Serial Monogamy as Polygyny or Polyandry?

Applications of sexual selection theory to humans lead us to expect that because of mammalian sex differences in obligate parental investment there will be gender differences in fitness variances, and males will benefit more than females from multiple mates. Recent theoretical work in behavioral ecology suggests reality is more complex. In this paper, focused on humans, predictions are derived from conventional parental investment theory regarding expected outcomes associated with serial monogamy and are tested with new data from a postreproductive cohort of men and women in a primarily horticultural population in western Tanzania (Pimbwe). Several predictions derived from the view that serial monogamy is a reproductive strategy from which males benefit are not supported. Furthermore, Pimbwe women are the primary beneficiaries of multiple marriages. The implications for applications of sexual selection theory to humans are discussed, in particular the fact that in some populations women lead sexual and reproductive lives that are very different from those derived from a simple Bateman-Trivers model.     

Potential of Macrostomum lignano to recover from γ-ray irradiation

Stem cells are the only proliferating cells in flatworms and can be eliminated by irradiation with no damage to differentiated cells. We investigated the effect of fractionated irradiation schemes on Macrostomum lignano, namely, on survival, gene expression, morphology and regeneration. Proliferating cells were almost undetectable during the first week post-treatment. Cell proliferation and gene expression were restored within 1 month in a dose-dependent manner following exposure to up to 150 Gy irradiation. During recovery, stem cells did not cross the midline but were restricted within lateral compartments. An accumulated dose of 210 Gy resulted in a lethal phenotype. Our findings demonstrate that M. lignano represents a suitable model system for elucidating the effect of irradiation on the stem cell system in flatworms and for improving our understanding of the recovery potential of severely damaged stem-cell systems.     

Identification of osteocytes in osteoblast-like cell cultures using a monoclonal antibody specifically directed against osteocytes

Summary The development of a monoclonal antibody, OB 7.3, directed against a cell surface antigenic site on osteocytes is described.Osteoblast-like cells were enzymatically isolated from calvaria of chicken embryos after removal of the periostea. The cells were cultured for 6 days, harvested and used to immunize mice. One of the monoclonal antibodies obtained, OB 7.3, reacted specifically with the cell surface of osteocytes. In frozen sections of bone only osteocytes were stained, all other cells present, including mature osteoblasts, were negative. Liver, kidney, spleen, intestine, bloodvessel and skin were also completely negative. Using the monoclonal OB 7.3, positive cells could be demonstrated in sparse osteoblast-like cell cultures. The OB 7.3 positive cells had a stellate morphology and were therefore identified as osteocytes. They behaved in culture as osteocytes in bone tissue in that they formed a network of cell processes connecting osteocytes with each other or with other neighbouring cells. Monoclonal OB 7.3 offers the possibility of isolating osteocytes thereby providing the means for a detailed study of their biochemical properties.In honour of Prof. P. van Duijn     

Approaches to lung cancer treatment using the CD3E×GP-2-directed Bispecific Monoclonal Antibody BIS-1

 The bispecific monoclonal antibody (bsAb) BIS-1 combines a monoclonal-antibody(mAb)-defined specificity for the CD3 complex, as present on all T lymphocytes, with a mAb-defined specificity for the pancarcinoma/epithelium associated glycoprotein EGP-2. In vitro studies indicate that BIS-1 can direct T lymphocytes to kill EGP-2-positive tumour target cells. T cell pre-activation is necessary for this activity and can be obtained either via incubation of isolated peripheral blood mononuclear cells with CD3 mAb, followed by short culturing in recombinant interleukin-2-containing medium, or via costimulation with CD5- and CD28-based bsAb. Clinical application of BIS-1 was started in a pilot study in which carcinoma patients suffering from malignant ascites or intrapleural effusion were treated. In this study, ex vivo activated autologous lymphocytes were applied locally, i.e. intraperitoneally or intrapleurally, in the presence of BIS-1. Local inflammation and antitumour activity were observed, whereas no or only minor systemic toxicity was seen in these patients. Intravenous administration of BIS-1 F(ab′)2 in combination with subcutaneously given recombinant interleukin-2 (i.v. bsAb/rIL-2 treatment) induced transient but considerable toxicity including peripheral vasoconstriction, dyspnoea and fever with a maximal tolerated dose of 5–8 μg/kg. High plasma concentrations of the inflammatory cytokines tumor necrosis factor α and interferon γ were observed at this dose. Whereas bsAb-dictated antitumour activity could be demonstrated to be present in blood samples of these patients in an in vitro assay, no clear clinical responses were observed. In a rat model it was found that i.v. bsAb/rIL-2 treatment of EGP-2-positive tumours was effective when a low systemic tumour burden was present, suggesting that systemic bsAb/rIL-2 treatment might be effective in situations of minimal residual disease. Accepted: 14 October 1997     

A Dynein Motor Attachment Complex Regulates TGF?/Smad3 Signaling

Our previous results have demonstrated that km23-2 has functions in TGFß signaling that are distinct from those for km23-1. In the current report, we demonstrate that blockade of km23-2 decreased TGFß activation of the human Smad7 promoter Smad7-Luc, an endogenous Smad3-target promoter. Luminescence-based mammalian interaction mapping (LUMIER) analyses showed that TGFß stimulated the interaction of km23-2 preferentially with Smad3, relative to that with Smad2. Size exclusion chromatography experiments revealed that km23-2 and Smad3 were recruited into the same complex after TGFß treatment. Moreover, in the presence of TGFß, but not in the absence, km23-2 was present in early endosomes with the TGFß receptors (TßRs) and Smad3. Collectively, our data indicate that km23-2 is a critical signaling intermediate in a Smad3-dependent TGFß signaling pathway. We also provide evidence of the novel finding that TGFß stimulates the rapid recruitment of the km23-2 dimer to the dynein intermediate chain (DIC) of the dynein complex, whereas a kinase-deficient form of TßRII prevented this interaction. Finally, we demonstrate for the first time that TGFß stimulated not only assembly of the dynein motor attachment complex, but also triggered the tethering of the km23-2-Smad3 cargo to the other dynein components. Thus, our data demonstrate a novel function for km23-2 as a motor receptor to recruit Smad3 to the dynein complex for intracellular transport, thereby mediating Smad3-dependent TGFß signaling.