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Exoskeleton robots found application in neurorehabilitation, telemanipulation, and power augmentation. The human–robot attachment system of an exoskeleton should transmit all the interaction forces while keeping the anatomical and robotic joint axes aligned. Existing attachment concepts were bounding the performance of modern exoskeletons due to insufficient stiffness for high-performance force control, time-consuming adaption processes, and/or bulkiness. Therefore, we developed an augmented attachment system for a recent fully actuated nine-degree-of-freedom upper limb exoskeleton. The proposed system was compared to a conventional solution in a case study with four participants. The proposed attachment system lowered the relative motion between the human and the robot under static loads for all defined landmarks by 45% on average. The occurrence of undesired contacts in the trials was mitigated by 74%, thus improving conditions for closed-loop force control. Furthermore, the proposed system adapted better to the user's anatomy facilitating more accurate alignment and less obstruction. On average, self-attachment took $\mathbf {43(8.3)}$ $\mathrm{s}$ to don(doff). Thereby, the alignment of anatomic landmarks had typically less than 15 mm offset to a thorough expert alignment, making self-attachment eligible. The augmented attachment system and the insights gained by the case study are expected to enable improvement of the physical human–robot interaction of exoskeletons.

Galectins control cell behavior by acting on different signaling pathways. Most of the biological activities ascribed to these molecules rely upon recognition of extracellular glycoconjugates and establishment of multivalente interactions, which trigger adaptive biological responses. However, galectins are also detected within the cell in different compartments, where their regulatory functions still remain poorly understood. A deeper understanding of the entire galectin signalosome and its impact in cell behavior is therefore essential in order to delineate new strategies to specifically manipulate both galectin expression and function. This review summarizes our current knowledge of the signaling pathways activated by galectins, their glycan dependence and the cellular compartment where they become activated and are biologically relevant.

Mature dendritic cells (mDCs) can trigger the effector functions of natural killer (NK) cells. Knock-out, small-interfering RNA or neutralizing antibodies targeting interleukin 12 (IL-12) subunits revealed a critical role for IL-12 in NK cell interferon γ (IFN-γ) secretion promoted by mDCs. However, NK cell activation by DCs also required direct cell-to-cell contacts. DC-mediated NK cell activation involved the formation of stimulatory synapses between DCs and NK cells. The formation of DC/NK cell conjugates depended on cytoskeleton remodeling and lipid raft mobilization in DCs. Moreover, the disruption of the DC cytoskeleton using pharmacologic agents or the loss-of-function mutation of the Wiskott-Aldrich syndrome protein abolished the DC-mediated NK cell activation. Synapse formation promoted the polarized secretion of preassembled stores of IL-12 by DCs toward the NK cell. The synaptic delivery of IL-12 by DCs was required for IFN-γ secretion by NK cells, as assessed using inhibitors of cytoskeleton rearrangements and transwell experiments. Therefore, the cross-talk between DCs and NK cells is dictated by functional synapses. (Blood. 2004;104:3267-3275)

Ikaros proteins are pleiotropic regulators of hematopoiesis and are critically required for the production of lymphocyte and dendritic cell (DC) lineages in mice. Here, we asked if Ikaros proteins could also play a role in the late stages of dendritic cell differentiation. Nuclear Ikaros proteins were up‐regulated during the in vitro differentiation of human monocytes into mature DC, suggesting potential implications in this process. To address this question, a dominant negative mutant Ikaros isoform IK7 was over‐expressed by retroviral gene transfer in human DC precursor cells, to interfere with the function of Ikaros family members during DC development. Expression of IK7 in CD34+ cells inhibited the production of IL‐12‐producing APCs. The resulting progeny of CD34+ cells and in particular, committed CD1a+ DC or CD14+ cell‐derived DC, expressed low levels of MHC class II antigens and of the CD83 maturation marker on the cell surface. Such IK7‐expressing DC induced naïve allogeneic T cells to produce Th2 cytokines. Our results therefore delineate a new role for Ikaros family members, showing that normal levels of Ikaros proteins are essential in DC to regulate the terminal stages of maturation and the capacity to induce optimal Th1 T cell responses.

Interactions between 4-1BB and its ligand, 4-1BBL, enhance CD8(+) T cell-mediated antiviral and antitumor immunity in vivo. However, mechanisms regulating the priming of CD8(+) T cell responses by 4-1BB remain unclear, particularly in humans. The 4-1BB receptor was undetectable on naive or resting human CD8(+) T cells and induced in vitro by TCR triggering. Naive cord blood cells were therefore primed in vitro against peptides or cellular antigens and then co-stimulated with 4-1BBL or agonistic antibodies. Co-stimulation enhanced effector function such as IFN-gamma production and cytotoxicity by augmenting numbers of antigen-specific and effector CD8(+) T cells. OKT3 responses also showed reduced cell death and revealed that the proliferation of CD8(+) T cells required two independently regulated events. One, the induction of IL-2 production, could be directly triggered by 4-1BB engagement on CD8(+) T cells in the absence of accessory cells. The other, expression of CD25, was induced with variable efficacy by accessory cells. Thus, suboptimal accessory cells and 4-1BB co-stimulation combined their effects to enhance IL-2 production and proliferation. Reduced apoptosis observed after co-stimulation in the presence of accessory cells correlated with increased levels of Bcl-X(L) in CD8(+) T cells, while Bcl-2 expression remained unchanged. Altogether, 4-1BB enhanced expansion, survival and effector functions of newly primed CD8(+) T cells, acting in part directly on these cells. As 4-1BB triggering could be protracted from the TCR signal, 4-1BB agonists may function through these mechanisms to enhance or rescue suboptimal immune responses.

The nucleosome, the basic structure of chromatin and normal product of cell apoptosis, plays a pivotal role both in the induction and the pathogenesis of systemic lupus erythematosus (SLE). Nucleosomes have been found to circulate at high levels in patients with SLE and apoptosis of lymphoid cells is increased during human and murine lupus. In this study, we examined the presence of possible defects in clearance mechanisms of apoptotic cells in murine lupus, and questioned further whether nucleosomes could compromise this phagocytic process. There did not appear to be any intrinsic functional defect of macrophages from young MRL+/+ lupus‐prone mice to recognize and phagocytose apoptotic thymocytes. Nucleosomes, as a mimic of increased cell apoptotsis in vivo, induced a strong, dose‐dependent, inhibition of phagocytosis of apoptotic thymocytes by young, pre‐autoimmune, macrophages of MRL+/+ mice, whereas macrophages of non‐autoimmune C3H mice only exhibited a trend to inhibition. The nucleosome‐elicited inhibitory effect persisted during the development of the autoimmune response and appeared to be specific for the molecular mechanisms involved in macrophage phagocytosis of apoptotic cells. Our data suggest that nucleosome elicited inhibition of phagocytosis of apoptotic cells by MRL+/+ macrophages before the onset of the autoimmune response contribute, in a positive loop, to sustain and/or augment the levels of circulating (and potentially immunogenic) nucleosomes in lupus. J. Leukoc. Biol.64: 774–780; 1998.

Increasing evidence suggests that immune complexes made of anti-nuclear antibodies bound to nucleosomes released from dead cells play an important role in the pathogenesis of lupus nephritis. However, the nature and composition of apoptotic nucleosomes still remain elusive. Since large amounts of nucleosomes are released from cells undergoing apoptosis in hybridoma cellcultures, we used hybridomas secreting anti-DNA and anti-nucleosome antibodies grown in protein-free medium to generate nucleosome/anti-DNA and /anti-nucleosome immune complexes, as well as an irrelevant antibody hybrid-oma to generate free, non-complexed apoptotic nucleosomes. Hybridoma supernatants were fractionated by size-exclusion gel chromatography and eluted fractions with a ratio of A260/A280 >1.2 were pooled and analysed for DNA and histone profiles by gel electrophoresis and immunoblotting. When run on a ‘native’ gel, ‘intact’ apoptotic nucleosomes, free or within anti-nucleosome immune complexes, showed a strikingly reduced size compared with ‘standard’ nucleosomes preparedin vitroby endonuclease digestion of cell nuclei. Nucleosomal DNA (extracted from either free or complexed apoptotic nucleosomes) appeared as a major band of 160–180bp, and had the size of ‘standard’ mononucleosome DNA, suggesting degradation of the histone moiety of apoptotic nucleosomes. Histone immunoblotting revealed degra-dation of histones H3 and H4, which was dramatically enhanced when apoptotic nucleosomes were complexed with an anti-nucleosome antibody. Our results provide direct evidence for abnormal histone composition of apoptotic nucleosomes and suggest that the fine specificity of the complexing antibody has an influence on complexed nucleosome composition.

BACKGROUND & AIMS: Gastrin and cholecystokinin (CCK) are gut-brain peptides, with multiple functions in the gastrointestinal tract mediated through CCK-B-gastrin and CCK-A receptors. The receptor localization is, however, not well established in humans. The aim of this study was to investigate the distribution and pharmacological characteristics of CCK-A and CCK-B receptors in the human upper gastrointestinal tract and compare them with those in the rat and dog. METHODS: CCK receptors were localized by in vitro receptor autoradiography with 125I-[Leu15]gastrin-I and 125I-[D-Tyr-Gly, Nle(28,31)]-CCK 26-33 in stomach and gallbladder. RESULTS: High concentrations of CCK-B-gastrin receptors were detected in the midglandular region of the human fundic mucosa. CCK-A receptors were found in the basal region of the antral and fundic mucosa. CCK-A receptors were also located in the muscularis propria of antrum, fundus, and gallbladder, whereas CCK-B-gastrin receptors were only detected in gastric fundic circular muscle. Two nonpeptide CCK receptor antagonists distinguish both receptor subtypes. Comparisons among humans, dogs, and rats suggest that localization and density of CCK receptor subtypes in the upper gastrointestinal tract are species- dependent. CONCLUSIONS: Localization of CCK receptor subtypes in human upper gastrointestinal tract provides a biochemical and morphological basis for the separate regulatory roles of gastrin and CCK. (Gastroenterology 1997 Apr;112(4):1197-205)

Galectins, a family of glycan-binding proteins, can control tumor progression by promoting transformation, angiogenesis and immune escape. We identified a dynamically regulated ‘galectin signature’, which delineates the progression of prostate cancer, highlighting galectin-1 as an attractive target for anti-angiogenic therapy in advanced stages of the disease.

Presents letters to the editor referencing articles and topics discussed in previous issues. "Wipe Out Weeding Woes," which focused on weed prevention in the garden; "Divide and Conquer," which described garden rooms; "Easy-Grow Edible Container Gardens," which discussed container gardening.