Postsynaptic densities contain a subtype of protein kinase C

Protein kinase C or an isoenzyme thereof appears to be a significant component of postsynaptic densities (PSDs) from rat brain. This cytoskeletal organelle binds 4 beta-phorbol 12,13-dibutyrate (PDBu) with a Bmax of about 20 pmol/mg protein and an apparent Kd of 3.3 nM. Ca2+ and phosphatidyl serine (PS) stimulated the endogenous phosphorylation of a subset of PSD polypeptides with Mr values between 16,000 and 22,000. Finally, a monospecific protein kinase C antibody reacted with a Mr 70,000 PSD polypeptide which migrated on SDS-PAGE slightly ahead of the Mr 77,000 purified enzyme. These data suggest that protein kinase C or a similar enzyme can be integrated into a cytoskeletal system and may play an important role in postsynaptic function.     

Activation of Protein Kinase C by the Capsaicin Analogue Resiniferatoxin in Sensory Neurones

Abstract: Resiniferatoxin and capsaicin are sensory neurone-specific excitotoxins that operate a common cation channel in nociceptors. Resiniferatoxin is structurally similar to capsaicin and to phorbol esters. Specific [³H]-resiniferatoxin binding, which was detected in the membrane ( K _D value 1.8 ± 0.2 n M ) but not cytosolic fraction of rat dorsal root ganglia, could not be displaced by phorbol 12,13-dibutyrate. Conversely, resiniferatoxin did not displace [³H]phorbol 12,13-dibutyrate binding in either the cytosolic or membrane fraction. Resiniferatoxin and capsaicin both caused translocation of protein kinase C in dorsal root ganglion neurones (EC₅₀ value 18 ± 3 n M ). This translocation was greatly reduced but not abolished, in the absence of external Ca²⁺, suggesting that it was secondary to Ca²⁺ entry. Resiniferatoxin also caused direct activation of a Ca²⁺- and lipid-dependent kinase (or kinases) in the cytosolic fraction of dorsal root ganglia, at concentrations (100 n M to 10 µ M ) higher than required for displacement of [³H]resiniferatoxin binding or translocation of protein kinase C. Capsaicin (up to 10 µ M ) was unable to mimic this effect. These data imply that although resiniferatoxin-induced translocation of protein kinase C in dorsal root ganglion neurones was mainly indirect, it also caused direct activation of a protein kinase C-like kinase in these cells.     

From clinical specimens to human cancer preclinical models—a journey the NCI-cell line database—25 years later

The intramural the National Cancer Institute (NCI) and more recently the University of Texas Southwestern Medical Center with many different collaborators comprised a complex, multi-disciplinary team that collaborated to generated large, comprehensively annotated, cell-line related research resources which includes associated clinical, and molecular characterization data. This material has been shared in an anonymized fashion to accelerate progress in overcoming lung cancer, the leading cause of cancer death across the world. However, this cell line collection also includes a range of other cancers derived from patient-donated specimens that have been remarkably valuable for other types of cancer and disease research. A comprehensive analysis conducted by the NCI Center for Research Strategy of the 278 cell lines reported in the original Journal of Cellular Biochemistry Supplement, documents that these cell lines and related products have since been used in more than 14 000 grants, and 33 207 published scientific reports. This has resulted in over 1.2 million citations using at least one cell line. Many publications involve the use of more than one cell line, to understand the value of the resource collectively rather than individually; this method has resulted in 2.9 million citations. In addition, these cell lines have been linked to 422 clinical trials and cited by 4700 patents through publications. For lung cancer alone, the cell lines have been used in the research cited in the development of over 70 National Comprehensive Cancer Network clinical guidelines. Finally, it must be underscored again, that patient altruism enabled the availability of this invaluable research resource.     

Intestinal proteases of free-living and parasitic astigmatid mites

Among arthropod pests, mites are responsible for considerable damage to crops, humans and other animals. However, detailed physiological data on these organisms remain sparse, mainly because of their small size but possibly also because of their extreme diversity. Focusing on intestinal proteases, we draw together information from three distinct mite species that all feed on skin but have separately adapted to a free-living, a strictly ecto-parasitic and a parasitic lifestyle. A wide range of studies involving immunohistology, molecular biology, X-ray crystallography and enzyme biochemistry of mite gut proteases suggests that these creatures have diverged considerably as house dust mites, sheep scab mites and scabies mites. Each species has evolved a particular variation of a presumably ancestral repertoire of digestive enzymes that have become specifically adapted to their individual environmental requirements.     

Marine microbial natural products in antifouling coatings

Ecological problems associated with current antifouling technologies have increased interest in the natural strategies that marine organisms use to keep their surfaces clean and free from fouling. Bacteria isolated from living surfaces in the marine environment have been shown to produce chemicals that are potential antifoulants. Active compounds from the cells and culture supernatant of two bacterial strains, FS‐55 and NudMB50–11, isolated from surface of the seaweed, Fucus serratus, and the nudibranch, Archidoris pseudoargus, respectively, were extracted using solid phase extraction. The extracts were combined with acrylic base paint resin and assayed for antifouling activity by measuring their ability to inhibit the growth of fouling bacteria. These formulations were found to be active against fouling bacteria isolated from marine surfaces. The formulation of antifouling paints that incorporate marine microbial natural products is reported here for the first time. This is a significant advance towards the production of an environmentally friendly antifouling paint that utilises a sustainable supply of natural biodegradable compounds.     

Signaling of Ankle Joint Position by Receptors in Different Muscles

Plots were made of multiunit activity versus ankle joint position for receptors in each of the 12 muscles crossing the cat ankle joint, except peroneus tertius, by recording from populations of afferent fibers in muscle nerves. The discharge was measured 15 or 30 sec after terminating the movements that altered the position of the joint. These recordings were dominated by large-spike activity that would be expected to originate mainly from primary spindle endings. Seven of the 12 muscles also cross other joints. Their responses at a given ankle joint position were so altered by changes in the position of the knee or toe joints that they could not reliably signal the position of the ankle joint. As judged from multiunit recording, receptors in each of the five muscles specific to the ankle joint were influenced by more than one axis of ankle joint displacement.

Single-unit recording from dorsal root filaments was used to determine whether primary or secondary spindle receptors in soleus and tibialis anterior could selectively signal one axis of ankle joint rotation. Individual soleus receptors were tested both on the flexion extension axis and with a combined adduction–eversion movement.

For 38 of the 70 soleus receptors examined (54%), firm adduction–eversion produced a level of activity greater than that caused by 10° of flexion, and for 77% the level of activity was greater than that caused by 5° of flexion. For 168 of the 184 tibialis anterior receptors studied (91%), firm abduction inversion produced a level of activity greater than that caused by 10° of extension. Thus few receptors were found that responded exclusively to one axis of rotation.

One way in which the position of the ankle joint could be specified in the face of multiaxial receptor activity is by examining the receptor discharge from more than one muscle. A suggestion for how the nervous system might do this is given in the discussion.     

Muscular torque generation during imposed joint rotation: torque-angle relationships when subjects' only goal is to make a constant effort

It is a reasonable expectation that voluntarily activated spinal motoneurons will be further excited by increases in spindle afferent activity produced by muscle stretch. Human motor behavior attributed to tonic stretch reflexes and to reflexes recruited by relatively slow joint rotation has been reported from several laboratories. We reinvestigated this issue by rotating the elbow joint over the central portion of its range while subjects focused on keeping their elbow flexion effort constant at one of three different levels and made no attempt to control the position, speed or direction of movement of their forearm. There is evidence that subjects' voluntary motor status is constant under these conditions so that any change in torque would be of involuntary origin. On average, torques rose somewhat and then fell as the elbow was flexed through a range of 80° at 10, 20 and 60°/s and a similar pattern occurred during elbow extension; i.e., both concentric and eccentric torque-angle profiles had roughly similar shapes and neither produced consistent stabilizing cross-range stiffness. The negative stiffness (rising torque) during the early part of a concentric movement and the negative stiffness (falling torque) during the later part of an eccentric movement would not have occurred if a stabilizing stretch reflex had been present. Positive stiffness rarely gave rise to torque changes greater than 20% in either individual or cross-subject averaged data. When angular regions of negative stiffness are combined with regions of low positive stiffness (torque change 10% or less), much of the range of motion was not well stabilized, especially during eccentric movements. The sum of the EMGs from biceps brachii, brachioradialis and brachialis showed a pattern opposite to that expected for a stretch reflex; there was an upward trend in the EMG as the elbow was flexed and a downward trend as the elbow was extended. There was little change in the shape of this EMG-angle relationship with either direction or velocity. The individual EMG-angle relationships were distinctive for each of these three elbow flexor muscles in four of the six subjects; in the remaining two, biceps was distinctive, but brachioradialis and brachialis appeared to be coupled. Although the EMGs of individual muscles were modulated over the angular range, no consistent stretch reflexes could be seen in the individual records. Thus, we could find no clear evidence for stretch reflex stabilization of human subjects maintaining a constant effort. Rather, muscle torque appears to be reflexly modulated across a much used portion of the elbow's angular range so that any appreciable stabilizing stiffness that is sustained for more than fractions of a second is associated with a change in effort.     

A preliminary assessment of congruence between biodiversity patterns in Afrotropical forest birds and forest mammals

Burgess, N., de Klerk, H., Fjeldsá, J., Crowe, T. & Rahbek, R. 2000. A preliminary assessment of congruence between biodiversity patterns in Afrotropical forest birds and forest mammals. Ostrich 71 (1 & 2): 286–291.

Databases compiled for forest birds and forest mammals in the Afrotropics were tested for congruence of overall patterns and hotspots of species richness and endemism. We also looked at how well a near-minimum set of priority areas for one taxon catered for the second taxon. Overall species richness and richness hotspots of forest birds were significantly correlated with those of forest mammals, as was the case for overall endemism. Endemism hotspots for forest birds and mammals were not significantly correlated. The near-minimum set for forest birds represented 136 (76.5%) forest mammal species. The near-minimum set for forest mammals represented 350 (93.62%) forest bird species. However, to represent all forest mammals three times each, 51 grids were needed in addition to the 78 chosen as a near-minimum set for forest birds, and to represent all forest birds three times each, 43 more grids were needed in addition to the 80 selected for forest mammals. There is some congruence between the patterns of richness, endemism and near-minimum sets for forest birds and mammals in the Afrotropics, but the one taxon does not provide the ideal conservation solution for the other. Further refinement of the databases used in this paper would allow for more rigorous testing of congruence between these two groups.