Modeling complex neutrophil dynamics in the grey collie

We have developed a mathematical model for the peripheral regulation of neutrophil production mediated by granulocyte colony-stimulating factor. We have used that model to show that the pattern of neutrophil oscillations in nine grey collies is consistent with the hypothesis that cyclical neutropenia is due to an oscillatory stem cell input to the neutrophil regulatory system, and not due to autonomous oscillations in the peripheral neutrophil regulatory system. In the process of interfacing our model with the laboratory data, we have estimated parameters for the peripheral neutrophil control system consistent with higher than normal apoptotic cell loss within the recognizable neutrophil precursors. This is in agreement with other experimental data. Our estimated model parameters also predict that the peripheral neutrophil production system is globally stable in the grey collies we studied. This further supports our hypothesis that the origin of the oscillatory behavior in cyclical neutropenia is in the stem cell population, consistent with other clinical and experimental evidence.     

Antitrypanosomal and cysteine protease inhibitory activities of alkyldiamine cryptolepine derivatives

Cryptolepine derivatives containing alkyldiamine side-chains, 2, with potent inhibitory activity against Trypanosoma brucei brucei are reported. Compounds 2 showed improved activity and selectivity to T. b. brucei when compared to the lead compound. The most selective compound, 2k, presents a selectivity index value of 6200 and an IC(50) of 10nM against the parasite. These derivatives are also potent inhibitors of the trypanosome papain-like cysteine proteases cruzain, which could, at least in part, explain their antitrypanosomal activity. Overall, these compounds with good antitrypanosomal activity and selectivity provide an encouraging starting point for the rational design of new and effective antitrypanosomal agents.     

Impacts of feral horses in the Australian Alps and evidence‐based solutions

New evidence of impacts by feral horses in Australia's alpine parks systems confirms they endanger threatened species and extensively damage critically endangered bog communities that could take millennia to recover. These impacts are not confounded by effects of deer and accumulate over time, even when only a small number of feral horses (~100) are present. With protected areas representing only a small proportion of the area of the Australian states of New South Wales (9.3%) and Victoria (17%), allowing feral horses to degrade reserves is not a reasonable management compromise, is contrary to the purpose of the protected area system and conflicts with international obligations. Modelling and decades of management experience indicate that trapping alone does not control feral horse numbers. Trapping and fertility control can work in small populations, but not when there are several thousand horses in remote areas. Aerial culling is needed to cost‐effectively and humanely control feral horse populations. The relatively small amount of suffering feral horses experience during a cull is outweighed by (i) avoiding suffering and death of horses from starvation and thirst, (ii) avoiding the suffering of native animals displaced by horses and (iii) avoiding the ethical concerns of driving threatened species towards extinction. Objections to aerial culling on welfare and cultural grounds are contradicted by evidence. Improving knowledge in the general community about what is at stake is long overdue because without this knowledge, small groups with vested interests and unfounded claims have been able to dominate debate and dictate management actions. As a result of ineffective management, horse populations are now expanding and causing well‐documented damage to Australia's alpine parks, placing at risk almost $10M spent on restoration after livestock grazing ended. The costs of horse control and restoration escalate the longer large horse populations remain in the alpine parks. It is crucial that feral horse numbers are rapidly reduced to levels where ecosystems begin to recover. Aerial culling is needed as part of the toolbox to achieve that reduction.     

OCP3 is an important modulator of NPR1-mediated jasmonic acid-dependent induced defenses in <Emphasis Type="Italic">Arabidopsis</Emphasis>

Background  

Upon appropriate stimulation, plants increase their level of resistance against future pathogen attack. This phenomenon, known as induced resistance, presents an adaptive advantage due to its reduced fitness costs and its systemic and broad-spectrum nature. In Arabidopsis, different types of induced resistance have been defined based on the signaling pathways involved, particularly those dependent on salicylic acid (SA) and/or jasmonic acid (JA).     

Dynamic hematological disease: a review

We review the basic characteristics of four periodic hematological disorders (periodic auto-immune hemolytic anemia, cyclical thrombocytopenia, cyclical neutropenia and periodic chronic myelogenous leukemia) and examine the role that mathematical modeling and numerical simulations have played in our understanding of the origin of these diseases and in the regulation of hematopoiesis.     

Cytochemical demonstration of hydrogen peroxide in polymorphonuclear leukocyte phagosomes

Phagocytosis by polymorphonuclear leukocytes (PMN) is accompanied by specific morphological and metabolic events which may result in the killing of internalized micro-organism. Hydrogen peroxide is produced in increased amounts during phagocytosis (17) and in combination with myeloperoxidase and halide ions constitute a potent, microbicidal mechanism (8,9,11). There can be direct iodination of micro-organisms (10), or alternatively, other intermediate reaction products, i.e. chloramines and aldehydes (21), can exert a microbicidal effect. The H2O2-peroxidase-halide system is presumed to operate within the phagocytic vacuole (12,18). Myeloperoxidase, present in the primary granules of PMN, enters the phagocytic vacuole during degranulation (1,4,7), and halide ions are probably derived from the extracellular medium or are present in the PMN (see 11, 18). For the operation of this system in intact cells, the presence of H2O2 in the phagocytic vacuole is necessary, and indeed this has been suggested by the work of several investigators (12, 18, 21). In the present investigation, the diaminobenzidine reaction of Graham and Karnovsky (5), modified to utilize endogenous myeloperoxidase and hydrogen peroxide, has been applied to actively phagocytizing PMN to demonstrate cytochemically the presence of H2O2 in the phagocytic vacuole.     

Phylogenetic Analysis of the Mitochondrial Genomes from Leber Hereditary Optic Neuropathy Pedigrees

The nucleotide sequences of the mitochondrial genomes from patients with Leber hereditary optic neuropathy (LHON) were used for phylogenetic analysis to study the origin and population history of pathogenic mitochondrial mutations. Sequences of both the coding region (8300 bp) and the more rapidly evolving noncoding control region (1300 bp) were analyzed. Patients with the primary LHON mutations at nucleotides 3460, 11,778, and 14,484 were included in this study, as were LHON patients and non-LHON controls that lacked these primary mutations; some of the subjects also carried secondary LHON mutations. The phylogenetic analyses demonstrate that primary LHON mutations arose and were fixed multiple times within the population, even for the small set of LHON patients that was analyzed in these initial studies. In contrast, the secondary LHON mutations at nucleotides 4216, 4917, and 13,708 arose once: the mitochondrial genomes that carried these secondary mutations formed a well supported phylogenetic cluster that apparently arose 60,000 to 100,000 years ago. Previous studies found secondary LHON mutations at a higher frequency among LHON patients than among control subjects. However, this finding does not prove a pathogenetic role of these mutations in LHON. Instead, the increased frequency is more likely to reflect the population genetic history of secondary mutations relative to that of primary LHON mutations.     

DNA Extraction from small blood volumes and the processing of cellulose blood cards for use in polymerase chain reaction

This article describes two procedures for the purification of genomic DNA from small blood volumes of whole blood using DNAzol^®BD. In the first procedure, DNA is isolated from 1–20 μL of whole blood using a fast and simple protocol that is appropriate for the simultaneous extraction of a large number of samples. The isolated DNA is suitable for gel electrophoresis and polymerase chain reaction (PCR). In the second procedure, cellulose blood cards containing approx 5 μL of dried blood are treated with DNAzol BD in order to retain DNA on the cellulose matrix while removing other cellular components. The blood card with DNA subsequently serves as template in PCR. The blood card processing and amplification procedures are performed in the same PCR tube without any centrifugation steps, making the combined procedures amenable for automated DNA preparation and amplification in a single tube.     

A mathematical analysis of microbial inactivation at linearly rising temperatures: calculation of the temperature rise needed to kill Listeria monocytogenes in different foods and methods for dynamic measurements of D and z values

From a theoretical analysis of the inactivation of microbes heated at linearly rising temperatures an equation was derived for predicting the linear temperature rise needed to reduce viable numbers of microbes by any chosen factor. This equation is used to predict the temperatures needed to inactivate Listeria monocytogenes in different foods based on published D and z values. Two novel mathematical methods for deriving D and z values from viable counts obtained at linearly rising temperatures are also presented.