Lpp is involved in Wnt/PCP signaling and acts together with Scrib to mediate convergence and extension movements during zebrafish gastrulation

The zyxin-related LPP protein is localized at focal adhesions and cell–cell contacts and is involved in the regulation of smooth muscle cell migration. A known interaction partner of LPP in human is the tumor suppressor protein SCRIB. Knocking down scrib expression during zebrafish embryonic development results in defects of convergence and extension (C&E) movements, which occur during gastrulation and mediate elongation of the anterior–posterior body axis. Mediolateral cell polarization underlying C&E is regulated by a noncanonical Wnt signaling pathway constituting the vertebrate planar cell polarity (PCP) pathway. Here, we investigated the role of Lpp during early zebrafish development. We show that morpholino knockdown of lpp results in defects of C&E, phenocopying noncanonical Wnt signaling mutants. Time-lapse analysis associates the defective dorsal convergence movements with a reduced ability to migrate along straight paths. In addition, expression of Lpp is significantly reduced in Wnt11 morphants and in embryos overexpressing Wnt11 or a dominant-negative form of Rho kinase 2, which is a downstream effector of Wnt11, suggesting that Lpp expression is dependent on noncanonical Wnt signaling. Finally, we demonstrate that Lpp interacts with the PCP protein Scrib in zebrafish, and that Lpp and Scrib cooperate for the mediation of C&E.     

Effect of Age-Stiffening Tissues and Intraocular Pressure on Optic Nerve Damages

Age-stiffening of ocular tissues is statistically linked to glaucoma in the elderly. In this study, the effects of age-stiffening on the lamina cribrosa, the primary site of glaucomatous nerve damages, were modeled using computational finite element analysis. We showed that glaucomatous nerve damages and peripheral vision loss behavior can be phenomenologically modeled by shear-based damage criterion. Using this damage criterion, the potential vision loss for 30 years old with mild hypertension of 25mmHg intraocular pressure (IOP) was estimated to be 4%. When the IOP was elevated to 35mmHg, the potential vision loss rose to 45%; and age-stiffening from 35 to 60 years old increased the potential vision loss to 52%. These results showed that while IOP plays a central role in glaucomatous damages, age-stiffening facilitates glaucomatous damages and may be the principal factor that resulted in a higher rate of glaucoma in the elderly than the general population.     

Reactivity of human T-lymphocyte-specific antibodies with peripheral blood mononuclear cells and spleen of Aotus azarae ssp. boliviensis (owl monkey)

Aotus monkeys offer one of the few models that can be used for the evaluation of the immunogenicity and efficacy of new vaccine candidates against the human malarias, Plasmodium falciparum and Plasmodium vivax. However, the tools available for evaluation of the immune responses in these New World primates are still limited. In the present study, a previously selected set of monoclonal antibodies that were raised against human T cell determinants and were reactive with at least one other primate species was investigated for its reactivity with Aotus lymphocytes using FACS analysis, indirect immunofluorescence (IFA) and immunohistochemistry. From a panel of 19 mAb, six were found to react consistently with Aotus lymphocytes using FACS analysis. Further evaluation of the mAb using IFA confirmed these findings. Analysis of the selected mAb on spleen sections of Aotus monkeys identified one anti-CD4 and one anti-CD8 mAb that can be used for immunohistochemical studies. The set of mAb identified in this study can be used for the detection of various T lymphocyte markers in peripheral blood and in tissues of Aotus monkeys. Together with data published by others, mAb are now identified for detection of six different markers of Aotus T lymphocytes. These mAb are very valuable for the characterisation of immune responses after vaccination and infection in the Aotus malaria models.     

Genbank accession #: AJ133707

Plant Molecular Biology -     

Genbank accession #: AJ237597

Plant Molecular Biology -     

Genbank accession #: 133708

Plant Molecular Biology -     

Computational modeling reveals inflammation-driven dilatation of the pulmonary autograft in aortic position

Biomechanics and Modeling in Mechanobiology - The pulmonary autograft in the Ross procedure, where the aortic valve is replaced by the patient’s own pulmonary valve, is prone to failure due...     

Improvement in in?vitro fertilization outcome following in?vivo synchronization of oocyte maturation in mice

Synchronization of oocyte maturation in vitro has been shown to produce higher in vitro fertilization (IVF) rates than those observed in oocytes matured in vitro without synchronization. However, the increased IVF rates never exceeded those observed in oocytes matured in vivo without synchronization. This study was therefore designed to define the effect of in vivo synchronization of oocyte maturation on IVF rates. Mice were superovulated and orally treated with 7.5 mg cilostazol (CLZ), a phosphodiesterase 3A (PDE3A) inhibitor, to induce ovulation of immature oocytes at different stages depending on frequency and time of administration of CLZ. Mice treated with CLZ ovulated germinal vesicle (GV) or metaphase I (MI) oocytes that underwent maturation in vitro or in vivo (i.e. in the oviduct) followed by IVF. Superovulated control mice ovulated mature oocytes that underwent IVF directly upon collection. Ovulated MI oocytes matured in vitro or in vivo had similar maturation rates but significantly higher IVF rates, 2–4 cell embryos, than those observed in control oocytes. Ovulated GV oocytes matured in vitro showed similar maturation rates but significantly higher IVF rates than those observed in control oocytes. However, ovulated GV oocytes matured in vivo had significantly lower IVF rates than those noted in control oocytes. It is concluded that CLZ is able to synchronize oocyte maturation and improve IVF rates in superovulated mice. CLZ may be capable of showing similar effects in humans, especially since temporal arrest of human oocyte maturation with other PDE3A inhibitors in vitro was found to improve oocyte competence level. The capability of a clinically approved PDE3A inhibitor to improve oocyte fertilization rates in mice at doses extrapolated from human therapeutic doses suggests the potential scenario of the inclusion of CLZ in superovulation programs. This may improve IVF outcomes in infertile patients.