Phylogenetic diversification of immunoglobulin genes and the antibody repertoire

Immunoglobulins are encoded by a large multigene system that undergoes somatic rearrangement and additional genetic change during the development of immunoglobulin-producing cells. Inducible antibody and antibody-like responses are found in all vertebrates. However, immunoglobulin possessing disulfide-bonded heavy and light chains and domain-type organization has been described only in representatives of the jawed vertebrates. High degrees of nucleotide and predicted amino acid sequence identity are evident when the segmental elements that constitute the immunoglobulin gene loci in phylogenetically divergent vertebrates are compared. However, the organization of gene loci and the manner in which the independent elements recombine (and diversify) vary markedly among different taxa. One striking pattern of gene organization is the "cluster type" that appears to be restricted to the chondrichthyes (cartilaginous fishes) and limits segmental rearrangement to closely linked elements. This type of gene organization is associated with both heavy- and light-chain gene loci. In some cases, the clusters are "joined" or "partially joined" in the germ line, in effect predetermining or partially predetermining, respectively, the encoded specificities (the assumption being that these are expressed) of the individual loci. By relating the sequences of transcribed gene products to their respective germ-line genes, it is evident that, in some cases, joined-type genes are expressed. This raises a question about the existence and/or nature of allelic exclusion in these species. The extensive variation in gene organization found throughout the vertebrate species may relate directly to the role of intersegmental (V<==>D<==>J) distances in the commitment of the individual antibody-producing cell to a particular genetic specificity. Thus, the evolution of this locus, perhaps more so than that of others, may reflect the interrelationships between genetic organization and function.      

Norepinephrine effects on identified neurons of the rat dorsal motor nucleus of the vagus

The dorsal motor nucleus of the vagus (DMV) receives more noradrenergic terminals than any other medullary nucleus; few studies, however, have examined the effects of norepinephrine (NE) on DMV neurons. Using whole cell recordings in thin slices, we determined the effects of NE on identified gastric-projecting DMV neurons. Twenty-five percent of DMV neurons were unresponsive to NE, whereas the remaining 75% responded to NE with either an excitation (49%), an inhibition (26%), or an inhibition followed by an excitation (4%). Antrum/pylorus- and corpus-projecting neurons responded to NE with a similar percentage of excitatory (49 and 59%, respectively) and inhibitory (20% for both groups) responses. A lower percentage of excitatory (37%) and a higher percentage of inhibitory (36%) responses were, however, observed in fundus-projecting neurons. In all groups, pretreatment with prazosin or phenylephrine antagonized or mimicked the NE-induced excitation, respectively. Pretreatment with yohimbine or UK-14304 antagonized or mimicked the NE-induced inhibition, respectively. These data suggest that NE depolarization is mediated by alpha(1)-adrenoceptors, whereas NE hyperpolarization is mediated by alpha(2)-adrenoceptors. In 16 neurons depolarized by NE, amplitude of the action potential afterhyperpolarization (AHP) and its kinetics of decay (tau) were significantly reduced vs. control. No differences were found on the amplitude and tau of AHP in neurons hyperpolarized by NE. Using immunohistochemical techniques, we found that the distribution of tyrosine hydroxylase fibers within the DMV was significantly different within the mediolateral extent of DMV; however, distribution of cells responding to NE did not show a specific pattern of localization.     

What can we learn from noncoding regions of similarity between genomes?

Background  

In addition to known protein-coding genes, large amounts of apparently non-coding sequence are conserved between the human and mouse genomes. It seems reasonable to assume that these conserved regions are more likely to contain functional elements than less-conserved portions of the genome.     

Musings on the wanderer: what's new in our understanding of vago-vagal reflexes? III. Activity-dependent plasticity in vago-vagal reflexes controlling the stomach

Vago-vagal reflex circuits modulate digestive functions from the oral cavity to the transverse colon. Previous articles in this series have described events at the level of the sensory receptors encoding the peripheral stimuli, the transmission of information in the afferent vagus, and the conversion of this data within the dorsal vagal complex (DVC) to impulses in the preganglionic efferents. The control by vagal efferents of the postganglionic neurons impinging on the glands and smooth muscles of the target organs has also been illustrated. Here we focus on some of the mechanisms by which these apparently static reflex circuits can be made quite plastic as a consequence of the action of modulatory inputs from other central nervous system sources. A large body of evidence has shown that the neuronal elements that constitute these brain stem circuits have nonuniform properties and function differently according to status of their target organs and the level of activity in critical modulatory inputs. We propose that DVC circuits undergo a certain amount of short-term plasticity that allows the brain stem neuronal elements to act in harmony with neural systems that control behavioral and physiological homeostasis.     

Receptors and transmission in the brain-gut axis: potential for novel therapies. V. Fast and slow extrinsic modulation of dorsal vagal complex circuits

Vago-vagal reflex circuits in the medulla are responsible for the smooth coordination of the digestive processes carried out from the oral cavity to the transverse colon. In this themes article, we concentrate mostly on electrophysiological studies concerning the extrinsic modulation of these vago-vagal reflex circuits, with a particular emphasis on two types of modulation, i.e., by "fast" classic neurotransmitters and by "slow" neuromodulators. These examples review two of the most potent modulatory processes at work within the dorsal vagal complex, which have dramatic effects on gastrointestinal function. The reader should be mindful of the fact that many more different inputs from other central nervous system (CNS) loci or circulating humoral factors add to this complex mix of modulatory inputs. It is likely that similar long-term modulations of synaptic transmission occur with other neurotransmitters and may represent an important mechanism for the integration and regulation of neuronal behavior. Of course, this fact strongly militates against the success of any single drug or approach in the treatment of motility disorders having a CNS component.     

An interlaboratory comparison of physiological and genetic properties of four Saccharomyces cerevisiae strains

To select a Saccharomyces cerevisiae reference strain amenable to experimental techniques used in (molecular) genetic, physiological and biochemical engineering research, a variety of properties were studied in four diploid, prototrophic laboratory strains. The following parameters were investigated: 1) maximum specific growth rate in shake-flask cultures; 2) biomass yields on glucose during growth on defined media in batch cultures and steady-state chemostat cultures under controlled conditions with respect to pH and dissolved oxygen concentration; 3) the critical specific growth rate above which aerobic fermentation becomes apparent in glucose-limited accelerostat cultures; 4) sporulation and mating efficiency; and 5) transformation efficiency via the lithium-acetate, bicine, and electroporation methods. On the basis of physiological as well as genetic properties, strains from the CEN.PK family were selected as a platform for cell-factory research on the stoichiometry and kinetics of growth and product formation.     

Regulation of fermentative capacity and levels of glycolytic enzymes in chemostat cultures of Saccharomyces cerevisiae

Regulation of fermentative capacity was studied in chemostat cultures of two Saccharomyces cerevisiae strains: the laboratory strain CEN.PK113-7D and the industrial bakers’ yeast strain DS28911. The two strains were cultivated at a fixed dilution rate of 0.10 h⁻¹ under various nutrient limitation regimes: aerobic and anaerobic glucose limitation, aerobic and anaerobic nitrogen limitation on glucose, and aerobic ethanol limitation. Also the effect of specific growth rate on fermentative capacity was compared in glucose-limited, aerobic cultures grown at dilution rates between 0.05 h⁻¹ and 0.40 h⁻¹. Biomass yields and metabolite formation patterns were identical for the two strains under all cultivation conditions tested. However, the way in which environmental conditions affected fermentative capacity (assayed off-line as ethanol production rate under anaerobic conditions) differed for the two strains. A different regulation of fermentative capacity in the two strains was also evident from the levels of the glycolytic enzymes, as determined by in vitro enzyme assays. With the exception of phosphofructokinase and pyruvate decarboxylase in the industrial strain, no clear-cut correlation between the activities of glycolytic enzymes and the fermentative capacity was found. These results emphasise the need for controlled cultivation conditions in studies on metabolic regulation in S. cerevisiae and demonstrate that conclusions from physiological studies cannot necessarily be extrapolated from one S. cerevisiae strain to the other.