Neuroethology has pregnant agendas

Two of the many agendas of neuroethology are illustrated with examples. The first issue is what cells or assemblies of cells and what patterns of activity are sufficient to accomplish recognition of ethologically important stimulus configurations and initiation of behavioral action. The theme is the opportunities available in relatively neglected approaches to these objectives. As an example, the approach is developed of gentle microstimulation of loci in the brain where cells have been found to be responsive to complex, natural stimuli, under conditions conducive to the performance of tell-tale behavior. Other approaches include: (a) microinjection of modulatory substances into regions with such complex recognition cells, and (b) recording in efficient and informative ways, by using multiple electrode arrays, registering wideband activity, in behaving animals. The second issue is what brain and behavior differences has evolution produced between major taxa at distinct grades of complexity. Emphasized are our relative ignorance of basic aspects of connectivity, physiology and cognitive capacities in the major grades and the probability of surprises from new studies that employ comparison. Accepted: 29 January 1999     

Anatomic guided ablation of the atrial right ganglionated plexi is enough for cardiac autonomic modulation in patients with significant bradyarrhythmias

IntroductionCardiac autonomic system modulation by endocardial ablation targeting atrial ganglionated plexi (GP) is an alternative strategy in selected patients with severe functional bradyarrhythmias, although no consensus exists on the best ablation strategy. The aim of this study was to evaluate if a simplified approach by a purely anatomical guided ablation of just the atrial right GP is enough for the treatment of these patients.MethodsWe prospectively enrolled patients with significant functional bradyarrhythmias and performed endocardial ablation purely guided by 3D electroanatomic mapping directed at the atrial right GP and accessed parameters of parasympathetic modulation and recurrence of bradyarrhythmias.ResultsThirteen patients enrolled (76.9% male, median age 51, 42–63 years). After ablation, a median RR interval shortening of 28.3 (25.6–40.3)% occurred (1111, 937.5–1395.4 ms to 722.9, 652.2–882.4 ms, p = 0.0002). The AH interval also shortened (19, 10.5–35.7%) significantly after the procedure (115, 105–122 ms to 85, 71–105 ms, p = 0.0023) as well as Wenckebach cycle length (11.1, 5.9–17.8% shortening) from 450, 440–510 ms to 430, 400–460 ms, p = 0.0127. On 24-h Holter monitoring there was significant increase in heart rates (HR) of patients after ablation (minimal HR increased from 34 (26–43)bpm to 49 (43–56)bpm, p = 0,0102 and mean HR from 65 (47–72)bpm to 78 (67–87)bpm, p = 0.0004). No patients had recurrence of symptoms or significant bradyarrhythmias during a median follow-up of 8.4 months.ConclusionsA purely anatomic guided procedure directed only at the atrial right ganglionated plexi seems to be enough as a therapeutic approach for cardioneuroablation in selected patients with significant functional bradyarrhythmias.     

State-dependent responses of two motor systems in the crayfish,Pacifastacus leniusculus

The expression of both swimmeret and postural motor patterns in crayfish (Pacifastacus leniusculus) were affected by stimulation of a second root of a thoracic ganglion. The response of the swimmeret system depended on the state of the postural system. In most cases, the response of the swimmeret system outlasted the stimulus.Stimulation of a thoracic second root also elicited coordinated responses from the postural system, that outlasted the stimulus. In different preparations, either the flexor excitor motor neurones or the extensor excitor motor neurones were excited by this stimulation. In every case, excitation of one set of motor neurones was accompanied by inhibition of that group's functional antagonists.This stimulation seemed to coordinate the activity of both systems; when stimulation inhibited the flexor motor neurones, then the extensor motor neurones and the swimmeret system were excited. When stimulation excited the flexor motor neurones, then the extensor motor neurones and the swimmeret system were inhibited.Two classes of interneurones that responded to stimulation of a thoracic second root were encountered in the first abdominal ganglion. These interneurones could be the pathway that coordinates the response of the postural and swimmeret systems to stimulation of a thoracic second root.Abbreviations TSR thoracic second root - epsp excitatory post-synaptic potential - ipsp inhibitory post-synaptic potential - EJP excitatory jonctional potential - PS power-stroke - RS return-stroke - INT interneurone - N1 first segmental nerve - N2 second segmental nerve - N3 third segmental nerve - A1 abdominal ganglion 1     

Asymmetric hydrolysis of dimethyl 3-phenylglutarate catalyzed by Lecitase Ultra: Effect of the immobilization protocol on its catalytic properties

The asymmetric hydrolysis of dimethyl 3-phenylglutarate (1) by different immobilized preparations of a phospholipase A₁ (Lecitase Ultra (LECI)) at pH 7 and 25 °C has been studied. Agarose beads coated with octyl, cyanogen bromide (CNBr), polyethylenimine (PEI) or glyoxyl groups were used as supports for the immobilization of LECI. The different derivatives behaved very differently in terms of activity, discrimination between 1 and methyl 3-phenylglutarate (2) resulting from the hydrolysis of 1, enantioselectivity (in the hydrolysis of 1 to produce R or S-2) and enantiospecificity in the hydrolysis of R-2 and S-2. Using 1 mM of 1, CNBr-LECI showed the highest activity (13 × 10⁻³ μmol/min mg protein) while octyl-LECI was about 20 times less active. All the enzyme preparations mainly produced (S)-2, but with different enantioselectivity. CNBr-Lecitase was the most enantioselective, producing the S-2 10 fold more rapidly than the R-2, while octyl-Lecitase gave only half of that difference.LECI adsorbed on octyl-agarose allowed to get a yield up to 99% of S-2 (ee was 66%). The reaction stopped in the monoester and no isomer of this compound was further hydrolyzed by the enzyme. However, when the reaction was catalyzed by the other immobilized LECI preparations, the enzyme was able to hydrolyze mainly the minority isomer, permitting to improve the ee of the remaining S-2. The best results were obtained using CNBr-LECI, which gave (S)-methyl-3-phenylglutarate with a yield of 80% and an ee exceeding 99%.     

The ontogeny of feeding behavior and cranial morphology in the leopard shark Triakis semifasciata (Girard 1854): A longitudinal perspective

While much is known about the ecological and functional morphology of feeding in lower vertebrates, studies of elasmobranch feeding over ontogeny are broadly lacking. In this study, the ontogeny of feeding behavior and morphology were investigated in neonatal and young-of-the-year leopard sharks Triakis semifasciata using morphometric measurements of growth and high-speed videography in a longitudinal study. Five food types were used during filming sessions to facilitate differentiation of modulation and variation over ontogeny. Functional aspects of muscle and buccal volume scaling were investigated through dissection. Growth over ontogeny was shown to influence numerous kinematic variables, while intra- and inter-individual variability was the dominant factor affecting feeding behavior. Modulation of feeding behavior based on food size and elusiveness was present for timing variables and predator motion during the strike, but not for food motion or the relative extent of buccal expansion. Allometric growth occurred in all aspects of external cranial morphology measured, resulting in a shallower head profile, anterior displacement of the mouth, and relatively larger jaw musculature over ontogeny. While the degree to which morphology constrains or enhances behavior cannot be directly quantified, variability in behavior greatly exceeds variability in morphology over early ontogeny. Maintenance of a behaviorally and morphologically versatile feeding apparatus throughout ontogeny is proposed to enhance the exploitation of resources and facilitate a diverse diet in T. semifasciata under variable environmental conditions.     

FcγRI blockade and modulation for immunotherapy

 Splenectomy and corticosteroids are the treatment of choice for patients with immune thrombocytopenic purpura (ITP). However, for the 10%–15% of patients who do not respond to conventional therapy, high-dose i.v. IgG can induce life-saving transient responses. The benefits of i.v. IgG have been attributed to Fc receptor blockade; however, the involvement of the individual Fc receptors for IgG (FcγR) in ITP remain to be more completely defined. Recently a mAb, designated mAb H22, which recognizes an epitope on FcγRI (CD64) outside the ligand-binding domain, was humanized. Because mAb H22 is a human IgG1 and FcγRI has a high affinity for human IgG1 antibodies, we predicted that mAb H22 would bind to the FcγRI ligand-binding site through its Fc domain and to its external FcγRI epitope through both Fab domains. These studies demonstrate that mAb H22 blocked FcγRI-mediated phagocytosis of opsonized red blood cells more effectively than an irrelevant IgG. Moreover, cross-linking FcγRI with mAb H22 down-modulated FcγRI expression on monocytes, an effect seen within 2 h. Accepted: 14 October 1997     

Dental mesenchymal stromal/stem cells in different microenvironments— implications in regenerative therapy

Current research data reveal microenvironment as a significant modifier of physical functions, pathologic changes, as well as the therapeutic effects of stem cells. When comparing regeneration potential of various stem cell types used for cytotherapy and tissue engineering, mesenchymal stem cells (MSCs) are currently the most attractive cell source for bone and tooth regeneration due to their differentiation and immunomodulatory potential and lack of ethical issues associated with their use. The microenvironment of donors and recipients selected in cytotherapy plays a crucial role in regenerative potential of transplanted MSCs, indicating interactions of cells with their microenvironment indispensable in MSC-mediated bone and dental regeneration. Since a variety of MSC populations have been procured from different parts of the tooth and tooth-supporting tissues, MSCs of dental origin and their achievements in capacity to reconstitute various dental tissues have gained attention of many research groups over the years. This review discusses recent advances in comparative analyses of dental MSC regeneration potential with regards to their tissue origin and specific microenvironmental conditions, giving additional insight into the current clinical application of these cells.     

Multifunctional role of microRNAs in mesenchymal stem cell-derived exosomes in treatment of diseases

Mesenchymal stem cells can be replaced by exosomes for the treatment of inflammatory diseases, injury repair, degenerative diseases, and tumors. Exosomes are small vesicles rich in a variety of nucleic acids [including messenger RNA, Long non-coding RNA, microRNA (miRNA), and circular RNA], proteins, and lipids. Exosomes can be secreted by most cells in the human body and are known to play a key role in the communication of information and material transport between cells. Like exosomes, miRNAs were neglected before their role in various activities of organisms was discovered. Several studies have confirmed that miRNAs play a vital role within exosomes. This review focuses on the specific role of miRNAs in MSC-derived exosomes (MSC-exosomes) and the methods commonly used by researchers to study miRNAs in exosomes. Taken together, miRNAs from MSC-exosomes display immense potential and practical value, both in basic medicine and future clinical applications, in treating several diseases.     

Gangliosides Inhibit Glucosylceramide Synthase: A Possible Role in Ganglioside Therapy

Gangliosides stimulate the hydrolysis of glucosylceramide (GlcCer), their precursor, and therefore may lower the level of cellular GlcCer and exert a feedback control effect to slow the formation of gangliosides. Tests were made to see if a similar effect on GlcCer levels can be exerted by the action of gangliosides on GlcCer synthesis. Using a new assay procedure, we showed that gangliosides do inhibit the synthase in brain membranes quite effectively, the most active being those lipids with more sugar and sialic acid moieties. Mice injected with a mixture of brain gangliosides for 5 days were found to have a lower level of ceramide:UDP-Glc glucosyltransferase activity in brain, liver, and kidney. The inhibition seems to be exerted by competition for the active site and binding to effector site(s) on the enzyme. It is possible that the reported therapeutic actions of gangliosides on the nervous system are, in part, the result of lowered levels of GlcCer. Malignant tumors shed gangliosides into the extracellular fluid, which are believed to block the generation of antibodies by the host's immunodefense system; this effect also may be due, in part, to reduction in the GlcCer level of immunogenic cells. A new finding is that a ceramide containing phytosphingosine is a markedly better substrate for GlcCer synthase than one containing the more common base.