STUDIES ON THE FORMATION AND STATE OF DETERMINATION OF THE TRUNK ORGANIZER IN THE NEWT, CYNOPS PYRRHOGASTER

Mesoderm formation in the presumptive trunk organizer was analyzed in gastrulae of Cynops pyrrhogaster. The presumptive trunk organizer showed little or no mesodermal differentiation in the beginning gastrula (0 h embryo). But as soon as the presumptive trunk organizer came into contact with the newly invaginated cranial archenteron roof, it rapidly formed mesoderm. This suggests that this differentiation was brought about by an inductive effect of the underlying cranial archenteron roof. For investigation of this possibility, the presumptive trunk organizer of 0 h embryos (Tr-0) and the newly invaginated cranial archenteron roof (presumptive pharyngeal endoderm and prechordal plate) of successive stages were cultured in isolation and by the sandwich technique. The newly invaginated presumptive pharyngeal endoderm and prechordal plate had no effect on mesoderm formation of the presumptive trunk organizer, and mesodermal differentiation of the combinations was similar to that of the Tr-0 alone. On the other hand, results showed that the prechordal plate, which came into contact with the still uninvaginated presumptive trunk organizer, stimulated dorsalisation of the weakly mesodermized trunk organizer. Based on these results, the stepwise process of mesoderm formation in the trunk organizer is discussed.     

Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer

Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio (_wHR) = 1.09 (95% CI 1.02–1.16), p_trend = 0.017; and n = 3,965, _wHR = 1.04 (95% CI 0.94–1.16), p_trend = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.     

Bioactive factors secreted from mesenchymal stromal cells protect the intestines from experimental colitis in a three-dimensional culture

Background aims

Although mesenchymal stromal cells (MSCs) have shown therapeutic potential in intestinal tissue repair, controversy concerning their short survival and poor biodistribution in recipient tissues still remains. Therefore, we investigated the paracrine role of MSC in three-dimensional culture of colon with experimental colitis.

Calcitonin-derived carrier peptide plays a major role in the membrane localization of a peptide-cargo complex

Bilayers made of dioleoylphosphatidylcholine (DOPC)/dipalmitoylphosphatidylcholine (DPPC) mixture containing or not cholesterol (Chl) were used to investigate the interaction of a carrier peptide with membranes. Atomic force microscopy revealed that the C-terminal 9-32 fragment of human calcitonin (hCT (9-32)), free or coupled to enhanced green fluorescent protein (hCT-eGFP) cargo forms aggregates in the DOPC fluid phase in absence of Chl and in the DPPC enriched liquid-ordered phase when Chl is present. The data show that hCT (9-32) plays a determinant role in the membrane localization of the peptide-cargo complex. They suggest that carpet-like mechanism for membrane destabilization may be involved in the carrier function of hCT (9-32).     

The presence of Compsocerops (Brachyopoidea: Chigutisauridae) (Late Triassic) in southern Brazil with comments on chigutisaurid palaeobiogeography

Abstract: Chigutisauridae is the longest‐lived trematosaurian clade (from early Triassic to early Cretaceous). They were reported in Argentina, Australia, India and South Africa. This contribution reports a putative chigutisaurid specimen in the Carnian of southern Brazil (Santa Maria Formation, Paraná Basin). The material comprises two skull fragments, a mandibular fragment, a clavicular blade and a humerus. Ontogenetic features point to an early development stage of the specimen. The presence of a long, straight and pointed tabular horn, which runs parallel to the skull midline towards its tip, and a distinctive projection in the posterior border of the postparietal indicates a close relationship of the Brazilian chigutisaurid with the Indian Compsocerops cosgriffi. Three distinctive and combined characters suggest that the Brazilian chigutisaurid is a distinctive specimen: the presence of an alar process of the jugal in the ventral margin of the orbit; jugal does not extend well beyond the anterior margin of the orbit; and tabular does not contact the parietal. These characters could justify the erection of a new taxon; however, they might reflect its immature ontogenetic stage as well. Accordingly, we attribute this new specimen to Compsocerops sp. Argentinean and Indian occurrences are dated as Norian, so the presence of a Carnian chigutisaurid in southern Brazil indicates that western Gondwana chigutisaurids have first occupied the Paraná Basin and later migrated towards west (to Argentina) and east (India). However, the presence of ghost chigutisaurid taxa cannot be dismissed, because their long temporal range contrasts with their still short (in comparison with other temnospondyl groups) geographic distribution. Hence, they might have been more geographically widespread than their fossil record suggests.     

Middle–Late Permian tetrapods from the Rio do Rasto Formation,Southern Brazil: a biostratigraphic reassessment

Dias‐da‐Silva, S. 2011: Middle–Late Permian tetrapods from the Rio do Rasto Formation, Southern Brazil: a biostratigraphic reassessment. Lethaia, Vol. 45, pp. 109–120. The Rio do Rasto Formation (Permian of Southern Brazil) was previously regarded as Guadalupian–early Lopingian age. Three tetrapod‐based localities are known: the Serra do Cadeado area, Aceguá and Posto Queimado. The latest tetrapod‐based biostratigraphic contribution considers that the Posto Queimado and Aceguá faunas are coeval and Wordian (middle Guadalupian) in age, correlated to the Isheevo faunas from Eastern Europe and to the Tapinocephalus Assemblage Zone of South Africa; whereas the Serra do Cadeado fauna is Capitanian (late Guadalupian), correlated to the Kotelnich fauna of Eastern Europe and, from bottom to top, to upper Pristerognathus, Tropidostoma and lower Cistecephalus assemblage zones of South Africa. A re‐evaluation of the tetrapods from the Rio do Rasto Formation and new fossil discoveries in the localities of Posto Queimado and Serra do Cadeado area (melosaurine and platyoposaurine temnospondyls, a basal anomodont, a dinocephalian and a basal dicynodont) supports a new tetrapod‐based biostratigraphic scheme for the Rio do Rasto Formation. Accordingly, the age of the fauna at Aceguá is late Roadian‐early Wordian, whereas the locality of Posto Queimado is late Wordian‐Capitanian. The Serra do Cadeado Area is correlated with both southernmost ones (Guadalupian) but also Wuchiapinghian (early Lopingian). □Paraná Basin, Passa Dois Group, tetrapod biostratigraphy, Western Gondwana.     

Leptomonas lactosovorans n. sp., a Lactose-Utilizing Trypanosomatid: Description and Nutritional Requirements1

Leptomonas lactosovorans n. sp. is described from the gut of the reduviid hemipteran Zelurus martinsi. It can be grown in a defined medium. The requirements for amino acids, vitamins, purine, and heme were similar to those established for Crithida fasciculata. Growth is stimulated by aeration. Generation time is longer than for any other insect trypanosomatid described; its utilization of lactose as a carbon source is a unique feature among trypanosomatids.     

Unraveling seasonality in population averages: an examination of seasonal variation in glucose levels in diabetes patients using a large population-based data set

It has been shown that the population average blood glucose level of diabetes patients shows seasonal variation, with higher levels in the winter than summer. However, seasonality in the population averages could be due to a tendency in the individual to seasonal variation, or alternatively due to occasional high winter readings (spiking), with different individuals showing this increase in different winters. A method was developed to rule out spiking as the dominant pattern underlying the seasonal variation in the population averages. Three years of data from three community-serving laboratories in Israel were retrieved. Diabetes patients (N?=?3243) with a blood glucose result every winter and summer over the study period were selected. For each individual, the following were calculated: seasonal average glucose for all winters and summers over the period of study (2006-2009), winter-summer difference for each adjacent winter-summer pair, and average of these five differences, an index of the degree of spikiness in the pattern of the six seasonal levels, and number of times out of five that each winter-summer difference was positive. Seasonal population averages were examined. The distribution of the individual's differences between adjacent seasons (winter minus summer) was examined and compared between subgroups. Seasonal population averages were reexamined in groups divided according to the index of the degree of spikiness in the individual's glucose pattern over the series of seasons. Seasonal population averages showed higher winter than summer levels. The overall median winter-summer difference on the individual level was 8?mg/dL (0.4?mmol/L). In 16.9% (95% confidence interval [CI]: 15.6-18.2%) of the population, all five winter-summer differences were positive versus 3.6% (95% CI: 3.0-4.2%) where all five winter-summer differences were negative. Seasonal variation in the population averages was not attenuated in the group having the lowest spikiness index; comparison of the distributions of the winter-summer differences in the high-, medium-, and low-spikiness groups showed no significant difference (p?=?.213). Therefore, seasonality in the population average blood glucose in diabetes patients is not just the result of occasional high measurements in different individuals in different winters, but presumably reflects a general periodic tendency in individuals for winter glucose levels to be higher than summer levels.