Immunological characterization of a gammadelta T-cell stimulatory ligand on autologous monocytes

Bovine gammadelta T cells are stimulated to proliferate by autologous monocytes. This is referred to as the autologous mixed leucocyte reaction (AMLR). It has been shown previously that the stimulatory component is constitutively expressed on the monocyte plasma membrane and is a protein or has a protein moiety. Here we showed that gammadelta T-cell responses to the monocytes requires interaction with the T-cell receptor because Fab1 fragments of a monoclonal antibody (mAb) that reacts with the delta chain of the T-cell receptor blocked proliferation in the AMLR. Monocyte molecules involved in stimulation were also characterized further by biochemical and immunological methods. A mAb, named M5, was generated by immunizing mice with bovine monocytes and shown to block the ability of monocytes to stimulate in the AMLR. Treatment of monocytes or monocyte membranes with high salt, chelating agents or phospholipase C did not affect their ability to stimulate gammadelta T-cell proliferation or reactivity with mAb M5 indicating the ability of monocytes to stimulate does not involve peripheral membrane components or a glycosyl-phosphatidylinsositol (GPI)-anchored components. Hence it was concluded that the stimulation occurred as a result of intergral membrane proteins including that recognized by mAb M5. The ligand for mAb M5 was on all bovine monocytes and to a lower level on granulocytes but not on lymphocytes. MAb M5 also reacted with sheep monocytes but not with human monocytes or murine macrophages, in agreement with a previous reports that sheep monocytes but not human or mouse mononuclear phagocytes have the capacity to stimulate bovine gammadelta T cells in in vitro cultures. The level of expression of the M5 ligand was not altered by gamma-irradiation or culture of monocytes with lipopolysaccharide but it was decreased following culture with interferon-gamma-containing cell culture supernatants.     

Evaluation of a confidential method of excluding blood donors exposed to human immunodeficiency virus: studies on hepatitis and cytomegalovirus markers

A confidential self-administered questionnaire was given to all blood donors prior to donation (n = 95,917). The questionnaire describes groups at increased risk of acquired immunodeficiency syndrome (AIDS) and requires the donor to designate his blood either for laboratory purposes or for transfusion. In a previous communication, we reported that donors in the former group had a much higher prevalence of antibody to human immunodeficiency virus (HIV) than age, sex and clinic matched controls or a group of "miscellaneous" donors who did not fill out the form properly. In this communication, we report results of tests for other viral markers performed on the three designation groups, namely laboratory-designated, miscellaneous and controls. We found that the former two groups had a higher prevalence of antibody to hepatitis B surface antigen (anti-HBs), hepatitis B core antigen (anti-HBc) and cytomegalovirus (anti-CMV) than controls, but there were no differences in alanine aminotransferase (ALT) levels among the groups. In addition, the laboratory-designated group had a higher prevalence of hepatitis B surface antigen (HBsAg) than the general donor population. These data indicate that a questionnaire designed to ascertain AIDS high-risk donors is valuable in excluding donors who may be carriers of other viruses as well.     

Bilateral traumatic proximal humerus fractures managed by open reduction and internal fixation with locked plates

Fractures of the proximal humerus are uncommon in young patients.Although bilateral fracture of proximal humerus itself is rare,association with epilepsy and electrocution is frequent.Only one case of traumatic bilateral proximal humerus fracture has been reported in the literature.We report a rare case of bilateral traumatic displaced proximal humerus fractures in a 40 years old male patient,which was treated by means of open reduction and internal fixation with proximal humerus locked pates on both sides and obtained a good functional outcome.     

Differential development of relational memory and pattern separation

Researchers have taken a number of different approaches in their exploration of hippocampal function. One approach seeks to describe hippocampal function by probing the memory representations that the hippocampus supports. Another approach focuses on the role of the hippocampus in pattern separation and completion. Each of these approaches to understanding hippocampal function utilizes a distinct set of specialized tasks, and both of these task sets are known to be sensitive to changes in hippocampal function with age and disease status. But the question remains whether the tasks utilized in these two approaches tap into the same aspects of hippocampal function. We explored this question in the context of hippocampal development. Preadolescent children (N = 73) and young adults (N = 41) completed an identical battery of cognitive tasks consisting of a spatial reconstruction relational memory task, the mnemonic similarity task (MST)—an object‐based pattern separation task, and a novel hybrid task—the Object Discrimination and Distribution (ODD) Task—designed to integrate and simultaneously tax pattern separation and spatial relational memory. Children did not demonstrate impairments in lure discrimination relative to young adults on either the object‐based pattern separation task or for aspects of the ODD task that required pattern separation in the absence of relational memory demands but performed more poorly across aspects of tasks that required relational binding.     

SVEP1 plays a crucial role in epidermal differentiation

SVEP1 is a recently identified multidomain cell adhesion protein, homologous to the mouse polydom protein, which has been shown to mediate cell‐cell adhesion in an integrin‐dependent manner in osteogenic cells. In this study, we characterized SVEP1 function in the epidermis. SVEP1 was found by qRT‐PCR to be ubiquitously expressed in human tissues, including the skin. Confocal microscopy revealed that SVEP1 is normally mostly expressed in the cytoplasm of basal and suprabasal epidermal cells. Downregulation of SVEP1 expression in primary keratinocytes resulted in decreased expression of major epidermal differentiation markers. Similarly, SVEP1 downregulation was associated with disturbed differentiation and marked epidermal acanthosis in three‐dimensional skin equivalents. In contrast, the dispase assay failed to demonstrate significant differences in adhesion between keratinocytes expressing normal vs low levels of SVEP1. Homozygous Svep1 knockout mice were embryonic lethal. Thus, to assess the importance of SVEP1 for normal skin homoeostasis in vivo, we downregulated SVEP1 in zebrafish embryos with a Svep1‐specific splice morpholino. Scanning electron microscopy revealed a rugged epidermis with perturbed microridge formation in the centre of the keratinocytes of morphant larvae. Transmission electron microscopy analysis demonstrated abnormal epidermal cell‐cell adhesion with disadhesion between cells in Svep1‐deficient morphant larvae compared to controls. In summary, our results indicate that SVEP1 plays a critical role during epidermal differentiation.     

Ultra-high vacuum scanning tunneling microscopy and theoretical studies of 1-halohexane monolayers on graphite

A simple model system for the 2D self-assembly of functionalized organic molecules on surfaces was examined in a concerted experimental and theoretical effort. Monolayers of 1-halohexanes were formed through vapor deposition onto graphite surfaces in ultrahigh vacuum. Low-temperature scanning tunneling microscopy allowed the molecular conformation, orientation, and monolayer crystallographic parameters to be determined. Essentially identical noncommensurate monolayer structures were found for all 1-halohexanes, with differences in image contrast ascribed mainly to electronic factors. Energy minimizations and molecular dynamics simulations reproduced structural parameters of 1-bromohexane monolayers quantitatively. An analysis of interactions driving the self-assembly process revealed the crucial role played by small but anisotropic electrostatic forces associated with the halogen substituent. While alkyl chain dispersion interactions drive the formation of a close-packed adsorbate monolayer, electrostatic headgroup forces are found to compete successfully in the control of both the angle between lamella and backbone axes and the angle between surface and backbone planes. This competition is consistent with energetic tradeoffs apparent in adsorption energies measured in earlier temperature-programmed desorption studies. In accordance with the higher degree of disorder observed in scanning tunneling microscopy images of 1-fluorohexane, theoretical simulations show that electrostatic forces associated with the fluorine substituent are sufficiently strong to upset the delicate balance of interactions required for the formation of an ordered monolayer. The detailed dissection of the driving forces for self-assembly of these simple model systems is expected to aid in the understanding of the more complex self-assembly processes taking place in the presence of solvent.     

Obesity and the Neurocognitive Basis of Food Reward and the Control of Intake

With the rising prevalence of obesity, hedonic eating has become an important theme in obesity research. Hedonic eating is thought to be that driven by the reward of food consumption and not metabolic need, and this has focused attention on the brain reward system and how its dysregulation may cause overeating and obesity. Here, we begin by examining the brain reward system and the evidence for its dysregulation in human obesity. We then consider the issue of how individuals are able to control their hedonic eating in the present obesogenic environment and compare 2 contrasting perspectives on the control of hedonic eating, specifically, enhanced control of intake via higher cognitive control and loss of control over intake as captured by the food addiction model. We conclude by considering what these perspectives offer in terms of directions for future research and for potential interventions to improve control over food intake at the population and the individual levels.