Systematics and taxonomy of the Spanish Anchitheriinae, and their relationship with regional climate changes: a comment on Eronen et al

In a recent paper, Eronen et al. (2010; hereafter EEFJ) observe differences in occlusal morphology, tooth crown height, and mesowear pattern between populations of the Miocene tridactyl equid Anchitherium from Spain and Germany, proposing that Spanish Anchitherium underwent adaptive evolution to local or regional arid conditions. However, these authors do not take into account the actual diversity of Iberian representatives of Anchitherium, or the fact that the Spanish fossils cover a wider temporal and geographical range than those from Germany. For these reasons, we suggest that their subsequent statistical work should be reconsidered.     

gamma-Butyrobetaine hydroxylation to carnitine in mammalian kidney.

Activity of γ-butyrobetaine hydroxylase (γ-butyrobetaine, 2-oxoglutarate dioxygenase; EC 1.14.11.1) in liver and kidney of several mammalian species was assayed by measurement of tritium release from γ-[2,3-³H]butyrobetaine. Crude extracts from cat, hamster, rabbit, and Rhesus monkey kidneys effectively converted γ-butyrobetaine to carnitine. In these species, the levels of hydroxylating activity in kidney exceeded or nearly equaled the level of γ-butyrobetaine hydroxylase activity in the corresponding liver. In contrast, dog, guinea pig, mouse, and rat kidney exhibited no or insignificant capacity to hydroxylate γ-butyrobetaine. The notion that the liver is the exclusive or primary site of carnitine synthesis must be reconsidered at least for some mammalian species.     

Primate malarias: man and monkeys

The question whether malarias of animals could be considered true zoonoses was examined. The research in this connection for the past decade or so was reviewed. That simian malarias are true zoonoses has been adequately demonstrated. In addition, there is great potential for human malarias being true anthroponoses. The author considers, therefore, that the significance of non-human reservoirs of human malaria in the control or eradication of malaria should be reconsidered.     

Subcellular localization of the spindle proteins Aurora A, Mad2, and BUBR1 assessed by immunohistochemistry.

The spindle checkpoint, the primary mechanism to ensure that two daughter cells receive the same amount of DNA, is compromised in many malignant tumors and has been implicated as a contributor to aneuploidy and carcinogenesis. The extent of expression and subcellular localization of the spindle proteins Aurora A, Mad2, and BUBR1 varies considerably in different immunohistochemical (IHC) reports from archival tumor tissues. Given the conflicting reports in the literature about the localization of these proteins, we examined the subcellular localization of Aurora kinase A, Mad2, and BUBR1 in normal and cancerous human tissues by IHC. In normal tissues, Aurora A was mainly localized to the nucleus when monoclonal or purified polyclonal antibodies were used, and Mad2 was localized to the nucleus, whereas BUBR1 was localized to the cytoplasm. In malignant tissues, Aurora A showed additional staining in the cytoplasm in the majority of tumors analyzed. Furthermore, BUBR1 was also localized to both the nucleus and cytoplasm in a significant fraction of tumors. Subcellular localization of Mad2 was similar in normal and malignant tissues. Thus, the validity of some earlier IHC studies of Aurora A, Mad2, and BUBR1 should be reconsidered, indicating that high-quality antibodies and a high-alkaline antigen-retrieval technique are required to achieve optimal results. We conclude that the subcellular localizations of these spindle proteins are different, although they have overlapping biological functions, and that Aurora A and BUBR1 undergo a shift in the subcellular localization during malignant transformation.     

A fruit and leaves of Rhamnaceous affinities from the late Cretaceous (Maastrichtian) of Colombia

Although Rhamnaceae are distributed worldwide today, the former hypothesis for its Laurasian origins may need to be reconsidered in view of recently discovered fossils from the Guaduas Formation of central Colombia (～68 Ma), including fossil leaves (Berhamniphyllum) and a fruit (Archaeopaliurus boyacensis). Recent phylogenetic studies calibrate the stem of Rhamnaceae at 64 Ma and divide the family into three groups, rhamnoid, ampeloziziphoid, and ziziphoid. Although the fruit, Archaeopaliurus boyacensis, resembles that of Paliurus and suggests a relationship to the Paliureae in the ziziphoid group, associated leaves of Berhamniphyllum conform in architecture to those found today only in the Rhamneae tribe. The Maastrichtian age of these fossils predates the ages previously estimated for the Rhamneae tribe (28.5 Ma) and the Paliureae tribe (31.6 Ma) using a modified clock approach. Based on the new megafossil evidence, two alternative ideas are proposed: (1) that these fossils predate the extant tribes or (2) that the family diversified into modern tribes earlier than previously proposed.     

Mitochondrial and extramitochondrial Ca2+ pools in the perfused rat liver. Mitochondria are not the origin of calcium mobilized by vasopressin

A nondisruptive technique developed by Bellomo et al. (Bellomo, G., Jewell, S. A., Thor, H., and Orrenius, S. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 6842-6846) has been used to examine the distribution of calcium ions between mitochondrial and extramitochondrial compartments in the perfused rat liver. The amount of calcium released by the uncoupler 2,4-dinitrophenol from the mitochondrial compartment was 19 +/- 2 nmol X g-1, wet weight, which is equivalent to a total calcium concentration of 3.5 X 10(-4) M in the mitochondria and is by several orders of magnitude smaller than the concentration thought to be present in these organelles. The amount of calcium released from the liver in the presence of the divalent cation ionophore A 23187 was 96 +/- 7 nmol X g-1, wet weight, which is of the same order of magnitude as the amount released by the calcium-dependent hormone vasopressin (97 +/- 11 nmol X g-1, wet weight). Experiments with different sequential combinations of hormone with uncoupler or ionophore reveal that in the perfused liver, in contrast to isolated hepatocytes or isolated mitochondria, the amount of calcium attributable to the mitochondria is too small to account for the calcium released during hormonal stimulation. Consequently extramitochondrial calcium stores are the main source of cellular calcium mobilized under this condition. In addition these findings imply that in the liver several mitochondrial enzymes, e.g. alpha-oxoglutarate dehydrogenase, can be effectively regulated by calcium and that the role of mitochondria in buffering the cytosolic free calcium in vivo has to be reconsidered.     

Severe infantile encephalomyopathy caused by a mutation in COX6B1, a nucleus-encoded subunit of cytochrome c oxidase

Cytochrome c oxidase (COX) deficiency, one of the most common respiratory-chain defects in humans, has been associated with mutations in either mitochondrial DNA genes or nucleus-encoded proteins that are not part in but promote the biogenesis of COX. Mutations of nucleus-encoded structural subunits were sought for but never found in COX-defective patients, leading to the conjecture that they may be incompatible with extra-uterine survival. We report a disease-associated mutation in one such subunit, COX6B1. Nuclear-encoded COX genes should be reconsidered and included in the diagnostic mutational screening of human disorders related to COX deficiency.     

GPR30 does not mediate estrogenic responses in reproductive organs in mice

The G protein-coupled receptor Gpr30 (Gper) was recently claimed to bind to estradiol and to activate cytoplasmic signal transduction pathways in response to estradiol. However, there are conflicting data regarding the role of Gpr30 as an estrogen receptor (ER): several laboratories were unable to demonstrate estradiol binding to GPR30 or estradiol-activated signal transduction in Gpr30-expressing cells. To clarify the potential role of Gpr30 as an ER, we generated Gpr30-deficient mice. Although Gpr30 was expressed in all reproductive organs, histopathological analysis did not reveal any abnormalities in these organs in Gpr30-deficient mice. Mutant male and female mice were as fertile as their wild-type littermates, indicating normal function of the hypothalamic-pituitary-gonadal axis. Moreover, we analyzed estrogenic responses in two major estradiol target organs, the uterus and the mammary gland. For that purpose, we examined different readout paradigms such as morphological measures, cellular proliferation, and target gene expression. Our data demonstrate that in vivo Gpr30 is dispensable for the mediation of estradiol effects in reproductive organs. These results are in clear contrast to the phenotype of mice lacking the classic ER alpha (Esr1) or aromatase (Cyp19a1). We conclude that the perception of Gpr30 (based on homology related to peptide receptors) as an ER might be premature and has to be reconsidered.     

A study of the auxins in cabbage using countercurrent distribution

The counter-current distribution technique has been applied to the study of the identity of the auxins present in fresh cabbage. The results indicate that the major fraction of the auxin activity is probably due to 3-indoleacetic acid, but this is not established conclusively. In addition to the material presumed to be 3-indoleacetic acid, two other biologically active fractions were obtained from cabbage. Whether these are other auxins or “precursors” of 3-indoleacetic acid has not been established. It has been demonstrated that the colorimetric test which has been used by other workers is not specific for 3-indoleacetic acid, and conclusions which have been based on the use of this test must be reconsidered.     

Ultradian Growth in Prochlorococcus spp

Species of the widespread marine prokaryote Prochlorococcus exhibited ultradian growth (faster than 1 division per day) both in situ and in culture, even though cell division is strictly phased to the light-dark cycle. Under optimal conditions a second DNA replication and cell division closely followed, but did not overlap with, the first division. The timing of cell cycle events was not affected by light intensity or duration, suggesting control by a light-triggered timer or circadian clock rather than by completion of a light-dependent assimilation phase. This mode of ultradian growth has not been observed previously and poses new questions about the regulation of cellular rhythms in prokaryotes. In addition, it implies that conclusions regarding the lack of nutrient limitation of Prochlorococcus in the open ocean, which were based on the appearance that cells were growing at their maximal rate, need to be reconsidered.     

Two-component in situ forming supramolecular hydrogels as advanced biomaterials in vitreous body surgery

Polymeric β-CD and poly{(2-acrylamido-2-methyl-1-propanesulfonic acid sodium salt)-co-[6-(acrylamido)-N-adamantylhexaneamide]} are synthesized to build in situ forming hydrogels based on host/guest interactions, so called physical hydrogels. The use of these hydrogels as a potential vitreous body substitute is discussed and recommended. Potential changes in cell morphology and cell vitality of the retinal ganglion cell line RGC-5 are determined. DSC experiments with artificial membrane structures are performed. The analyses show that β-CD overrides the harmful effects of the highly toxic adamantyl-modified polymer. Although the final hydrogel is considered to be biocompatible, the application as a biomaterial has to be reconsidered.     

E-N-cadherin heterodimers define novel adherens junctions connecting endoderm-derived cells

Intercellular junctions play a pivotal role in tissue development and function and also in tumorigenesis. In epithelial cells, decrease or loss of E-cadherin, the hallmark molecule of adherens junctions (AJs), and increase of N-cadherin are widely thought to promote carcinoma progression and metastasis. In this paper, we show that this "cadherin switch" hypothesis does not hold for diverse endoderm-derived cells and cells of tumors derived from them. We show that the cadherins in a major portion of AJs in these cells can be chemically cross-linked in E-N heterodimers. We also show that cells possessing E-N heterodimer AJs can form semistable hemihomotypic AJs with purely N-cadherin-based AJs of mesenchymally derived cells, including stroma cells. We conclude that these heterodimers are the major AJ constituents of several endoderm-derived tissues and tumors and that the prevailing concept of antagonistic roles of these two cadherins in developmental and tumor biology has to be reconsidered.     

Ultrapure ajulemic acid has improved CB2 selectivity with reduced CB1 activity

Ajulemic acid, a side-chain analog of Δ⁸-THC-11-oic acid, was designed as a potent therapeutic agent free of the psychotropic adverse effects typical of most cannabinoids. Subsequent studies of ajulemic acid have yielded widely divergent findings on the occurrence of these adverse effects. To help resolve these discrepancies, we have prepared highly purified ajulemic acid using a different synthetic method than previously reported in the literature and compared its cannabinoid receptor binding constants with those obtained using several other preparations from different sources. Whereas CB2 binding did not vary greatly among all of the samples, the CB1 binding showed a wide range of affinities. The highly purified product (JBT-101) reported here had the weakest affinity for CB1 while the original preparation (HU-239) showed the strongest affinity for CB1. The CB1/CB2 ratio of affinities was 12.3 for JBT-101 whereas that for HU-239 was 0.19, a 65-fold difference. Functional responses such as catalepsy and hypothermia using JBT-101 versus HU-239 displayed reduced CB1 activity in keeping with the receptor binding data. Thus, earlier conclusions on the limited therapeutic index for ajulemic acid need to be reconsidered in the light of the data now obtained using JBT-101.     

Regulation of CDK4

Cyclin-dependent kinase (CDK)4 is a master integrator that couples mitogenic and antimitogenic extracellular signals with the cell cycle. It is also crucial for many oncogenic transformation processes. In this overview, we address various molecular features of CDK4 activation that are critical but remain poorly known or debated, including the regulation of its association with D-type cyclins, its subcellular location, its activating Thr172-phosphorylation and the roles of Cip/Kip CDK "inhibitors" in these processes. We have recently identified the T-loop phosphorylation of CDK4, but not of CDK6, as a determining target for cell cycle control by extracellular factors, indicating that CDK4-activating kinase(s) might have to be reconsidered.     

Abscisic acid does not disrupt either the Arabidopsis FCA-FY interaction or its rice counterpart in vitro

We examined the effect of (+)-ABA on the in vitro interaction of rice FCA and FY homologs, OsFCA and OsFY. From this analysis, we found no disruption of the OsFCA-OsFY complexes by ABA treatment. This result prompted us to examine the effect of ABA on the FCA-FY interaction. In these experiments, we could not reproduce the inhibitory effect of (+)-ABA on the interaction between FCA and FY. Based on these combined results, we believe that the inhibitory effect of (+)-ABA on the FCA-FY interaction should be cautiously reconsidered.     

Problems in recognizing the self: a neuropsychological approach to the positive symptoms of schizophrenia

This article present a review of recent work on cognitive neuroscience approaches of schizophrenia. Some of the symptoms displayed by schizophrenic patients can be reconsidered within the framework of disorganization of well identified cognitive functions, like self-recognition. Neuroimaging techniques can reveal in these patients disruption of neural networks normally involved in such functions.     

Some New Phenomena in Macronuclear Development of Euplotes patella Exconjugants

Two new phenomena were observed during macronuclear development in E. patella. During the formation of giant chromosomes, the number of chromosomes decreased while individual chromosomes gradually became longer and thicker. Immediately before macronuclear elongation, ring-like anlagen appeared, which did not contain chromatin at their centers. The course of macronuclear development in Euplotes is reconsidered in light of these findings.     

Ultradian Growth in Prochlorococcus spp.

Species of the widespread marine prokaryote Prochlorococcus exhibited ultradian growth (faster than 1 division per day) both in situ and in culture, even though cell division is strictly phased to the light-dark cycle. Under optimal conditions a second DNA replication and cell division closely followed, but did not overlap with, the first division. The timing of cell cycle events was not affected by light intensity or duration, suggesting control by a light-triggered timer or circadian clock rather than by completion of a light-dependent assimilation phase. This mode of ultradian growth has not been observed previously and poses new questions about the regulation of cellular rhythms in prokaryotes. In addition, it implies that conclusions regarding the lack of nutrient limitation of Prochlorococcus in the open ocean, which were based on the appearance that cells were growing at their maximal rate, need to be reconsidered.     

Considérations sur l’extension géographique du Néolithique final à « livre de beurre » en Touraine et Poitou (France)

The “livre de beurre” blades debitage is classically attached to Grand-Pressigny country (Indre-et-Loire). This question is reconsidered by the autors to ligth on their knowledge of the sites and raw materials in a broadest geographic expanse: the South of Touraine and Poitou. Cultural attribution of this practice is also reconsidered and replaced in largest context.     

Studies on the crossability relationships of some spinous Solanums

Summary Cytogenetic studies involving six species of spinous Solanums have been made using the parameters of crossability/fertility relationships and chromosome pairing in parental and derived hybrid genomes. These studies have made it possible to integrate hybrid reproductive performance with observed cytological phenomena and draw inferences on concerned intergenomic homeologies. It has been found that species' differences, as they exist, are ascribable to chromosome repatterning, in their divergence and maintenance as distinct taxa. In the light of these studies, the grouping of these species has to be reconsidered.