Virion conformational forms and the complex inactivation kinetics of echovirus by chlorine in water

Aberrant inactivation kinetics were observed when monodispersed echovirus type 1 (Farouk) was inactivated with chlorine. An initial 1- to 2-log10-unit decrease in titer was followed by lag period, during which the titer stayed the same or increased, and this was followed by a final decline in titer. First-order kinetics were obtained with poliovirus type 1 under the same conditions. Isoelectric focusing studies of echovirus before chlorine treatment showed that the virus distributed into two pH-dependent and interconvertible isoelectric forms. After chlorine treatment all remaining virus infectivity was associated with a third pH-independent isoelectric form. The complex inactivation kinetics appeared to be due to shifts between these conformational forms during inactivation in certain ionic environments. Under certain conditions the conformational shifts resulted in substantial resistance of monodispersed echovirus to chlorine.     

Interleukin-1-β and Tumor Necrosis Factor-α Increase Peripheral-Type Benzodiazepine Binding Sites in Cultured Polygonal Astrocytes

Peripheral-type benzodiazepine binding sites (PTBBS) are markedly increased in the injured CNS. Astrocytes appear to be the primary cell type which express increased PTBBS. Because certain cytokines within the injured CNS are potent mitogens for astrocytes, we examined the effects of two such cytokines, interleukin (IL)-1 beta and tumor necrosis factor (TNF), on PTBBS in cultured astrocytes using [3H]Ro 5-4864 as the specific ligand. Purified cultures of either polygonal or process-bearing astrocytes were prepared from neonatal rat cerebral hemispheres. At a concentration of 1.8 nM, specific binding of the radioactive ligand to polygonal astrocytes reached equilibrium within 60 min and was half-maximal by 5-10 min. By contrast, specific binding to process-bearing astrocytes barely exceeded background levels. IL-1 and TNF increased PTBBS within polygonal astrocytes in both dose- and time-dependent manners. At 10-50 ng/ml, IL-1 beta and TNF-alpha elevated [3H]Ro 5-4864 binding in polygonal astrocyte cultures 65 and 87%, respectively, above the level in control cultures. However, no changes in PTBBS were seen within polygonal astrocytes after IL-2 treatment. Scatchard analysis of saturation binding experiments suggested that the increase in PTBBS promoted by TNF was due to an increased number of binding sites present in polygonal astrocytes and not due to an increase in receptor affinity. Binding data suggested that PTBBS within cultures of process-bearing astrocytes were virtually absent irrespective of the treatment. These in vitro data suggest that certain cytokines found in the injured brain may be involved in up-regulating PTBBS within a particular subtype of astrocyte.     

Anti-Inflammatory Effects of Acupuncture Stimulation via the Vagus Nerve

Although acupuncture therapy is widely used in traditional Asian medicine for the treatment of diverse internal organ disorders, its underlying biological mechanisms are largely unknown. Here, we investigated the functional involvement of acupuncture stimulation (AS) in the regulation of inflammatory responses. TNF-α production in mouse serum, which was induced by lipopolysaccharide (LPS) administration, was decreased by manual acupuncture (MAC) at the zusanli acupoint (stomach36, ST36). In the spleen, TNF-α mRNA and protein levels were also downregulated by MAC and were recovered by using a splenic neurectomy and a vagotomy. c-Fos, which was induced in the nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus nerve (DMV) by LPS and electroacupuncture (EAC), was further increased by focal administration of the AMPA receptor blocker CNQX and the purinergic receptor antagonist PPADS. TNF-α levels in the spleen were decreased by CNQX and PPADS treatments, implying the involvement of inhibitory neuronal activity in the DVC. In unanesthetized animals, both MAC and EAC generated c-Fos induction in the DVC neurons. However, MAC, but not EAC, was effective in decreasing splenic TNF-α production. These results suggest that the therapeutic effects of acupuncture may be mediated through vagal modulation of inflammatory responses in internal organs.     

On the necessity of an archetypal concept in morphology: With special reference to the concepts of “structure” and “homology”

Morphological elements, or structures, are sorted into four categories depending on their level of anatomical isolation and the presence or absence of intrinsically identifying characteristics. These four categories are used to highlight the difficulties with the concept of structure and our ability to identify or define structures. The analysis is extended to the concept of homology through a discussion of the methodological and philosophical problems of the current concept of homology. It is argued that homology is fundamentally a similarity based concept rather than a phylogenetic concept, and a proposal is put forth to return to a comparative context for homology. It is shown that for both the concepts of structure and homology ana priori assumption of stable underlying patterns (i.e. archetypes) is essential.