Inhibition of gap junction and adherens junction assembly by connexin and A-CAM antibodies

We examined the roles of the extracellular domains of a gap junction protein and a cell adhesion molecule in gap junction and adherens junction formation by altering cell interactions with antibody Fab fragments. Using immunoblotting and immunocytochemistry we demonstrated that Novikoff cells contained the gap junction protein, connexin43 (Cx43), and the cell adhesion molecule, A-CAM (N-cadherin). Cells were dissociated in EDTA, allowed to recover, and reaggregated for 60 min in media containing Fab fragments prepared from a number of antibodies. We observed no cell-cell dye transfer 4 min after microinjection in 90% of the cell pairs treated with Fab fragments of antibodies for the first or second extracellular domain of Cx43, the second extracellular domain of connexin32 (Cx32) or A-CAM. Cell-cell dye transfer was detected within 30 s in cell pairs treated with control Fab fragments (pre-immune serum, antibodies to the rat major histocompatibility complex or the amino or carboxyl termii of Cx43). We observed no gap junctions by freeze-fracture EM and no adherens junctions by thin section EM between cells treated with the Fab fragments that blocked cell-cell dye transfer. Gap junctions were found on approximately 50% of the cells in control samples using freeze-fracture EM. We demonstrated with reaggregated Novikoff cells that: (a) functional interactions of the extracellular domains of the connexins were necessary for the formation of gap junction channels; (b) cell interactions mediated by A-CAM were required for gap junction assembly; and (c) Fab fragments of antibodies for A-CAM or connexin extracellular domains blocked adherens junction formation

Phosphorylation of MCPH1 isoforms during mitosis followed by isoform‐specific degradation by APC/C‐CDH1

Microcephalin‐1 (MCPH1) exists as 2 isoforms that regulate cyclin‐dependent kinase‐1 activation and chromosome condensation during mitosis, with MCPH1 mutations causing primary microcephaly. MCPH1 is also a tumor suppressor protein, with roles in DNA damage repair/checkpoints. Despite these important roles, there is little information on the cellular regulation of MCPH1. We show that both MCPH1 isoforms are phosphorylated in a cyclin‐dependent kinase‐1–dependent manner in mitosis and identify several novel phosphorylation sites. Upon mitotic exit, MCPH1 isoforms were degraded by the anaphase‐promoting complex/cyclosome–CDH1 E3 ligase complex. Anaphase‐promoting complex/cyclosome–CDH1 target proteins generally have D‐Box or KEN‐Box degron sequences. We found that MCPH1 isoforms are degraded independently, with the long isoform degradation being D‐Box dependent, whereas the short isoform was KEN‐Box dependent. Our research identifies several novel mechanisms regulating MCPH1 and also highlights important issues with several commercial MCPH1 antibodies, with potential relevance to previously published data.—Meyer, S. K., Dunn, M., Vidler, D. S., Porter, A., Blain, P. G., Jowsey, P. A. Phosphorylation of MCPH1 isoforms during mitosis followed by isoform‐specific degradation by APC/C‐CDH1. FASEB J. 33, 2796–2808 (2019). www.fasebj.or

Development and evaluation of Research-driven Information Systems

We propose to create a methodological framework that can be applied to evaluate Research-driven Information Systems (RdIS) in aconsistent way. This is done by picking those examples of RdISs that have been evaluatedproperly and making those evaluation processes standard. Our proposed methodologicalframework for the evaluation of RdISs can assist IS researchers in selecting the appropriateevaluation methods. Further exploration of the characteristics of RdISs has led to a betterunderstanding on suitable methods to evaluate the potential applicability of RdISs in practice.A study of IS literature revealed that the evaluation of RdISs should be interpretive andmulti-method of nature. An RdIS that was developed in our research group is evaluatedusing a method that was designed with the new methodological knowledge

Parasite Infection, Carcinogenesis and Human Malignancy.

Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in areas holoendemic for malaria. The initiation of Plasmodium falciparum related endemic Burkitt lymphoma requires additional transforming events induced by the Epstein-Barr virus. Observations suggest that Strongyloides stercoralis may be a relevant co-factor in HTLV-1-related T cell lymphomas. This review provides an overview of the mechanisms of parasitic infection-induced carcinogenicity

Hepatic effects of tartrazine (E 102) after systemic exposure are independent of oestrogen receptor interactions in the mouse

Tartrazine is a food colour that activates the transcriptional function of the human oestrogen receptor alpha in an in vitro cell model. Since oestrogens are cholestatic, we hypothesised tartrazine will cause periportal injury to the liver in vivo. To test this hypothesis, tartrazine was initially administered systemically to mice resulting in a periportal recruitment of inflammatory cells, increased serum alkaline phosphatase activity and mild periportal fibrosis. To determine whether an oestrogenic effect may be a key event in this response, tartrazine, sulphonated metabolites and a food additive contaminant were screened for their ability to interact with murine oestrogen receptors. In all cases, there were no interactions as agonists or antagonists and further, no oestrogenicity was observed with tartrazine in an in vivo uterine growth assay. To examine the relevance of the hepatic effects of tartrazine to its use as a food additive, tartrazine was orally administered to transgenic NF-κB-Luc mice. Pre- and concurrent oral treatment with alcohol was incorporated given its potential to promote gut permeability and hepatic inflammation. Tartrazine alone induced NF- κB activities in the colon and liver but there was no periportal recruitment of inflammatory cells or fibrosis. Tartrazine, its sulphonated metabolites and the contaminant inhibited sulphotransferase activities in murine hepatic S9 extracts. Given the role of sulfotransferases in bile acid excretion, the initiating event giving rise to periportal inflammation and subsequent hepatic pathology through systemic tartrazine exposure is therefore potentially associated an inhibition of bile acid sulphation and excretion and not on oestrogen receptor-mediated transcriptional function. However, these effects were restricted to systemic exposures to tartrazine and did not occur to any significant effect after oral exposure

Why polymer chains in a melt are not random walks

A cornerstone of modern polymer physics is the `Flory ideality hypothesis' which states that a chain in a polymer melt adopts `ideal' random-walk-like conformations. Here we revisit theoretically and numerically this pivotal assumption and demonstrate that there are noticeable deviations from ideality. The deviations come from the interplay of chain connectivity and the incompressibility of the melt, leading to an effective repulsion between chain segments of all sizes $s$. The amplitude of this repulsion increases with decreasing $s$ where chain segments become more and more swollen. We illustrate this swelling by an analysis of the form factor $F(q)$, i.e. the scattered intensity at wavevector $q$ resulting from intramolecular interferences of a chain. A `Kratky plot' of $q^2F(q)$ {\em vs.} $q$ does not exhibit the plateau for intermediate wavevectors characteristic of ideal chains. One rather finds a conspicuous depression of the plateau, $\delta(F^{-1}(q)) = |q|^3/32\rho$, which increases with $q$ and only depends on the monomer density $\rho$.Comment: 4 pages, 4 figures, EPL, accepted January 200

Non-Abelian Excitations of the Quark-Gluon Plasma

We present new, non-abelian, solutions to the equations of motion which describe the collective excitations of a quark-gluon plasma at high temperature. These solutions correspond to spatially uniform color oscillations.Comment: 8 pages LaTex, 1 figure (not included; available upon request), Saclay preprint T94/0

Two New Candidate Planets in Eccentric Orbits

Doppler measurements of two G-type main-sequence stars, HD210277 and HD168443, reveal Keplerian variations that imply the presence of companions with masses (M sin i) of 1.28 and 5.04 M_Jup and orbital periods of 437 d and 58 d, respectively. The orbits have large eccentricities of e=0.45 and e=0.54, respectively. All 9 known extrasolar planet candidates with a=0.2-2.5 AU have orbital eccentricities greater than 0.1, higher than that of Jupiter (e=0.05). Eccentric orbits may result from gravitational perturbations imposed by other orbiting planets or stars, by passing stars in the dense star-forming cluster, or by the protoplanetary disk. Based on published studies and our near-IR adaptive optics images, HD210277 appears to be a single star. However, HD168443 exhibits a long-term velocity trend consistent with a close stellar companion, as yet undetected directly.Comment: AASTeX, 31 pages including 10 Postscript figures, to appear in the Astrophysical Journal (July 1999

Applying the Theory of Planned Behavior to Sedentariness and Stress

Objective: The purpose of this study was to evaluate the predictive value of the theory of planned behavior (TPB) in the sedentary behavior (SB) of young and middle-aged U.S. adults. Relationships between SB over a six-week period were examined using socio-demographic characteristics, TPB constructs, and a stress variable. Methods: Participants (n=45, mean age=31 years, 70% female, 83% White) completed surveys that included sociodemographic information, TPB constructs, and the Weekly Stress Inventory. Participants wore an activity monitor for six weeks and completed the stress inventory once weekly over the study period. A longitudinal model was estimated to determine the relationship between TPB constructs, socio-demographic characteristics, and stress level with SB across the six weeks. Results: Activity monitors revealed participants were sedentary for approximately 11 waking hours per day (SD=1.4). Bivariate analyses indicated a small effect between subjective norms and SB. Model fit indices modestly supported TPB constructs in explaining SB (i.e., a 2.3% reduction in person-level error variance); and a modest relationship between greater stress and less SB (i.e., additional 1.4% reduction in person-level error variance). Conclusions: Results cautiously support continued exploration of the TPB in SB research. Like most behaviors, the TPB alone may not fully explain SB. Future research should continue to explore theoretical determinants of SB, expand to include other theoretical models; and include diverse populations. More research is needed to understand the relationship between SB and stress. Practitioners are encouraged to consider both SB and stress in holistic efforts to improve the health of adults