Systematics within Gyps vultures: a clade at risk

Background  

Populations of the Oriental White-backed Vulture (Gyps bengalensis) have declined by over 95% within the past decade. This decline is largely due to incidental consumption of the non-steroidal anti-inflammatory veterinary pharmaceutical diclofenac, commonly used to treat domestic livestock. The conservation status of other Gyps vultures in southern Asia is also of immediate concern, given the lack of knowledge regarding status of their populations and the continuing existence of taxonomic uncertainties. In this study, we assess phylogenetic relationships for all recognized species and the majority of subspecies within the genus Gyps. The continuing veterinary use of diclofenac is an unknown but potential risk to related species with similar feeding habits to Gyps bengalensis. Therefore, an accurate assessment of the phylogenetic relationships among Gyps vultures should aid in their conservation by clarifying taxonomic uncertainties, and enabling inference of their respective relatedness to susceptible G. bengalensis.     

An automated differential thermal and potentiometric titration apparatus for binding studies

A differential pH-termal titration apparatus is described which can detect pH differences with a sensitivity of ±0.0001 pH units and a thermal sensitivity of ±0.00002°C at a time constant of 0.1 s. With a reaction which yields 1 kcal mol⁻¹, the current system can detect concentrations as low as 4×10⁻⁶ M or, in a 2 ml volume, a total amount of 40 nmol. With a time constant of 0.1 s, the sensitivity is 20±4 μ°C. The experimental protocol is specified by a microprocessor and three modes of operation are possible: titration at constant rate of reagent addition, titration at variable rates of addition so that the contents of both cells are at either constant pH or at a constant temperature and variable rate when a rate of change is specified. Experimental data are collected in files, corrected for heat loss, initial baseline drift, and changes in volume. The final corrected from the standardized run of 0.01338 M HCl in 0.2 M KCl at 25°C calibrate the pH scale yielded the calorimetric conversion constants and pK_w which are calculated and stored for subsequent corrections for the titration of an unknown acid or the measurement of bindin constants and heats.     

Brief Bursts Self-Inhibit and Correlate the Pyramidal Network

Inhibitory pathways are an essential component in the function of the neocortical microcircuitry. Despite the relatively small fraction of inhibitory neurons in the neocortex, these neurons are strongly activated due to their high connectivity rate and the intricate manner in which they interconnect with pyramidal cells (PCs). One prominent pathway is the frequency-dependent disynaptic inhibition (FDDI) formed between layer 5 PCs and mediated by Martinotti cells (MCs). Here, we show that simultaneous short bursts in four PCs are sufficient to exert FDDI in all neighboring PCs within the dimensions of a cortical column. This powerful inhibition is mediated by few interneurons, leading to strongly correlated membrane fluctuations and synchronous spiking between PCs simultaneously receiving FDDI. Somatic integration of such inhibition is independent and electrically isolated from monosynaptic excitation formed between the same PCs. FDDI is strongly shaped by I(h) in PC dendrites, which determines the effective integration time window for inhibitory and excitatory inputs. We propose a key disynaptic mechanism by which brief bursts generated by a few PCs can synchronize the activity in the pyramidal network.     

Effects of nicotinamide on NAD and poly (ADP-ribose) metabolism in DNA-damaged human lymphocytes

The effect of nicotinamide on unscheduled DNA synthesis was studied in resting human lymphocytes. In cells treated with UV irradiation or with MNNG, nicotinamide caused a two-fold stimulation of unscheduled DNA synthesis and retarded the rate of NAD⁺ lowering caused by these treatments. Nicotinamide also reduced the burst of poly(ADP-ribose) synthesis caused by MNNG treat-ment. Thus under conditions that it enhances unscheduled DNA synthesis, nicotinamide causes marked effects on the metabolism of NAD⁺ and poly(ADP-ribose). The effect of nicotinamide on unscheduled DNA synthesis was shown to be independent of protein or polyamine synthesis.     

Chromosomal studies of leukemic and preleukemic Fanconi's anemia patients

Summary Cytogenetic studies of three Fanconi's anemia patients are reported, one of the patients having erythroleukemia, the other two preleukemia. Clonal abnormalities were present in all three cases. Partial chromosomal duplication uncommon in other leukemias was observed. Partial duplication of the long arm of chromosome 3 has been observed in the present case of erythroleukemia examined as well as in a previously reported one.     

Two distinct defects in intracellular growth complemented by a single genetic locus in Legionella pneumophila

Legionella pneumophila mutants specifically defective for intracellular replication were isolated using an intracellular thymineless death enrichment strategy. Mutants belonging to two distinct phenotypic classes were unable to grow in macrophage-like cultured cells. One class of mutants was defective for both inhibition of phagosome–lysosome fusion and association of host cell organelles with bacteria-containing phagosomes (‘recruitment’). Another class of mutants was defective only for organelle recruitment, suggesting that recruitment may be necessary for intracellular growth. Recombinant clones were identified that complemented the intracellular growth defects of these mutants. A single genetic locus, designated dot (for defect in organelle trafficking), restored wild-type phenotypes for intracellular growth, organelle recruitment, and inhibition of phagosome–lysosome fusion to mutants belonging to both phenotypic classes.     

Interleukin-6 and alpha-2-macroglobulin indicate an acute-phase state in Alzheimer's disease cortices.

Recent studies indicated that the formation of a major constituent of Alzheimer's disease (AD) senile plaques, called beta A4-peptide, does not result from normal processing of its precursor, amyloid precursor protein (APP). Since proteolytic cleavage of APP inside its beta A4 sequence was found to be part of APP processing the formation of the beta A4-peptide seems to be prevented under normal conditions. We considered whether in AD one of the endogenous proteinase inhibitors might interfere with APP processing. After we had recently found that cultured human neuronal cells synthesize the most potent of the known human proteinase inhibitors, alpha-2-macroglobulin (alpha 2M), upon stimulation with the inflammatory mediator interleukin-6 (IL-6) we now investigated whether alpha 2M and IL-6 could be detected in AD brains. Here we report that AD cortical senile plaques display strong alpha 2M and IL-6 immunoreactivity while no such immunoreactivity was found in age-matched control brains. Strong perinuclear alpha 2M immunoreactivity in hippocampal CA1 neurons of Alzheimer's disease brains indicates that neuronal cells are the site of alpha 2M synthesis in AD brains. We did not detect elevated IL-6 or alpha 2M levels in the cerebrospinal fluid of AD patients. Our data indicate that a sequence of immunological events which seem to be restricted to the local cortical environment is part of AD pathology.