Purification and unique properties of mammary epithelial stem cells

Elucidation of the cellular and molecular mechanisms that maintain mammary epithelial tissue integrity is of broad interest and paramount to the design of more effective treatments for breast cancer. Evidence from both in vitro and in vivo experiments suggests that mammary cell differentiation is a hierarchical process originating in an uncommitted stem cell with self-renewal potential. However, analysis of the properties and regulation of mammary stem cells has been limited by a lack of methods for their prospective isolation. Here we report the use of multi-parameter cell sorting and limiting dilution transplant analysis to demonstrate the purification of a rare subset of adult mouse mammary cells that are able individually to regenerate an entire mammary gland within 6 weeks in vivo while simultaneously executing up to ten symmetrical self-renewal divisions. These mammary stem cells are phenotypically distinct from and give rise to mammary epithelial progenitor cells that produce adherent colonies in vitro. The mammary stem cells are also a rapidly cycling population in the normal adult and have molecular features indicative of a basal position in the mammary epithelium.     

Molecular mechanism for distinct neurological phenotypes conveyed by allelic truncating mutations

The molecular mechanisms by which different mutations in the same gene can result in distinct disease phenotypes remain largely unknown. Truncating mutations of SOX10 cause either a complex neurocristopathy designated PCWH or a more restricted phenotype known as Waardenburg-Shah syndrome (WS4; OMIM 277580). Here we report that although all nonsense and frameshift mutations that cause premature termination of translation generate truncated SOX10 proteins with potent dominant-negative activity, the more severe disease phenotype, PCWH, is realized only when the mutant mRNAs escape the nonsense-mediated decay (NMD) pathway. We observe similar results for truncating mutations of MPZ that convey distinct myelinopathies. Our experiments show that triggering NMD and escaping NMD may cause distinct neurological phenotypes.     

The plant response： stress in the daily environment

Like animals, plants have evolved to survive in almost every climatic and environmental niche available. They have, however, evolved more sophisticated and varied methods to enable them to survive environmental changes in light, temperature, atmosphere composition, water and nutrients and     

Programmed cell death features in apple suspension cells under low oxygen culture

Suspension-cultured apple fruit cells (Malus pumila Mill. cv. Braeburn) were exposed to a low oxygen atmosphere to test whether programmed cell death (PCD) has a role in cell dysfunction and death under hypoxic conditions. Protoplasts were prepared at various times after low oxygen conditions were established, and viability tested by triple staining with fluorescein diacetate (FDA), propidium iodide (PI) and Hoechst33342 (HO342). DNA breakdown and phosphatidylserine exposure on the plasma membrane were observed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and annexin V binding. About 30% of protoplasts from cells after 48 h under low oxygen showed an increased accumulation of HO342, indicating increased membrane permeability. Positive TUNEL and annexin V results were also only obtained with protoplasts from cells under low oxygen. The results suggest that apple celi death under low oxygen is at least partially PCD mediated, and may explain tissue breakdown under controlled atmosphere (low oxygen) conditions in apple fruit.     

Large fluctuations in speed on Greenland's Jakobshavn Isbrae glacier

It is important to understand recent changes in the velocity of Greenland glaciers because the mass balance of the Greenland Ice Sheet is partly determined by the flow rates of these outlets. Jakobshavn Isbrae is Greenland's largest outlet glacier, draining about 6.5 per cent of the ice-sheet area, and it has been surveyed repeatedly since 1991 (ref. 2). Here we use remote sensing data to measure the velocity of Jakobshavn Isbrae between 1992 and 2003. We detect large variability of the velocity over time, including a slowing down from 6,700 m yr(-1) in 1985 to 5,700 m yr(-1) in 1992, and a subsequent speeding up to 9,400 m yr(-1) by 2000 and 12,600 m yr(-1) in 2003. These changes are consistent with earlier evidence for thickening of the glacier in the early 1990s and rapid thinning thereafter. Our observations indicate that fast-flowing glaciers can significantly alter ice discharge at sub-decadal timescales, with at least a potential to respond rapidly to a changing climate.     

Competition and mutualism among the gut helminths of a mammalian host

Most animal species are infected with multiple parasite species; however, the role of interspecific parasite interactions in influencing parasite dynamics and shaping parasite communities has been unclear. Although laboratory studies have found evidence of cross-immunity, immunosuppression and competition, analyses of hosts in the field have generally concluded that parasite communities are little more than random assemblages. Here we present evidence of consistent interspecific interactions in a natural mammalian system, revealed through the analysis of parasite intensity data collected from a free-ranging rabbit (Oryctolagus cuniculus) population, sampled monthly for a period of 23 yr. The wild rabbit plays host to a diverse gut helminth community that reflects the communities seen in other economically important domestic herbivores. These findings suggest that parasite interactions could have profound implications for the dynamics of parasite communities. The efficacy of parasite control programmes could be jeopardized if such interactions are not taken into account. In contrast, a clear understanding of such interactions may provide the basis for the development of more environmentally acceptable methods of parasite control.