Treatment of osteoporosis with human parathyroid peptide and observations on effect of sodium fluoride.

OBJECTIVE--To evaluate the need for a randomised study of treatment of spinal osteoporosis with human parathyroid peptide in the secondary prevention of crush fractures; to study the effect of human parathyroid hormone peptide 1-34 plus sex hormones on vertebral body cancellous bone; and, separately, to determine the effect of relatively low doses of sodium fluoride plus calcium on spinal bone mineral density. DESIGN--Open study of patients with primary or postmenopausal osteoporosis. All patients had serial bone densitometry of the spine by quantitative computed tomography and dual photon absorptiometry as well as serial densitometry of the radial midshaft (cortical) and radial distal (trabecular) bone by quantitative computed tomography. Changes in the spinal bone not forming the spongiosa of the vertebral bodies ("cortical" bone) were determined from the difference between the two axial measurements, after correction to the same units of measurement. SETTING--Northwick Park Hospital and Medical Research Council Clinical Research Centre. PATIENTS--24 Patients who fulfilled the conventional criteria for type 1 (vertebral) osteoporosis not secondary to recognised causes other than sex hormone deficiency and with at least one crush or wedge vertebral fracture and a spinal bone density (quantitative computed tomography) less than 80 mg/cm3 or two or more fractures. Twelve patients received human parathyroid peptide and 12 sodium fluoride; they were not randomised. MAIN OUTCOME MEASURES--Trends in axial and peripheral bone mass values determined by linear, time dependent regression analyses. RESULTS--The patients receiving the peptide showed a substantial increase in vertebral spongiosa (mean 25.6 mg/cm2 two years after the start of treatment). No significant changes were seen in spinal cortical or radial bone density. The patients receiving sodium fluoride showed roughly equal increases in cancellous and cortical bone over the same period (mean increase in vertebral spongiosa 16.1 mg/cm3). No significant changes were seen in radial bone. CONCLUSIONS--Treatment of postmenopausal women with human parathyroid peptide selectively increases spinal cancellous bone density by amounts that may prove useful in secondary prevention. Peptide treatment should now be tested in a randomised study in which the important end point is prevention of fractures as the usefulness of sodium fluoride in this context is doubtful.     

NADH content in type I and type II human muscle fibres after dynamic exercise.

The effect of dynamic exercise on the NADH content of human type I (slow-twitch) and II (fast-twitch) muscle fibres was investigated. Muscle biopsy samples were obtained from the quadriceps femoris of seven healthy subjects at rest and after bicycle exercise at 40, 75 and 100% of the maximal oxygen uptake [VO2(max.)]. At rest and after exercise at 100% VO2(max.), muscle NADH content was significantly higher (P less than 0.05) in type I than in type II fibres. After exercise at 40% VO2(max.), muscle NADH decreased in type I fibres (P less than 0.01), but was not significantly changed in type II fibres. After exercise at 75 and 100% VO2(max.), muscle NADH increased above the value at rest in both type I and II fibres (P less than 0.05). Muscle lactate was unchanged at 40% VO2(max.), but increased 20- and 60-fold after exercise at 75 and 100% VO2(max.) respectively. The finding that NADH decreased only in type I fibres at 40% VO2(max.) supports the idea that type I is the fibre type predominantly recruited during low-intensity exercise. The increase of NADH in both fibre types after exercise at 75% and 100% VO2(max.) suggests that the availability of oxygen relative to the demand is decreased in both fibre types at high exercise intensities.     

Accuracy and response-time distributions for decision-making: linear perfect integrators versus nonlinear attractor-based neural circuits

Animals choose actions based on imperfect, ambiguous data. “Noise” inherent in neural processing adds further variability to this already-noisy input signal. Mathematical analysis has suggested that the optimal apparatus (in terms of the speed/accuracy trade-off) for reaching decisions about such noisy inputs is perfect accumulation of the inputs by a temporal integrator. Thus, most highly cited models of neural circuitry underlying decision-making have been instantiations of a perfect integrator. Here, in accordance with a growing mathematical and empirical literature, we describe circumstances in which perfect integration is rendered suboptimal. In particular we highlight the impact of three biological constraints: (1) significant noise arising within the decision-making circuitry itself; (2) bounding of integration by maximal neural firing rates; and (3) time limitations on making a decision. Under conditions (1) and (2), an attractor system with stable attractor states can easily best an integrator when accuracy is more important than speed. Moreover, under conditions in which such stable attractor networks do not best the perfect integrator, a system with unstable initial states can do so if readout of the system’s final state is imperfect. Ubiquitously, an attractor system with a nonselective time-dependent input current is both more accurate and more robust to imprecise tuning of parameters than an integrator with such input. Given that neural responses that switch stochastically between discrete states can “masquerade” as integration in single-neuron and trial-averaged data, our results suggest that such networks should be considered as plausible alternatives to the integrator model.     

Effects of agents affecting Ca2+ homeostasis onTrichoderma viride growth and conidiation

Agents known to influence Ca²⁺ homeostasis affected significantly the vegetative growth and starvation-induced conidiation ofTrichoderma viride. Ca²⁺ in millimolar concentrations stimulated both growth and conidiation; a Ca²⁺ deprivation of the fungus by the chelation of extracellular Ca²⁺ (not Mg²⁺ or divalent trace metals) with EGTA (ethyleneglycolbis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid) restricted both the vegetative growth rate and starvation-induced conidiation. Both processes were affected by either Ca²⁺ or EGTA with different efficiencies. Divalent cations (Sr²⁺, Ba²⁺, Co²⁺, Ni²⁺, Mg²⁺, Cd²⁺, Cu²⁺, Mn²⁺) and La³⁺ (inorganic Ca²⁺ blockers) in millimolar concentrations exerted complex (stimulatory, inhibitory, or biphasic) effects on growth and conidiation. In general, their effects on the two processes were mutually different either qualitatively, or quantitatively, or both. Organic Ca²⁺ antagonists (verapamil and dihydropyridines) inhibited the vegetative growth. The results show that Ca²⁺ is required for vegetative growth and conidiation, and that different Ca²⁺-dependent mechanisms may be involved in the two processes. Divalent cations could serve as a tool for investigating the relationship between growth and conidiation.     

Structure-function relationships in the integument of Salamandra salamandra during ontogenetic development

Morphological, cytological and transport properties of the integument of Salamandra salamandra were investigated during natural ontogenetic development, from birth to adult. Three stages were operationally defined: I, larvae, from birth to metamorphosis; II, metamorphosis (judged externally by the colour change and loss of the gills); and III, post-metamorphosis to adult. Pieces of skin were fixed at various stages for immunocytochemical examinations, and the electrical properties were investigated on parallel pieces. Distinct cellular changes take place in the skin during metamorphosis, and lectin (PNA, WGA and ConA) binding indicates profound changes in glycoprotein composition of cell membranes, following metamorphosis. Band 3 and carbonic anhydrase I (CA I) were confined to mitochondria-rich (MR)-like cells, and were detected only in the larval stage. CA II on the other hand, was detected both in MR-like and in MR cells following metamorphosis. The electrical studies show that the skin becomes more tight (transepithelial resistance increases) upon metamorphosis, followed by manifestation of amiloride-sensitive short-circuit current (I(SC)) indicating that functional Na+ uptake has been acquired. The skin of metamorphosed adults had no finite transepithelial Cl- conductance, and band 3 was not detected in its MR cells. The functional properties of MR-like and MR cells remain to be established.     

Vanadate inhibits the production and/or release of secondary metabolites without impairing growth in several fungal species

Vanadate (NaVO₃) in concentrations between 0.1–3.0 mmol/L inhibited the production of secondary metabolites (SMs) of strains of the following species:Trichoderma viride, Penicillium purpurogenum, Penicillium citrinum, Talaromyces avellaneus, andVerticillium psalliotœ. Growth was either not affected by NaVO₃, or the inhibition of the SM production occurred at lower NaVO₃, concentrations than that of the growth. Thus, at some NaVO₃ concentration the SM production was inhibited but the growth remained unaffected. The results suggest that NaVO₃ exerts a specific action either on the SM biosynthetic pathway(s) or on the export of SMs from cells.     

Assessing SSU rDNA Barcodes in Foraminifera: A Case Study using Bolivina quadrata

The Small Subunit Ribosomal RNA gene (SSU rDNA) is a widely used tool to reconstruct phylogenetic relationships among foraminiferal species. Recently, the highly variable regions of this gene have been proposed as DNA barcodes to identify foraminiferal species. However, the resolution of these barcodes has not been well established, yet. In this study, we evaluate four SSU rDNA hypervariable regions (37/f, 41/f, 43/e, and 45/e) as DNA barcodes to distinguish among species of the genus Bolivina, with particular emphasis on Bolivina quadrata for which ten new sequences ( KY468817 – KY468826 ) were obtained during this study. Our analyses show that a single SSU rDNA hypervariable sequence is insufficient to resolve all Bolivina species and that some regions (37/f and 41/f) are more useful than others (43/e and 45/e) to distinguish among closely related species. In addition, polymorphism analyses reveal a high degree of variability. In the context of barcoding studies, these results emphasize the need to assess the range of intraspecific variability of DNA barcodes prior to their application to identify foraminiferal species in environmental samples; our results also highlight the possibility that a longer SSU rDNA region might be required to distinguish among species belonging to the same taxonomic group (i.e. genus).     

Axonal shortening and the mechanisms of axonal motility

Axons in tissue culture retract and shorten if their tips are detached from the substrate. The shortening reaction of the axon involves contractile forces that also arise during normal axonal motility, elongation, and retraction. We studied shortening in axonal segments isolated from their parent axons by transecting the axon between the growth cone and the most distal point of adhesion to the substrate. Within 15-20 minutes after transection, an isolated axonal segment shortened and pulled its tail end toward the growth cone. During the shortening process, long sinusoidal bends arose along the axon. The identical shortening reaction occurs without transection, when the axon tip is detached from the substrate. Pharmacological studies with inhibitors of glycolysis indicate that the shortening mechanisms utilize metabolic energy, presumably ATP. The rate of sinusoidal shortening is similar to both the rate of polymer translocation in the axon by slow axonal transport and the rate of normal axonal elongation. Taxol inhibits the shortening reaction with a similar dose dependence to its inhibition of axonal growth. Together, all these observations suggest that the same basic intracellular motility mechanisms are involved in normal axonal growth, in slow axonal transport, and in the shortening reaction: the intracellular dynamic system that utilizes ATP to generate longitudinal movements of polymers within the axon may be the same mechanism underlying both the retraction and the elongation of the axon.