Haptoglobin Genotype-dependent Differences in Macrophage Lysosomal Oxidative Injury

The major function of the Haptoglobin (Hp) protein is to control trafficking of extracorpuscular hemoglobin (Hb) thru the macrophage CD163 receptor with degradation of the Hb in the lysosome. There is a common copy number polymorphism in the Hp gene (Hp 2 allele) that has been associated with a severalfold increased incidence of atherothrombosis in multiple longitudinal studies. Increased plaque oxidation and apoptotic markers have been observed in Hp 2-2 atherosclerotic plaques, but the mechanism responsible for this finding has not been determined. We proposed that the increased oxidative injury in Hp 2-2 plaques is due to an impaired processing of Hp 2-2-Hb complexes within macrophage lysosomes, thereby resulting in redox active iron accumulation, lysosomal membrane oxidative injury, and macrophage apoptosis. We sought to test this hypothesis in vitro using purified Hp-Hb complex and cells genetically manipulated to express CD163. CD163-mediated endocytosis and lysosomal degradation of Hp-Hb were decreased for Hp 2-2-Hb complexes. Confocal microscopy using lysotropic pH indicator dyes demonstrated that uptake of Hp 2-2-Hb complexes disrupted the lysosomal pH gradient. Cellular fractionation studies of lysosomes isolated from macrophages incubated with Hp 2-2-Hb complexes demonstrated increased lysosomal membrane oxidation and a loss of lysosomal membrane integrity leading to lysosomal enzyme leakage into the cytoplasm. Additionally, markers of apoptosis, DNA fragmentation, and active caspase 3 were increased in macrophages that had endocytosed Hp 2-2-Hb complexes. These data provide novel mechanistic insights into how the Hp genotype regulates lysosomal oxidative stress within macrophages after receptor-mediated endocytosis of Hb.     

Amöboid bewegliche Pigmentzellen im Epithel des Seeigels Centrostephanus longispinus

Zusammenfassung Für den physiologischen Farbwechsel bei Vertebraten und Evertebraten gilt die Vorstellung, daß eine Pigmentbewegung innerhalb einer formkonstanten Zelle stattfindet. Am Seeigel Centrostephanus longispinus wird nun der Nachweis einer amoeboiden Bewegung von Pigmentzellen geführt: Die Epidermis von Centrostephanus enthält große braune Chromatophoren, die bei Belichtung eine Pigmentdispersion, bei Verdunkelung eine Konzentration des Pigments zeigen. Die Chromatophoren sind außerordentlich stark verzweigte Zellen, deren Arme dicht mit Pigmentgrana erfüllt sind. Im geballten Zustand ist die allgemeine Zellform mehr oder weniger ovoid, wobei die Zellarme eingezogen und dicht um die Zellmitte angeordnet sind. Dispersion des Pigments wird hervorgerufen durch Ausstrecken der pigmentierten Zellarme in den Interzellularraum des umgebenden Gewebes. Innerhalb der Zelle werden filamentöse Elemente nachgewiesen, die vermutlich für die Zellbeweglichkeit verantwortlich sind. — Ferner wird der zelluläre Aufbau des Integuments beschrieben.

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Amoeboid pigment cells in the epithelium of the sea urchin Centrostephanus longispinus A novel colour change mechanism

Summary Rapid colour changes in vertebrate and invertebrate species are considered to be due to movement of pigment granules within pigment cells of constant shape. Evidence is presented in this study to show that an amoeboid movement of chromatophores occurs in the epidermis of the Echinoderm Centrostephanus longispinus. The epidermis in this species contains large brown chromatophores, which display a dispersion of pigment on illumination and its concentration on darkening. The chromatophores are extensively branched cells, and their branches are densely packed with pigment granules. In the state of pigment concentration, the shape of the cell is more or less ovoid, and the cell branches are drawn in and closely arranged around the cell centre. Dispersion is attained by a stretching out of the pigmented cell branches into the intercellular spaces of the surrounding tissue. Within the cell, filamentous elements, which may be functional in the motility of the pigment cell, can be demonstrated.—Additionally the cellular composition of the integument is described.

Mit Unterstützung durch die Deutsche Forschungsgemeinschaft. Frl. A. Mikolaczick danken wir für sorgfältige technische Assistenz.     

MODY 2: Mutation identification and molecular ancestry in a Brazilian family

Maturity Onset Diabetes of the Young (MODY) is a heterogeneous group of genetic diseases characterized by a primary defect in insulin secretion and hyperglycemia, non-ketotic disease, monogenic autosomal dominant mode of inheritance, age at onset less than 25 years, and lack of auto-antibodies. It accounts for 2–5% of all cases of non-type 1 diabetes. MODY subtype 2 is caused by mutations in the glucokinase (GCK) gene. In this study, we sequenced the GCK gene of two volunteers with clinical diagnosis for MODY2 and we were able to identify four mutations including one for a premature stop codon (c.76C>T). Based on these results, we have developed a specific PCR-RFLP assay to detect this mutation and tested 122 related volunteers from the same family. This mutation in the GCK gene was detected in 21 additional subjects who also had the clinical features of this genetic disease. In conclusion, we identified new GCK gene mutations in a Brazilian family of Italian descendance, with one due to a premature stop codon located in the second exon of the gene. We also developed a specific assay that is fast, cheap and reliable to detect this mutation. Finally, we built a molecular ancestry model based on our results for the migration of individuals carrying this genetic mutation from Northern Italy to Brazil.     

Profiling of selected indigenous rice (Oryza sativa L.) landraces of Rarh Bengal in relation to osmotic stress tolerance

A total of ten rare indigenous rice landraces of West Bengal were screened for germination potential and seedling growth under varying concentrations of sodium chloride (NaCl) and polyethylene glycol (PEG) solutions as osmotic stress inducing agents. Among the studied rice landraces Kelas and Bhut Moori showed highest degree of tolerance to induced osmotic stresses. Proline content of the studied lines was also determined. Genetic relationship among the studied rice landraces was assessed with 22 previously reported osmotic stress tolerance linked Simple Sequence Repeat (SSR) markers. The identified allelic variants in form of amplified products size (molecular weight) for each SSR marker were documented to find out allele mining set for the linked markers of the studied genotypes in relation to osmotic stress tolerance. A Microsatellite Panel was constructed for the different allelic forms (size of amplified products) of each used marker. Among 22 SSR markers, ten showed unique alleles in form of single specific amplified product for the studied four genotypes which can be used for varietal identification. Genetic relationship among the studied rice lines was determined and a dendrogram was constructed to reveal their genetic inter-relationship. Polymorphism Information Content (PIC) for each used marker was also calculated for the studied rice lines.     

Mouth colour is a reliable signal of need in begging canary nestlings

Begging passerine chicks display brightly coloured mouths as they solicit food from their parents. Despite a range of hypotheses, the function of vivid nestling mouth colour remains unknown. Here I report that mouth colour functions as a signal of need in canary nestlings, in the days immediately following hatching. Changes in mouth colour accurately reflect a nestling''s state of need: the more food deprived the chick, the more intensely coloured its mouth. In controlled experiments with two nestlings, parents were offered the opportunity to choose which nestling to feed. When the mouth colour of one offspring was artificially reddened using food colouring, parents gave it more food. These results demonstrate a novel function for nestling mouth colour and are consistent with recent models of the resolution of parent–offspring conflict.     

Mutant gene frequencies in cats of the greater London area

Summary The frequencies of seven mutant genes of the domestic cat have been estimated by sampling the population of greater London, specific areas of the capital and adjoining counties. An attempt was made to diversify the method of sampling by concentrating upon certain categories of cats. In addition to the usual sightings of cats in streets and open spaces, surveys were made of cats attending a veterinary clinic, those staying at a boarding cattery, those exhibited in the household pet classes at a cat show and those in rescue centres. Although there are inconsistencies, the general impression from frequencies in present and earlier observations is that the lighter phenotypes (mackerel tabby, blue dilution and orange) are favoured by human preference, as opposed to the darker phenotypes (blotched tabby, black and non-orange). Reasons are discussed for thinking that, while human preference may be a factor in the evolution of the feline polymorphism, it is not the fundamental cause.     

Further results on the survival of a gene represented in a founder population

This paper is concerned with gene survival in a population which may increase without density dependence according to a generalization of the Moran model for haploid individuals. A selective advantage to one allele and the possibility of differential reproductive rates are allowed. Simple conditions are given for ultimate homozygosity to be certain and for the possibility of ultimate polymorphism. The results complement and extend those of Heyde (1981, 1982).     

Intraspecific variation of Eolophiodon laboriense,a basal Lophiodontidae (Mammalia,Perissodactyla) from the early Eocene of Southern France

The Lophiodontidae is an emblematic and well-documented Eocene family of perissodactyls from Western Europe. However, after more than a century and a half of studies, lophiodontids still display a complex systematics associated with blurry intraspecific variation and a poorly known early radiation. The locality of La Borie, located near the city of Toulouse, France, has yielded numerous remains of Eolophiodon laboriense. This abundance of remains allows for the first time the study of the intraspecific variation of a basal lophiodontid. The variation has been investigated for dental and cranio-mandibular characters, notably dental polymorphism, size variation and sexual dimorphism. The intraspecific variation of E. laboriense is high with more than 20 polymorphic characters of the dentition, including many additional crests and conules. This dental polymorphism is similar to the one observed in the Bartonian lophiodontid Lophiodon lautricense. E. laboriense also displays an important degree of sexual dimorphism, with male specimens having broader and longer mandibles with larger canines than females. Despite this high intraspecific variation, the low size variation of teeth and the consistency of diagnostic characters strengthen the validity of the genus Eolophiodon and does not impact the previous lophiodontid phylogeny.     

Rapid Quantification of Phototrophic Microorganisms and their Physiological State through their Colour

Quantification of phototrophic organisms on solid substrata together with their metabolic activity can be assessed easily, reliably and quickly through measurement of the organisms' colour. For that purpose only a chroma meter for solid substrata able to quantify the three components of colour is needed. A correlation between these three components and the number of organisms and their physiological state was demonstrated. The methodology developed here makes it possible to save time and materials in comparison with traditional microbiological methods. Moreover, it is a non-destructive method which can be used directly on site and in site. This characteristic is important when microbial environmental monitoring of cultural heritage is involved.     

Involvement of INF-γ functional single nucleotide polymorphism +874 T/A (rs2430561) in breast cancer risk

According Global Cancer Statistics 2020 GLOBOCAN estimates female breast cancer was found as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), and the fourth leading cause (6.9%) of cancer death among women worldwide. Identification of new diagnostic marker sharply characterize the tumor feature is intensive need. The present work was performed to investigate the involvement of the INF-γ + 874 T/A gene polymorphism in different breast cancer prognostic factors. Polymorphism detection analysis was performed on 163 subjects from breast cancer patients, 79 with inflamed cells of breast patients and 144 controls. The gene polymorphism was detected using the amplification refractory mutation system- polymerase chain reaction method (ARMS-PCR). The distribution of INF-γ T + 874A gene polymorphism shows strong significant association between INF-γ + 874 T/A genotypes TT in BC patients (ORTT: 6.41 [95% CI = 2.72–15.1] P < 0.0001) as well as strong significant association regarding T allele (ORT: 1.99 [95% CI = 1.43–2.76] P < 0.0001) when compared to the healthy control. In ICB group the strong association was noted with INF-γ + 874 T/A genotypes AT genotype (ORAT: 2.28 [95% CI = 1.22–4.29] P = 0.007). From the different histological BC hormonal markers the human epidermal growth factor receptor 2 (HER2) was showing significant association in INF-γ + 874 T/A genotypes TT (P = 0.03) and recessive model (TT versus AA + AT P = 0.03). Concerning different BC prognostic models, the poor prognostic one of luminal B, (ER^+ve PR^+ve Her2^+ve) show significant association in the host INF-γ + 874 T/A genotype (TT, P = 0.03) and recessive model (TT versus AA + AT P = 0.02) when compared to the good prognostic hormonal status luminal A model, (ER^+ve PR^+ve Her2-ve). It seems that this is the first study that interested in correlate the INF-γ + 874 T/A gene polymorphisms in Egyptian BC patients. T allele, TT genotype and recessive model of the INF-γ + 874 T/A gene variants were documented as risk factors for BC pathogenesis. It may be used as practical biomarker to guide the BC carcinogenesis and risk process.