A transcriptional network associated with natural variation in Drosophila aggressive behavior

Background  

Aggressive behavior is an important component of fitness in most animals. Aggressive behavior is genetically complex, with natural variation attributable to multiple segregating loci with allelic effects that are sensitive to the physical and social environment. However, we know little about the genes and genetic networks affecting natural variation in aggressive behavior. Populations of Drosophila melanogaster harbor quantitative genetic variation in aggressive behavior, providing an excellent model system for dissecting the genetic basis of naturally occurring variation in aggression.     

Aging in the post-genomic era: simple or complex?

A report on the Third Genetic Effects on Aging Meeting, The Jackson Laboratory, Bar Harbor, Maine, August 4-8, 2000.     

Phylogenetic,toxigenic and virulence profiles of <Emphasis Type="Italic">Alternaria</Emphasis> species causing leaf blight of tomato in Egypt

Species of Alternaria are serious plant pathogens, causing major losses on a wide range of crops. Leaf blight symptoms were observed on tomato leaves, and samples were collected from various regions. Isolation was done from symptomatic tomato leaves, and 15 representatives were selected from a collection of 65 isolates of Alternaria species. The virulence of Alternaria isolates was investigated on detached leaves (DL) and whole plants of tomato cv. Super strain B. A phylogenetic analysis was performed based on three partial gene regions, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the RNA polymerase second largest subunit (RPB2) and the Alternaria major allergen gene (Alt a 1). The potentiality of Alternaria isolates to produce toxins was also investigated on the basis of thin-layer chromatography (TLC). Our investigations revealed that Alternaria isolates showed different levels of virulence either on tomato plants or DL. Based on the phylogeny of three genes, Alternaria isolates encompassed two species of small-spored morphospecies: A. alternata (14 isolates) and A. arborescens (single isolate). The produced toxins varied among Alternaria isolates with tenuazonic acid (TeA) being the most abundant mycotoxin produced by most isolates. This study highlighted on other Alternaria species in Egypt that might represent a serious concern for tomato producers as causal agents of leaf blight over other species, i.e. A. solani.     

An unusual dicentric Y chromosome with a functional centromere with no detectable alpha-satellite

We describe an unusual marker chromosome Y. This marker is present in 5% of the lymphocytes of a dysgenetic woman showing a mosaic karyotype 45,X/46,XY/ 47,XY+mar. Q-banding revealed that the marker was morphologically identical to the Y chromosome of the patient but presented the primary constriction in the heterochromatic region. C-banding confirmed that the heterochromatic region was C-positive; furthermore, it showed two spots in the euchromatic region in a position corresponding to that of the centromere in the normal Y Fluorescence in situ hybridization with the centromere-specific probe pDP 97 and the pancentromeric alpha-satellite probe 2730 failed to detect any signal at the primary constriction site. To improve the characterization of the marker chromosome, hybridization was performed using pDP 105, a probe located on the short arm of the Y chromosome, together with chromosome-Y- specific paint-hybridizing to the single sequence spanning the Y short arm. In both cases, positive signals telomeric to the inactive centromere were observed. Possible mechanisms resulting in the formation of the marker chromosome are discussed.     

Depressed level of natural killer cells in cancer family syndrome

Summary Individuals from kindred with cancer family syndrome (CFS) have an increased genetic risk for the development of adenocarcinoma of the colon as well as of several other organs. Previous studies have suggested that this high occurrence of adenocarcinoma in this as in other hereditary neoplastic syndromes may be correlated to an underlying abnormality in immunological tumor surveillance. In attempt to define a marker that might identify individuals within CFS kindred at risk of developing cancer, we determined natural killer (NK) cell number and NK cell function in affected and healthy members of a CFS family. We studied 13 cancer-affected patients, 20 unaffected but at-risk subjects, 20 healthy subjects and 26 normal individuals matched to the patients with colon cancer on the basis of sex and age. We determined the number of NK cells and their function concurrently, using a monoclonal antibody and a⁵¹Cr-release assay with K562 as target cells. We found that the number of NK cells was significantly (P = 0.00004) reduced in cancer patients as compared with healthy subjects and normal controls. Of the 20 at—risk individuals 9 had levels lower than the norm, while 11 showed normal-values. Consequently, the mean percentage of NK cells of this group does not differ either from that of normal subjects or from that of cancer patients. Mean NK cell function was lower in cancer patients than in healthy members of the CFS family but the differences were not statistically significant. Therefore, the mean NK cell function per single cell, expressed as a ratio between cytotoxicity (LU) and the number of NK1-positive cells, resulted paradoxically in an increase when compared with that of normal subjects. The possible mechanisms for this dichotomy were examined.     

Transcriptional response to alcohol exposure in Drosophila melanogaster

Background  

Alcoholism presents widespread social and human health problems. Alcohol sensitivity, the development of tolerance to alcohol and susceptibility to addiction vary in the population. Genetic factors that predispose to alcoholism remain largely unknown due to extensive genetic and environmental variation in human populations. Drosophila, however, allows studies on genetically identical individuals in controlled environments. Although addiction to alcohol has not been demonstrated in Drosophila, flies show responses to alcohol exposure that resemble human intoxication, including hyperactivity, loss of postural control, sedation, and exposure-dependent development of tolerance.     

A rheumatoid factor paradox: inhibition of rituximab effector function

Introduction

Rituximab (RTX) therapy of rheumatoid arthritis (RA) exhibits enhanced effectiveness in seropositive patients. Using patient sera, we tested if this improved efficacy was associated with enhanced RTX mediated complement-dependent cytotoxicity (RTX-CDC).

Methods

We developed an in vitro assay for RTX-CDC using patient sera and the Daudi human B cell line. Using propidium iodide uptake and flow cytometry, we compared RTX-CDC with rheumatoid factor (RF)+ sera relative to normal volunteer, non-RA and RF- sera. Additional studies examined mixing studies of RF+ and RF- sera, as well as the effect of monoclonal IgA or IgM RF. Finally, the effect of RF on RTX mediated trogocytosis of normal B cells was evaluated.

Results

Using human sera, addition of RTX resulted in rapid and profound (> 50%) Daudi cell death that was complement dependent. Surprisingly, RF+ patient sera exhibited reduced RTX-CDC relative to RF- sera, with an inverse relationship of RTX-CDC and RF titer. Mixing studies indicated the presence of an inhibitor of RTX-CDC in RF+ sera. The addition of monoclonal IgM or IgA RF to RF- sera markedly inhibited RTX-CDC. This effect was specific for RF binding to the Fc portion of RTX as it was not apparent with the F(ab)'' domains of RTX engineered onto IgG3 heavy chain. RF also modestly inhibited RTX mediated trogocytosis.

Conclusions

Contrary to expectations, RF+ sera exhibits reduced RTX-CDC due to the presence of RF. The enhanced efficacy of RTX in seropositive RA patients cannot be attributed to improved B cell depletion through CDC. This result indicates that high RF levels may potentially modulate the efficacy of any therapeutic monoclonal antibody dependent on Fc effector function.     

Heat island effects in urban life cycle assessment: Novel insights to include the effects of the urban heat island and UHI‐mitigation measures in LCA for effective policy making

Urbanization often entails a surge in urban temperature compared to the rural surroundings: the Urban Heat Island (UHI) effect. Such a temperature increase triggers the formation of pollutants worsening the urban air quality. Jointly, bad air quality and UHI affect ecosystems and human health. To alleviate the impacts on the population and the environment, it is crucial to design effective UHI‐mitigation measures. Life Cycle Assessment (LCA) is an assessment tool able to capture the complexity of urban settlements and quantify their impact. Yet, as currently implemented, LCA neglects the interactions between the built environment and the local climate, omitting the resulting impacts. This study reviews the existing literature, showing the lack of studies that organically include interactions between the built environment and local climate in LCA. This forms the basis to identify the unsuitability of the current LCA framework for comprehensively capturing the impact of urban settlements. To overcome this limitation, this research offers a pathway to expand the LCA methodology, indicating the necessity to (a) couple the LCA methodology with climate models or physical relations that quantify the interactions between the local climate and the built environment; (b) include novel impact categories in LCA to address such interactions; and (c) use existing or ad hoc developed characterization factors to assess the impacts related to the UHI effect. The LCA community can build on the frame of reference offered by this research to overcome the current limitations of LCA and enable its use for a comprehensive assessment of the impacts of UHI and its mitigation measures.