Identification of cardiac stem cells within mature cardiac myocytes

Cardiac stem cells are described in a number of mammalian species including humans. Cardiac stem cell clusters consisting of both lineage-negative and partially committed cells are generally identified between contracting cardiac myocytes. In the present study, c-kit⁺, Sca⁺, and Isl1⁺ stem cells were revealed to be located inside the sarcoplasm of cardiac myocytes in myocardial cell cultures derived from newborn, 20-, and 40-day-old rats. Intracellularly localized cardiac stem cells had a coating or capsule with a few pores that opened into the host cell sarcoplasm. The similar structures were also identified in the suspension of freshly isolated myocardial cells (ex vivo) of 20- and 40-day-old rats. The results from this study provide direct evidence for the replicative division of encapsulated stem cells, followed by their partial cardiomyogenic differentiation. The latter is substantiated by the release of multiple transient amplifying cells following the capsule rupture. In conclusion, functional cardiac stem cells can reside not only exterior to but also within cardiomyocytes.     

Probing disorders of the nervous system using reprogramming approaches

The groundbreaking technologies of induced pluripotency and lineage conversion have generated a genuine opportunity to address fundamental aspects of the diseases that affect the nervous system. These approaches have granted us unrestricted access to the brain and spinal cord of patients and have allowed for the study of disease in the context of human cells, expressing physiological levels of proteins and under each patient's unique genetic constellation. Along with this unprecedented opportunity have come significant challenges, particularly in relation to patient variability, experimental design and data interpretation. Nevertheless, significant progress has been achieved over the past few years both in our ability to create the various neural subtypes that comprise the nervous system and in our efforts to develop cellular models of disease that recapitulate clinical findings identified in patients. In this Review, we present tables listing the various human neural cell types that can be generated and the neurological disease modeling studies that have been reported, describe the current state of the field, highlight important breakthroughs and discuss the next steps and future challenges.     

Systematics of Pseudorchis albida s.l. (Orchidaceae) in Europe and North America

In Scandinavia Pseudorchis albida (Orchidaceae)usually divided into the lowland and subalpine P. albida s.s. and the more or less alpine P. straminea. There have been some uncertainties and conflicting views concerning die taxonomic treatment of diese taxa. To address this issue, herbarium specimens of P. albida s.l. were studied for variation in morphological characters. A small-scale population study approach was used, as herbarium sheets with two or three plants were used as population samples. Canonical Variates Analysis (CVA) indicated a distinction between taxa in population means, corresponding to P. albida s.s. and P. straminea , respectively. Principal Components Analysis (PCA), however, revealed an overlap between individuals of the two taxa. The PGA analysis, furthermore, revealed that the overlap was considerably larger in material from Central Europe man in material from Fennoscandia. Student t -tests on separate characters confirmed the picture, wim more characters significantly different in Fennoscandian than in Central European material. Furthermore, a Tukey-Kramer test revealed that there were small differences between regional populations of P. albida s.s. , while there were several significant differences in single characters between the Norm American regional population of P. straminea , as compared with the Central European and Fennoscandian regional populations. In Central Europe there is no clear separation between taxa, while in Fennoscandia the taxa are more clearly separated. This probably means that there is a difference in the time of establishment in the different regions. The author suggests a distinction of taxa at the subspecies level, and argues that the clear distinction seen in Fennoscandian material is due to separate immigration histories for die two subspecies into Fennoscandia after the last period of glaciation.     

Phosphorylation of elF-4E and initiation of protein synthesis in P19 embryonal carcinoma cells

Mitogenic stimulation of protein synthesis is accompanied by an increase in elF-4E phosphorylation. The effect on protein synthesis by induction of differentiation is less well known. We treated P19 embryonal carcinoma cells with the differentiating agent retinoic acid and found that protein synthesis increased during the first hour of addition. However, the phosphorylation state, as well as the turnover of phosphate on elF-4E, remained unchanged. Apparently, the change in protein synthesis after RA addition is regulated by another mechanism than elF-4E phosphorylation. By using P19 cells overexpressing the EGF receptor, we show that the signal transduction pathway that leads to phosphorylation of elF-4E is present in P19 cells; the EGF-induced change in phosphorylation of elF-4E in these cells is likely to be regulated by a change in elF-4E phosphatase activity. These results suggest that the onset of retinoic acid-induced differentiation is triggered by a signal transduction pathway which involves changes in protein synthesis, but not elF-4E phosphorylation. © 1995 Wiley-Liss, Inc.     

Divergence in germination traits among arctic and alpine populations of <Emphasis Type="Italic">Koenigia islandica</Emphasis>: light requirements

Light is known to regulate conservative germination strategies and the formation of seed banks. Although these strategies are crucial to survival in tundra environments—especially for annuals—light requirements for germination in arctic–alpine species are seldom investigated. Furthermore, environmental differences between arctic and alpine regions are expected to lead to evolutionary divergence among conspecific populations in seed germination strategies. In this study, we report important differences in germination light requirements among six arctic and alpine populations of the annual Koenigia islandica. Light had little effect on germination of the seeds from Iqaluit (Nunavut, Canada), Yukon (Canada), and Jasper (Alberta, Canada), whereas the seeds from the most severe climates, Svalbard (Norway) and Colorado (USA), had strong light requirements. Stratification of the seeds had little influence on their germination light requirements, with the exception of the population from Dovre (Norway), in which it induced a strong light requirement. Possible adaptive explanations and some implications of these observed germination patterns are discussed.     

Normal human adipose tissue functions and differentiation in patients with biallelic LPIN1 inactivating mutations

Lipin-1 is a Mg²⁺-dependent phosphatidic acid phosphatase (PAP) that in mice is necessary for normal glycerolipid biosynthesis, controlling adipocyte metabolism, and adipogenic differentiation. Mice carrying inactivating mutations in the Lpin1 gene display the characteristic features of human familial lipodystrophy. Very little is known about the roles of lipin-1 in human adipocyte physiology. Apparently, fat distribution and weight is normal in humans carrying LPIN1 inactivating mutations, but a detailed analysis of adipose tissue appearance and functions in these patients has not been available so far. In this study, we performed a systematic histopathological, biochemical, and gene expression analysis of adipose tissue biopsies from human patients harboring LPIN1 biallelic inactivating mutations and affected by recurrent episodes of severe rhabdomyolysis. We also explored the adipogenic differentiation potential of human mesenchymal cell populations derived from lipin-1 defective patients. White adipose tissue from human LPIN1 mutant patients displayed a dramatic decrease in lipin-1 protein levels and PAP activity, with a concomitant moderate reduction of adipocyte size. Nevertheless, the adipose tissue develops without obvious histological signs of lipodystrophy and with normal qualitative composition of storage lipids. The increased expression of key adipogenic determinants such as SREBP1, PPARG, and PGC1A shows that specific compensatory phenomena can be activated in vivo in human adipocytes with deficiency of functional lipin-1.