Yield depression in methanol-utilizing batch cultures

Summary Yield depression, as opposed to growth inhibition, in batch cultures of methanol-utilizing microorganisms is discussed. Under conditions where the yield coefficient varies, the effect on oxygen demand has been predicted for exponentionally growing cultures.     

Effects of weak electromagnetic fields on global electrocortical activity

Effects of weak electromagnetic fields are considered on recently proposed covariant and generalized coupling models of global electrocortical activity. A method to calculate the ratio of components of signal velocities is given. First-order shift in frequencies is obtained in the presence of a weak, time-varying magnetic field.     

Activation of an adrenergic pro-drug through sequential stereoselective action of tandem target enzymes.

The synthetic amino acid, 3,4-dihydroxyphenylserine (DOPS) has been of great interest for many years as an adrenergic pro-drug, since the L-threo diastereomer of DOPS can be a precursor of R-(-)-norepinephrine, the natural form of this neurotransmitter. We now report bioactivation of DOPS to the potent pharmacological agent, noradrenalone (arterenone), via sequential stereoselective action by two target enzymes--dopamine beta-monooxygenase (DBM) and L-aromatic amino acid decarboxylase (AADC)--acting in tandem. Enzymatic activation is stereospecific, with only the L-erythro DOPS diastereomer producing noradrenalone; this is consistent with the known stereospecificities of AADC and DBM. These results provide a heretofore unrecognized rationale for the bioactivity of L-erythro DOPS and provide a basis for the design of new adrenergic pro-drugs.     

Influence of Various Factors on Toxicity of Culture Filtrate of a Drechslera maydis Strain from Costus speciosus

Drechslera maydis causing severe leaf blight of Costus speciosus, produced toxic matabolites in vitro. Maximum toxin was produced in modified Fries’ medium if its carbon source was substituted with glucose and nitrogen source with asparagine. Highest toxin accumulation was found at 21 days of incubation and with the initial pH 5.0. The toxin was stable in acidic condition (pH 3.5—7.0) but unstable under alkaline conditions.     

In vitro propagation of a multipurpose leguminous tree (Pterocarpus marsupium Roxb.) using nodal explants

Pterocarpus marsupium (Bijasal) is a valuable multipurpose forest tree. The regeneration rate in natural habitat is low and the tree is overexploited. An in vitro propagation protocol has been developed from nodal explants obtained from in vitro raised 18-day-old axenic seedlings. The highest shoot regeneration frequency (85%), maximum number of multiple shoots (8.6) as well as length (4.8 cm) were induced from nodal explants on Murashige and Skoog (MS) medium amended with 4.0 μM 6-benzyladenine (BA), 0.5 μM indole-3-acetic acid (IAA) and 20 μM adenine sulphate (AdS). The percentage of shoot multiplication as well as the number of shoots per node remained the same during the first two subculture, afterwards a decline was recorded. Rooting was best induced in microshoots excised from proliferated shoot cultures on semisolid hormone-free half-strength MS medium, after a pulse (dip) treatment for 7 days in half-strength MS liquid medium containing 100 μM indole-3-butyric acid (IBA) and 15.84 μM phloroglucinol (PG). The in vitro-raised plantlets were potted and acclimatized under culture room conditions for 4 weeks before their transfer to a greenhouse, where the established plants showed 75% survival.     

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia

There are several lines of evidence supporting the role of de novo mutations as a mechanism for common disorders, such as autism and schizophrenia. First, the de novo mutation rate in humans is relatively high, so new mutations are generated at a high frequency in the population. However, de novo mutations have not been reported in most common diseases. Mutations in genes leading to severe diseases where there is a strong negative selection against the phenotype, such as lethality in embryonic stages or reduced reproductive fitness, will not be transmitted to multiple family members, and therefore will not be detected by linkage gene mapping or association studies. The observation of very high concordance in monozygotic twins and very low concordance in dizygotic twins also strongly supports the hypothesis that a significant fraction of cases may result from new mutations. Such is the case for diseases such as autism and schizophrenia. Second, despite reduced reproductive fitness¹ and extremely variable environmental factors, the incidence of some diseases is maintained worldwide at a relatively high and constant rate. This is the case for autism and schizophrenia, with an incidence of approximately 1% worldwide. Mutational load can be thought of as a balance between selection for or against a deleterious mutation and its production by de novo mutation. Lower rates of reproduction constitute a negative selection factor that should reduce the number of mutant alleles in the population, ultimately leading to decreased disease prevalence. These selective pressures tend to be of different intensity in different environments. Nonetheless, these severe mental disorders have been maintained at a constant relatively high prevalence in the worldwide population across a wide range of cultures and countries despite a strong negative selection against them². This is not what one would predict in diseases with reduced reproductive fitness, unless there was a high new mutation rate. Finally, the effects of paternal age: there is a significantly increased risk of the disease with increasing paternal age, which could result from the age related increase in paternal de novo mutations. This is the case for autism and schizophrenia³. The male-to-female ratio of mutation rate is estimated at about 4–6:1, presumably due to a higher number of germ-cell divisions with age in males. Therefore, one would predict that de novo mutations would more frequently come from males, particularly older males⁴. A high rate of new mutations may in part explain why genetic studies have so far failed to identify many genes predisposing to complexes diseases genes, such as autism and schizophrenia, and why diseases have been identified for a mere 3% of genes in the human genome. Identification for de novo mutations as a cause of a disease requires a targeted molecular approach, which includes studying parents and affected subjects. The process for determining if the genetic basis of a disease may result in part from de novo mutations and the molecular approach to establish this link will be illustrated, using autism and schizophrenia as examples.     

Reduction of nucleic acid content in cell biomass of methanol-utilizing mixed bacterial culture by heat treatment

Summary A heat treatment method to reduce nucleic acid content in cell biomass of a mixed methanol-utilizing bacterial culture was studied. Maximum nucleic acid reduction in the bacterial cells was achieved by using heat shock at 65°C for 5–10 min followed by 2 h incubation at 55°C and 7.2±0.2 pH. In this treatment, 81–85% nucleic acid content was removed from the cells without affecting their true protein content and essential amino acids profile.     

Spacetime representation of global electrocortical activity

A model for global electrocortical activity is developed by considering telencephalonic structures as mass of linked oscillators generating activity with a number of resonant modes. Equations for the signals are written in the comoving frame and then transformed into the laboratory frame. The state transition matrix is obtained in the presence of electric and magnetic fields.     

Role of calcineurin biosignaling in cell secretion and the possible regulatory mechanisms

Cyclic adenosine monophosphate (cAMP) and calcium ions (Ca²⁺) are two chemical molecules that play a central role in the stimulus-dependent secretion processes within cells. Ca²⁺ acts as the basal signaling molecule responsible to initiate cell secretion. cAMP primarily acts as an intracellular second messenger in a myriad of cellular processes by activating cAMP-dependent protein kinases through association with such kinases in order to mediate post-translational phosphorylation of those protein targets. Put succinctly, both Ca²⁺ and cAMP act by associating or activating other proteins to ensure successful secretion. Calcineurin is one such protein regulated by Ca²⁺; its action depends on the intracellular levels of Ca²⁺. Being a phosphatase, calcineurin dephosphorylate and other proteins, as is the case with most other phosphatases, such as protein phosphatase 2A (PP2A), PP2C, and protein phosphatase-1 (PP1), will likely be activated by phosphorylation. Via this process, calcineurin is able to affect different intracellular signaling with clinical importance, some of which has been the basis for development of different calcineurin inhibitors. In this review, the cAMP-dependent calcineurin bio-signaling, protein-protein interactions and their physiological implications as well as regulatory signaling within the context of cellular secretion are explored.