Distinct stem cells contribute to mammary gland development and maintenance

The mammary epithelium is composed of several cell lineages including luminal, alveolar and myoepithelial cells. Transplantation studies have suggested that the mammary epithelium is maintained by the presence of multipotent mammary stem cells. To define the cellular hierarchy of the mammary gland during physiological conditions, we performed genetic lineage-tracing experiments and clonal analysis of the mouse mammary gland during development, adulthood and pregnancy. We found that in postnatal unperturbed mammary gland, both luminal and myoepithelial lineages contain long-lived unipotent stem cells that display extensive renewing capacities, as demonstrated by their ability to clonally expand during morphogenesis and adult life as well as undergo massive expansion during several cycles of pregnancy. The demonstration that the mammary gland contains different types of long-lived stem cells has profound implications for our understanding of mammary gland physiology and will be instrumental in unravelling the cells at the origin of breast cancers.     

Volatile content of lunar volcanic glasses and the presence of water in the Moon's interior

The Moon is generally thought to have formed and evolved through a single or a series of catastrophic heating events, during which most of the highly volatile elements were lost. Hydrogen, being the lightest element, is believed to have been completely lost during this period. Here we make use of considerable advances in secondary ion mass spectrometry to obtain improved limits on the indigenous volatile (CO(2), H(2)O, F, S and Cl) contents of the most primitive basalts in the Moon-the lunar volcanic glasses. Although the pre-eruptive water content of the lunar volcanic glasses cannot be precisely constrained, numerical modelling of diffusive degassing of the very-low-Ti glasses provides a best estimate of 745 p.p.m. water, with a minimum of 260 p.p.m. at the 95 per cent confidence level. Our results indicate that, contrary to prevailing ideas, the bulk Moon might not be entirely depleted in highly volatile elements, including water. Thus, the presence of water must be considered in models constraining the Moon's formation and its thermal and chemical evolution.     

Hydrogen sulphide release to surface waters at the Precambrian/Cambrian boundary

Animal-like multicellular fossils appeared towards the end of the Precambrian, followed by a rapid increase in the abundance and diversity of fossils during the Early Cambrian period, an event also known as the 'Cambrian explosion'. Changes in the environmental conditions at the Precambrian/Cambrian transition (about 542 Myr ago) have been suggested as a possible explanation for this event, but are still a matter of debate. Here we report molybdenum isotope signatures of black shales from two stratigraphically correlated sample sets with a depositional age of around 542 Myr. We find a transient molybdenum isotope signal immediately after the Precambrian/Cambrian transition. Using a box model of the oceanic molybdenum cycle, we find that intense upwelling of hydrogen sulphide-rich deep ocean water best explains the observed Early Cambrian molybdenum isotope signal. Our findings suggest that the Early Cambrian animal radiation may have been triggered by a major change in ocean circulation, terminating a long period during which the Proterozoic ocean was stratified, with sulphidic deep water.     

Experience with moving visual stimuli drives the early development of cortical direction selectivity

The onset of vision occurs when neural circuits in the visual cortex are immature, lacking both the full complement of connections and the response selectivity that defines functional maturity. Direction-selective responses are particularly vulnerable to the effects of early visual deprivation, but it remains unclear how stimulus-driven neural activity guides the emergence of cortical direction selectivity. Here we report observations from a motion training protocol that allowed us to monitor the impact of experience on the development of direction-selective responses in visually naive ferrets. Using intrinsic signal imaging techniques, we found that training with a single axis of motion induced the rapid emergence of direction columns that were confined to cortical regions preferentially activated by the training stimulus. Using two-photon calcium imaging techniques, we found that single neurons in visually naive animals exhibited weak directional biases and lacked the strong local coherence in the spatial organization of direction preference that was evident in mature animals. Training with a moving stimulus, but not with a flashed stimulus, strengthened the direction-selective responses of individual neurons and preferentially reversed the direction biases of neurons that deviated from their neighbours. Both effects contributed to an increase in local coherence. We conclude that early experience with moving visual stimuli drives the rapid emergence of direction-selective responses in the visual cortex.     

The first hominin of Europe

The earliest hominin occupation of Europe is one of the most debated topics in palaeoanthropology. However, the purportedly oldest of the Early Pleistocene sites in Eurasia lack precise age control and contain stone tools rather than human fossil remains. Here we report the discovery of a human mandible associated with an assemblage of Mode 1 lithic tools and faunal remains bearing traces of hominin processing, in stratigraphic level TE9 at the site of the Sima del Elefante, Atapuerca, Spain. Level TE9 has been dated to the Early Pleistocene (approximately 1.2-1.1 Myr), based on a combination of palaeomagnetism, cosmogenic nuclides and biostratigraphy. The Sima del Elefante site thus emerges as the oldest, most accurately dated record of human occupation in Europe, to our knowledge. The study of the human mandible suggests that the first settlement of Western Europe could be related to an early demographic expansion out of Africa. The new evidence, with previous findings in other Atapuerca sites (level TD6 from Gran Dolina), also suggests that a speciation event occurred in this extreme area of the Eurasian continent during the Early Pleistocene, initiating the hominin lineage represented by the TE9 and TD6 hominins.     

Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960

Human immunodeficiency virus type 1 (HIV-1) sequences that pre-date the recognition of AIDS are critical to defining the time of origin and the timescale of virus evolution. A viral sequence from 1959 (ZR59) is the oldest known HIV-1 infection. Other historically documented sequences, important calibration points to convert evolutionary distance into time, are lacking, however; ZR59 is the only one sampled before 1976. Here we report the amplification and characterization of viral sequences from a Bouin's-fixed paraffin-embedded lymph node biopsy specimen obtained in 1960 from an adult female in Léopoldville, Belgian Congo (now Kinshasa, Democratic Republic of the Congo (DRC)), and we use them to conduct the first comparative evolutionary genetic study of early pre-AIDS epidemic HIV-1 group M viruses. Phylogenetic analyses position this viral sequence (DRC60) closest to the ancestral node of subtype A (excluding A2). Relaxed molecular clock analyses incorporating DRC60 and ZR59 date the most recent common ancestor of the M group to near the beginning of the twentieth century. The sizeable genetic distance between DRC60 and ZR59 directly demonstrates that diversification of HIV-1 in west-central Africa occurred long before the recognized AIDS pandemic. The recovery of viral gene sequences from decades-old paraffin-embedded tissues opens the door to a detailed palaeovirological investigation of the evolutionary history of HIV-1 that is not accessible by other methods.     

Activated carbon derived from rice husk by NaOH activation and its application in supercapacitor

Four activated carbon(AC) samples prepared from rice husk under different activation temperatures have been characterized by N2adsorption–desorption isotherms, thermogravimetric analysis(TGA–DTA), Fourier transform infrared spectroscopy(FTIR) and scanning electron microscopy(SEM). The specific surface area of AC sample reached 2681 m2 g 1under activation temperature of 800 1C. The AC samples were then tested as electrode material; the specific capacitance of the as-prepared activated carbon electrode was found to be 172.3 F g 1using cyclic voltammetry at a scan rate of 5 mV s 1and 198.4 F g 1at current density 1000 mA g 1in the charge/discharge mode.& 2014 Chinese Materials Research Society. Production and hosting by Elsevier B.V. All rights reserved.     

The Polycomb group protein EZH2 directly controls DNA methylation

The establishment and maintenance of epigenetic gene silencing is fundamental to cell determination and function. The essential epigenetic systems involved in heritable repression of gene activity are the Polycomb group (PcG) proteins and the DNA methylation systems. Here we show that the corresponding silencing pathways are mechanistically linked. We find that the PcG protein EZH2 (Enhancer of Zeste homolog 2) interacts-within the context of the Polycomb repressive complexes 2 and 3 (PRC2/3)-with DNA methyltransferases (DNMTs) and associates with DNMT activity in vivo. Chromatin immunoprecipitations indicate that binding of DNMTs to several EZH2-repressed genes depends on the presence of EZH2. Furthermore, we show by bisulphite genomic sequencing that EZH2 is required for DNA methylation of EZH2-target promoters. Our results suggest that EZH2 serves as a recruitment platform for DNA methyltransferases, thus highlighting a previously unrecognized direct connection between two key epigenetic repression systems.     

Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection

There is concern that variola virus, the aetiological agent of smallpox, may be used as a biological weapon. For this reason several countries are now stockpiling (vaccinia virus-based) smallpox vaccine. Although the preventive use of smallpox vaccination has been well documented, little is known about its efficacy when used after exposure to the virus. Here we compare the effectiveness of (1) post-exposure smallpox vaccination and (2) antiviral treatment with either cidofovir (also called HPMPC or Vistide) or with a related acyclic nucleoside phosphonate analogue (HPMPO-DAPy) after lethal intratracheal infection of cynomolgus monkeys (Macaca fascicularis) with monkeypox virus (MPXV). MPXV causes a disease similar to human smallpox and this animal model can be used to measure differences in the protective efficacies of classical and new-generation candidate smallpox vaccines. We show that initiation of antiviral treatment 24 h after lethal intratracheal MPXV infection, using either of the antiviral agents and applying various systemic treatment regimens, resulted in significantly reduced mortality and reduced numbers of cutaneous monkeypox lesions. In contrast, when monkeys were vaccinated 24 h after MPXV infection, using a standard human dose of a currently recommended smallpox vaccine (Elstree-RIVM), no significant reduction in mortality was observed. When antiviral therapy was terminated 13 days after infection, all surviving animals had virus-specific serum antibodies and antiviral T lymphocytes. These data show that adequate preparedness for a biological threat involving smallpox should include the possibility of treating exposed individuals with antiviral compounds such as cidofovir or other selective anti-poxvirus drugs.