las liebres de Tehuantepec se reproducen 250 días del año, con un período de alta intensidad durante la estación lluviosa (de mayo a octubre). Las hembras paren 2 lebratos 32 días después de la cópula; colocan a los lebratos en “camas”, o huecos en el suelo cubiertos del pasto Jouvea pilosa, justo después de nacer. Las hembras regresan para amamantar y limpiar a los lebratos una vez cada tarde hasta destetarlos 12 días después de nacer. La temporada de reproducción y el cuidado parental de la liebre de Tehuantepec son parecidos a los de otras liebres. En promedio, las hembras producen 2 crías cada temporada de reproducción. La tasa de reproducción de la liebre de Tehuantepec (4 lebratos por hembra reproductora por temporada de reproducción) está por debajo del promedio de otras especies del género Lepus. La tasa de supervivencia de los lebratos de la liebre de Tehuantepec (50% al día 19) es superior a la que se ha documentado para otros lepóridos, siendo la principal causa de mortalidad la depredación por los perros domésticos ( Canis familiaris ). Es crucial entender el comportamiento reproductor para la crianza en cautiverio, la reintroducción y para los esfuerzos de conservación de lepóridos que están en peligro de extinción tal como occure con la liebre de Tehuantepec.     

Chromosome stability, in the absence of apoptosis, is critical for suppression of tumorigenesis in Trp53 mutant mice

The p53 protein integrates multiple upstream signals and functions as a tumor suppressor by activating distinct downstream genes. At the cellular level, p53 induces apoptosis, cell cycle arrest and senescence. A rare mutant form of p53 with the amino acid substitution R175P, found in human tumors, is completely defective in initiating apoptosis but still induces cell cycle arrest. To decipher the functional importance of these pathways in spontaneous tumorigenesis, we used homologous recombination to generate mice with mutant p53-R172P (the mouse equivalent of R175P in humans). Mice inheriting two copies of this mutation (Trp53(515C/515C)) escape the early onset of thymic lymphomas that characterize Trp53-null mice. At 7 months of age, 90% of Trp53-null mice had died, but 85% of Trp53(515C/515C) mice were alive and tumor-free, indicating that p53-dependent apoptosis was not required for suppression of early onset of spontaneous tumors. The lymphomas and sarcomas that eventually developed in Trp53(515C/515C) mice retained a diploid chromosome number, in sharp contrast to aneuploidy observed in tumors and cells from Trp53-null mice. The ability of mutant p53-R172P to induce a partial cell cycle arrest and retain chromosome stability are crucial for suppression of early onset tumorigenesis.     

Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration

The subventricular zone (SVZ) is a principal source of adult neural stem cells in the rodent brain, generating thousands of olfactory bulb neurons every day. If the adult human brain contains a comparable germinal region, this could have considerable implications for future neuroregenerative therapy. Stem cells have been isolated from the human brain, but the identity, organization and function of adult neural stem cells in the human SVZ are unknown. Here we describe a ribbon of SVZ astrocytes lining the lateral ventricles of the adult human brain that proliferate in vivo and behave as multipotent progenitor cells in vitro. This astrocytic ribbon has not been observed in other vertebrates studied. Unexpectedly, we find no evidence of chains of migrating neuroblasts in the SVZ or in the pathway to the olfactory bulb. Our work identifies SVZ astrocytes as neural stem cells in a niche of unique organization in the adult human brain.     

全致密和非全致密3Y－TZP的高温塑性形变行为

在１２５０～１４５５℃温度下于空气中对全致密和非全致密（相对密度为０．９５）的两种微晶的摩尔分数为０．０３的Ｙ２Ｏ３稳定四方氧化锆多晶体的高温压缩塑性形变行为进行了研究。结果表明，这两种材料形变的主要机理都是通过扩散适应的晶界滑移。非全致密的３Ｙ－ＴＺＰ的流动应力低于全致密的３Ｙ－ＴＺＰ的流动应力，但两种材料的应力指数和蠕变活化能相似。非全致密的３Ｙ－ＴＺＰ在形变过程中发生致密化，且经过１３５０℃以上的温度压缩形变，可以得到全致密的材料。     

Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes

Recent studies have suggested that bone marrow cells possess a broad differentiation potential, being able to form new liver cells, cardiomyocytes and neurons. Several groups have attributed this apparent plasticity to 'transdifferentiation'. Others, however, have suggested that cell fusion could explain these results. Using a simple method based on Cre/lox recombination to detect cell fusion events, we demonstrate that bone-marrow-derived cells (BMDCs) fuse spontaneously with neural progenitors in vitro. Furthermore, bone marrow transplantation demonstrates that BMDCs fuse in vivo with hepatocytes in liver, Purkinje neurons in the brain and cardiac muscle in the heart, resulting in the formation of multinucleated cells. No evidence of transdifferentiation without fusion was observed in these tissues. These observations provide the first in vivo evidence for cell fusion of BMDCs with neurons and cardiomyocytes, raising the possibility that cell fusion may contribute to the development or maintenance of these key cell types.     

Glucose-6-phosphate pools in isolated rat diaphragm

Riassunto é stato studiato l'effetto della concentrazione sul metabolismo del glucosio e del glucosio-6-fosfato nel diaframma isolato di ratto. Si discute brevemente della esistenza di due pools di glucosio-6-fosfato in relazione alle diverse condizioni sperimentali.