Molaetherium heissigi n. gen., n. sp., an unusual mammal from the Early Oligocene of Germany (Mammalia: Palaeanodonta)

A new genus and species of epoicotheriid,Molaetherium heissigi, is described from the Early Oligocene of Grafenmühle 22, near Pappenheim, Bavaria. It is a tiny, highly fossorial form, closely related to the North American genusEpoicotherium. Asia is considered the center of origin of the suborder Palaeanodonta; from there it dispersed to North America and Europe.     

The epithelial basal lamina of the isolated colonic mucosa: scanning and transmission electron microscopy

The morphology of the rat colonic basement membrane was studied under control conditions and after induction of secretion by distension in the Ussing chamber. The basement membrane was visualized by removing the epithelium with the aid of Ca2+ chelation combined with vibration. Specimens with and without metallic coating were studied with SEM and TEM, respectively. The surface of the basement membrane in the surface region of the epithelium, i.e. between the mouths of the crypts, is rough. In contrast, the deeper parts of the crypts have a rather smooth basal lamina, which is finely pleated. Fenestrations of the basal lamina with a diameter of 0.5-1 microns were found frequently at the surface region, but less frequently in the crypts. Fenestrations with diameters larger than 2 microns were never observed. After the distension experiments and long-time incubation in vitro (5 h), the size of the fenestrations remained unchanged, however, their number increased compared to the controls.     

Detection of genetic variation with radioactive ligands. I. Electrophoretic screening of plasma proteins with a selected panel of compounds.

To detect new genetic variation in human plasma proteins, a panel of 63 radioactive substances were screened as potential radioligands using polyacrylamide gel electrophoresis (PAGE) and autoradiography. Vitamins, hormones, drugs, amino acids, purines, pyrimidines, sugars and lipids labeled with 14C or other radionuclides were among those substances tested. A majority bound to albumin and a smaller fraction to prealbumins and lipoproteins. Several vitamins and hormones bound to specific alpha and beta globulins. (1) Electrophoretic polymorphisms of vitamin D-binding protein (group-specific component), a vitamin B12-binding protein (transcobalamin II), and thyroxine-binding alpha-globulin are described elsewhere. (2) Testosterone-binding beta-globulin (TeBG) showed an electrophoretic polymorphism in Caucasians and a possible deficiency allele. (3) Transcortin showed an electrophoretic doublet in all persons tested but no electrophoretic variation. (4) A protein binding derivative of norepinephrine or epinephrine was identified as transferrin. (5) A nonpolymorphic protein running cathodal to albumin and binding a derivative of riboflavin was tentatively identified as a fraction of albumin with mobility altered as a result of interaction with the ligand.     

Disentangling genetic and epigenetic determinants of ultrafast adaptation

A major rationale for the advocacy of epigenetically mediated adaptive responses is that they facilitate faster adaptation to environmental challenges. This motivated us to develop a theoretical–experimental framework for disclosing the presence of such adaptation‐speeding mechanisms in an experimental evolution setting circumventing the need for pursuing costly mutation–accumulation experiments. To this end, we exposed clonal populations of budding yeast to a whole range of stressors. By growth phenotyping, we found that almost complete adaptation to arsenic emerged after a few mitotic cell divisions without involving any phenotypic plasticity. Causative mutations were identified by deep sequencing of the arsenic‐adapted populations and reconstructed for validation. Mutation effects on growth phenotypes, and the associated mutational target sizes were quantified and embedded in data‐driven individual‐based evolutionary population models. We found that the experimentally observed homogeneity of adaptation speed and heterogeneity of molecular solutions could only be accounted for if the mutation rate had been near estimates of the basal mutation rate. The ultrafast adaptation could be fully explained by extensive positive pleiotropy such that all beneficial mutations dramatically enhanced multiple fitness components in concert. As our approach can be exploited across a range of model organisms exposed to a variety of environmental challenges, it may be used for determining the importance of epigenetic adaptation‐speeding mechanisms in general.     

The synaptic vesicle protein 2C mediates the uptake of botulinum neurotoxin A into phrenic nerves

Botulinum neurotoxins (BoNTs) inhibit neurotransmitter release by selectively cleaving core components of the vesicular fusion machinery. The synaptic vesicle proteins Synaptotagmin-I and -II act as receptors for BoNT/B and BoNT/G. Here we show that BoNT/A also interacts with a synaptic vesicle protein, the synaptic vesicle glycoprotein 2C (SV2C), but not with the homologous proteins SV2A and SV2B. Binding of BoNT/A occurs at the membrane juxtaposed region preceding transmembrane domain 8. A peptide comprising the intravesicular domain between transmembrane domains 7 and 8 specifically reduces the neurotoxicity of BoNT/A at phrenic nerve preparations demonstrating the physiological relevance of this interaction.     

First record of an upper deciduous molar in Desmanella (Uropsilinae,Talpidae, Mammalia)

The dP4 of Desmanella engesseri Ziegler, 1985 from a maxillary which includes the P2 and P3 in crypt, the P4 in eruption and fully erupted dP4 and M1, is described from Petersbuch 28 (Germany; Lower Miocene, MN3/4). The maxillary was studied using X-ray microtomography to make detailed images of the internal and external features of the sample. This is the first record of a dP4 from Desmanella Engesser, 1972. Its shape is unique for fossil talpids, possessing the apomorphic feature of replacing the protocone with a large lingual cingulum. The functional use of deciduous teeth and the process that led to the complete loss of milk teeth in extant talpids are discussed.     

A novel harmony search-K means hybrid algorithm for clustering gene expression data

Recent progress in bioinformatics research has led to the accumulation of huge quantities of biological data at various data sources. The DNA microarray technology makes it possible to simultaneously analyze large number of genes across different samples. Clustering of microarray data can reveal the hidden gene expression patterns from large quantities of expression data that in turn offers tremendous possibilities in functional genomics, comparative genomics, disease diagnosis and drug development. The k- ¬means clustering algorithm is widely used for many practical applications. But the original k-¬means algorithm has several drawbacks. It is computationally expensive and generates locally optimal solutions based on the random choice of the initial centroids. Several methods have been proposed in the literature for improving the performance of the k-¬means algorithm. A meta-heuristic optimization algorithm named harmony search helps find out near-global optimal solutions by searching the entire solution space. Low clustering accuracy of the existing algorithms limits their use in many crucial applications of life sciences. In this paper we propose a novel Harmony Search-K means Hybrid (HSKH) algorithm for clustering the gene expression data. Experimental results show that the proposed algorithm produces clusters with better accuracy in comparison with the existing algorithms.