γ-Butyrobetaine hydroxylase catalyses a Stevens type rearrangement

γ-Butyrobetaine hydroxylase (BBOX) is a 2-oxoglutarate and Fe(II)-dependent oxygenase that catalyses the final step of L-carnitine biosynthesis in animals. BBOX catalyses the oxidation of 3-(2,2,2-trimethylhydrazinium)propionate (THP), a clinically used BBOX inhibitor, to form multiple products including 3-amino-4-(methyamino)butanoic acid (AMBA), which is proposed to be formed via a Stevens type rearrangement mechanism. We report the synthesis of AMBA and confirm that it is a product of the BBOX catalysed oxidation of THP. AMBA reacts with formaldehyde, which is produced enzymatically by BBOX, to give a cyclic adduct.     

A-hydroxyphosphonate oligonucleotides: a promising DNA type?

The synthesis of monomers (S)-1, (R)-1 and 2 derived from (5'S)-, (5'R)-2'-deoxythymidine-5'-C-phosphonic acids and 2',5'-dideoxythymidine-5'-C-phosphonic acids was elaborated. The protection of the 5'-hydroxyl by the methoxycarbonyl group was a key step of the synthesis. Prepared monomers were used for the solid-phase assembly of several types oligothymidylate 15-mers (S)-3, (S)-4, (S)-5, (R)-4 and (R)-5 containing the chiral 3'-O-P-CH(OH)-5' internucleotide linkage. Their hybridization properties with dA15 and rA15 were studied as well as their resistance against nuclease cleavage.     

Answering a century old riddle: brachydactyly type Al

In 1903, Farabee analyzed the heredity of the human digital malformation, brachydactyly, the first recorded disorder of the autosomal dominant Mendelian trait. In 1951, Bell classified this type of brachydactyly as type A1 (BDA1). Over 100 cases from different ethnic groups have so far been reported. However, the real breakthrough in identifying the cause of BDA1 has only taken place in the last few years with the progress of the mapping and identification of one of the genes responsible for this disorder, thus providing an answer for a century old riddle. In this article, we attempt to review the current state of knowledge on the genetic features of BDA1 with its century-old history and signalling pathway of IHH, and also discuss genotype-phenotype correlation not only of BDA1, but also of all types of brachydactyly.     

Momordica charantia extract, a herbal remedy for type 2 diabetes, contains a specific 11β-hydroxysteroid dehydrogenase type 1 inhibitor

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the intracellular regeneration of active cortisol from inert cortisone in key metabolic tissues, thus regulating ligand access to glucocorticoid receptors. There is strong evidence that increased adipose 11β-HSD1 activity may be an important aetiological factor in the current obesity and diabetes type 2 epidemics. Hence, inhibition of 11β-HSD1 has emerged as a promising anti-diabetic strategy, a concept that is largely supported by numerous studies in rodent models as well as limited clinical data with prototype inhibitors. Momordica charantia (also known as bitter melon, bitter gourd or karela) is traditionally used for treatment of diabetes in Asia, South America, the Caribbean, and East Africa. In the present study, we show that M. charantia extract capsules contain at least one ingredient with selective 11β-HSD1 inhibitory activity. The finding constitutes an interesting additional explanation for the well-documented anti-diabetic and hypoglycaemic effects of M. charantia.     

Answering a century old riddle： brachydactyly type A1

In 1903, Farabee analyzed the heredity of the human digital malformation, brachydactyly, the first recorded disorder of the autosomal dominant Mendelian trait. In 1951, Bell classified this type of brachydactyly as type A 1 (BDA 1). Over 100 cases from different ethnic groups have so far been reported. However, the real breakthrough in identifying the cause of BDA 1 has only taken place in the last few years with the progress of the mapping and identification of one of the genes responsible for this disorder, thus providing an answer for a century old riddle. In this article, we attempt to review the current state of knowledge on the genetic features of BDA 1 with its century-old history and signalling pathway of IHH, and also discuss genotype-phenotype correlation not only of BDA 1, but also of all types of brachydactyly.     

Pulse waves for a semi-discrete Morris–Lecar type model

 We establish the existence of a pulse traveling wave for an infinite system of ODEs modeling a one dimensional string of nerve cells of identical Morris–Lecar type dynamics:

Alteration of 11β-hydroxysteroid dehydrogenase type 1 in skeletal muscle in a rat model of type 2 diabetes

Recent investigations have demonstrated that activation of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in liver and adipose tissue is closely related to the pathogenesis of obesity and diabetes. However, the relationship between alteration of 11β-HSD1 and the pathogenesis of type 2 diabetes in skeletal muscle is still unclear. A rat model of Type 2 diabetes was developed by high fat diet feeding combined with multiple low dose streptozotocin injection (30 mg/kg, i.p. twice). Intraperitoneal glucose tolerance test, insulin tolerance test were performed. Fasting blood glucose, fasting insulin, total cholesterol, triglyceride were measured. The protein and mRNA level of 11β-HSD1 and glucocorticoid receptor in gastrocnemius muscle were determined. The alteration of insulin signaling pathway related protein was investigated. We found that the protein levels of 11β-HSD1 and glucocorticoid receptor were significantly increased (P < 0.05); the mRNA level of 11β-HSD1 was also elevated (P < 0.05); the mRNA level of glucocorticoid receptor was decreased (P < 0.05). After insulin stimulation, diabetic rats had no significant changes in the level of the insulin receptor β-subunit (IR-β), AKT, as in phosphorylated AKT in the gastrocnemius muscle compared to its basal state. Similar results were observed in the protein expression level of glucose transporter 4 (GLUT4). Our data indicate that the alteration of 11β-HSD1 at protein and mRNA level may be related to the abnormality of insulin signal pathway in skeletal muscle, this effect may be mediated by glucocorticoid receptor.     

Genetic and clinical mosaicism in a patient with neurofibromatosis type 1

Patients with typical features of neurofibromatosis type 1 (NF1) limited to a specific body segment are usually referred to as having segmental NF1, which is generally assumed to be the result of somatic mosaicism for a NF1 mutation. Mosaicism has also been demonstrated at the molecular level in some sporadic cases with phenotypically classic NF1. In the present report, we describe a patient with NF1 disease manifestations throughout the whole body, but leaving a few sharply delineated segments of the skin unaffected, suggestive of revertant mosaicism. A large intragenic deletion was found by mutation analysis using long-range RT-PCR. The intra-exonic breakpoints were characterized in exon 13 and exon 28, resulting in a deletion of 99,571 bp at the genomic level. The presence of two genetically distinct cell populations, confirming mosaicism for this NF1 mutation, was shown by analysis of several tissues. Revertant mosaicism was excluded by demonstrating heterozygosity for markers residing in the deletion region. The findings in this patient demonstrate two things: (1) although the entire body is affected, mosaicism can still be suspected at clinical examination and proven by DNA analysis and skin biopsies; (2) long-range RT-PCR is a feasible method for demonstrating large intragenic deletions in NF1.     

Phenylphenalenone phytoalexins, will they be a new type of fungicide?

Phenylphenalenones represent a kind of phytoalexins produced in leaves and rhyzomes of banana and plantains (Musaceae), as well as in species of other families. These compounds are synthesized in plants by induction with aminoglycosides, or in the first stages of attack by the pathogenic fungus Mycosphaerella fijensis, a causal agent of the disease known as Black Sigatoka, which reduces banana production. In this paper we report the biosynthesis, synthesis and antifungal activities of these kinds of compounds and discus the possibility to use phytoalexins inductors as plant protectants.     

Cutting edge: is vasoactive intestinal peptide a type 2 cytokine?

A component of the chemical language shared by the immune and nervous system is the expression of neuropeptides by immune cells. Vasoactive intestinal peptide (VIP) was shown to be produced by T lymphocytes. Here we investigate whether T cell subsets differentially express VIP. Our studies indicate that, upon specific Ag stimulation, Th2 and T2 cells, but not Th1 and T1 cells derived from TCR transgenic (Tg) mice, express VIP mRNA and protein, and secrete VIP. Following immunization with the specific Ag, significant levels of VIP are present in the serum of syngeneic, non-Tg hosts that receive Th2, but not Th1 Tg cells. Th2 Tg cells recovered from the non-Tg hosts immunized with the specific Ag, but not with an irrelevant Ag, express intracellular VIP. Because VIP is produced by Ag-stimulated type 2 T cells, and differentially affects Th1 and Th2 cells, could VIP be viewed as a type 2 cytokine?     

Does a type specimen necessarily or contingently belong to its species?

In a recent article, Alex Levine raises a paradox. It appears that, given some relatively uncontroversial premises about how a species term comes to refer to its species, a type specimen belongs necessarily and contingently to its species. According to Levine, this problem arises if species are individuals rather than natural kinds. I argue that the problem can be generalized: the problem also arises if species are kinds and type specimens are paradigmatic members used to baptize names for species. Indeed, the same problem arises with respect to kinds like gold and the samples used to ground names for them. After arguing that the paradox arises whether or not species are individuals, I attempt to show how the paradox can be resolved. Levine's argument that a type specimen belongs necessarily to its species is specious. The appeal of the argument stems from a failure to distinguish between two different modal statements concerning type specimens, one de dicto and the other de re. Type specimens belong contingently to their respective species. Even so, they can be known a priori to belong to them: hence, that a particular type specimen belongs to its species is an example of contingent a priori knowledge.     

Cytogenetic mapping of a novel locus for type II Waardenburg syndrome

An Italian family in which Waardenburg syndrome type II (WS2) segregates together with a der(8) chromosome from a (4p;8p) balanced translocation was studied. Cytogenetic analysis by painting and subtelomeric probe hybridization positioned the chromosome 8 breakpoint at p22-pter. Fluorescence in situ hybridization analysis with yeast artificial chromosomes from a contig spanning the 8p21-pter region refined the breakpoint in an interval of less than 170 kb between markers WI-3823 and D8S1819. The only cloned gene for WS2 is that for microphtalmia (MITF) on chromosome 3p. In this family, MITF mutations were excluded by sequencing the whole coding region. The 8p23 region may represent a third locus for WS2 (WS2C).     

Is adrenomedullin a causal agent in some cases of type 2 diabetes?

The study of two populations with a recent onset of type 2 diabetes showed that a subset of the patients had higher levels of adrenomedullin (AM) than the rest of the diabetics. In this subset, physiological elevations of AM might have triggered the disease in predisposed individuals. Diabetics showed higher levels of AM than healthy controls. In addition, glycemia was measured in diabetic rats after injection of saline, AM, or antiAM antibody. AM elevated glycemia, whereas the antibody reduced circulating glucose to normal. These results suggest that manipulation of AM levels could represent a new approach in the management of diabetes for the appropriate individuals.     

Do Plasmodium ookinetes invade a specific cell type in the mosquito midgut?

Recent debate in Plasmodium ookinete invasion has been centered on whether the parasite chooses a specific cell type to cross the midgut epithelium in the mosquito. A few publications have described the mosquito midgut being composed of complex surface-structures, histochemically and biochemically diverse cell types, and have proposed that Plasmodium gallinaceum ookinetes prefers a specific cell type (Ross cell) in Aedes aegypti for crossing the midgut epithelium. Two recent publications reported, however, that with differential interference contrast microscopy, all midgut epithelial cells in uninfected mosquitoes appear structurally similar and argued that ookinetes do not invade a specific cell type. These observations are discussed here in the context of the 'Ross cell' hypothesis.     

Astrovirus as a possible cause of congenital tremor type AII in piglets?

Background

Congenital tremor is associated with demyelination of the brain and spinal cord and is clinically noted as outbreaks of trembling and shaking in newborn piglets during a limited time-period. Six forms of the disease have been described, where form AII may be caused by an, as yet, unidentified viral infection. This study aimed to investigate the presence of astrovirus and circovirus by sequencing and polymerase chain reaction (PCR) analysis and by relating the findings to the occurrence of disease and lesions in the brain, in 4–6 days-old piglets obtained from a clinical outbreak of congenital tremor.

Results

In piglets with congenital tremor, there were mild to moderate vacuolar changes of the white matter in the cerebrum, brain stem and cerebellum. In healthy piglets, less conspicuous vacuolar changes were detected. One healthy and one diseased piglet were positive for porcine circovirus type 2. The nested pan-PCR showed the presence of astrovirus in at least one brain region in all piglets and by sequencing, two different porcine astrovirus lineages were identified.

Conclusions

The results do not support previous studies identifying porcine circovirus type 2 as the cause of congenital tremor. The demonstration of astrovirus in the brain of piglets suffering from congenital tremor is interesting. However, astrovirus was demonstrated in both healthy and diseased individuals and therefore, further studies are warranted to determine the possible involvement of astrovirus in the pathogenesis of congenital tremor in pigs.

     

Global analysis of a stoichiometric producer–grazer model with Holling type functional responses

Cells, the basic units of organisms, consist of multiple essential elements such as carbon, nitrogen, and phosphorus. The scarcity of any of these elements can strongly restrict cellular and organismal growth. During recent years, ecological models incorporating multiple elements have been rapidly developed in many studies, which form a new research field of mathematical and theoretical biology. Among these models, the one proposed by Loladze et al. (Bull Math Biol 62:1137–1162, 2000) is prominent and has been highly cited. However, the global analysis of this nonsmooth model has never been done. The aim of this paper is to provide the complete global analysis for the model with Holling type I functional response and perform a bifurcation analysis for the model with Holling type II functional response.     

Isolation and partial purification of a novel type II restriction endonuclease Bsu121 I,from Bacillus subtilis – Bsu121I,a type II restriction endonuclease from Bacillus subtilis

A new type II restriction endonuclease which we designated as Bsu121I has been isolated from gram-positive bacterium Bacillus subtilis strain 121 and partially purified. The restriction endonuclease was isolated from cell extracts using step-wise purification through ammonium sulfate precipitation, followed by phosphocellulose column chromatography. SDS-PAGE profile showed denatured molecular weights (23 and 67 kDa) of the endonuclease. The partially purified enzyme restricted pBR322 DNA into two fragments of 3200 and 1700 bp. The endonuclease activity required Mg⁺² as cofactor like other type II endonucleases.