Generation of a Xenopus laevis F1 albino J strain by genome editing and oocyte host-transfer

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Developmental Biology 426 (2017): 188–193, doi:10.1016/j.ydbio.2016.03.006.Completion of the Xenopus laevis genome sequence from inbred J strain animals has facilitated the generation of germline mutant X. laevis using targeted genome editing. In the last few years, numerous reports have demonstrated that TALENs are able to induce mutations in F0 Xenopus embryos, but none has demonstrated germline transmission of such mutations in X. laevis. In this report we used the oocyte host-transfer method to generate mutations in both tyrosinase homeologs and found highly-penetrant germline mutations; in contrast, embryonic injections yielded few germline mutations. We also compared the distribution of mutations in several F0 somatic tissues and germ cells and found that the majority of mutations in each tissue were different. These results establish that X. laevis J strain animals are very useful for generating germline mutations and that the oocyte host-transfer method is an efficient technique for generating mutations in both homeologs.This work was supported by grants from the NIH (OD010997 and HD084409)

Xenopus as a model for GI/pancreas disease

Author Posting. © The Author(s), 2015. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Current Pathobiology Reports 3 (2015): 137-145, doi:10.1007/s40139-015-0076-0.Diseases affecting endodermal organs like the pancreas, lung and gastrointestinal (GI) tract have a substantial impact on human welfare. Since many of these are congenital defects that arise as a result of defects during development broad efforts are focused on understanding the development of these organs so as to better identify risk factors, disease mechanisms and therapeutic targets. Studies implementing model systems, like the amphibian Xenopus, have contributed immensely to our understanding of signaling (e.g. Wnt, FGF, BMP, RA) pathways and gene regulation (e.g. hhex, ptf1a, ngn3) that underlie normal development as well as disease progression. Recent advances in genome engineering further enhance the capabilities of the Xenopus model system for pursuing biomedical research, and will undoubtedly result in a boom of new information underlying disease mechanisms ultimately leading to advancements in diagnosis and therapy.2016-04-0

Esperanza y satisfacción con la vida: probando los roles mediadores de la autoestima en tres culturas asiáticas

The relationship between well-being and the personal strength of hope has been elaborated by the identification of internal (self) and external (family, peers, spiritual) locus-of-hope dimensions. Du, Bernardo, and Yeung (2015) showed that self-esteem (personal and relational) mediates the relationship between locus-of-hope and life satisfaction. Locus-of-hope’s goal-related thoughts involve self-evaluation that may either enhance or diminish self-worth, which then influences life satisfaction. We tested the mediated model in three cultural groups: Malaysians, Macau Chinese, and Filipinos. Participants completed scales measuring locus-of-hope, personal and relational self-esteem, and life satisfaction. Path analysis showed significant indirect effects in all cultures: (a) internal locus-of-hope on life satisfaction, mediated by personal self-esteem, and (b) external-family locus-of-hope on life satisfaction, mediated by relational self-esteem. Other significant indirect effects were found in specific cultural groups. Cross-cultural similarities and differences are discussed with reference to how distinct cultures give different meanings to forms of agency associated with the personal strength of hope, creating distinct pathways towards life satisfaction.

Differential structural remodelling of heparan sulfate by chemokines: the role of chemokine oligomerization

Chemokines control the migration of cells in normal physiological processes and in the context of disease such as inflammation, autoimmunity and cancer. Two major interactions are involved: (i) binding of chemokines to chemokine receptors, which activates the cellular machinery required for movement; and (ii) binding of chemokines to glycosaminoglycans (GAGs), which facilitates the organization of chemokines into haptotactic gradients that direct cell movement. Chemokines can bind and activate their receptors as monomers; however, the ability to oligomerize is critical for the function of many chemokines in vivo. Chemokine oligomerization is thought to enhance their affinity for GAGs, and here we show that it significantly affects the ability of chemokines to accumulate on and be retained by heparan sulfate (HS). We also demonstrate that several chemokines differentially rigidify and cross-link HS, thereby affecting HS rigidity and mobility, and that HS cross-linking is significantly enhanced by chemokine oligomerization. These findings suggest that chemokine–GAG interactions may play more diverse biological roles than the traditional paradigms of physical immobilization and establishment of chemokine gradients; we hypothesize that they may promote receptor-independent events such as physical re-organization of the endothelial glycocalyx and extracellular matrix, as well as signalling through proteoglycans to facilitate leukocyte adhesion and transmigration

Elucidating the CXCL12/CXCR4 Signaling Network in Chronic Lymphocytic Leukemia through Phosphoproteomics Analysis

, and is thought to be due to enhanced survival signaling responses to environmental factors that protect CLL cells from spontaneous and chemotherapy-induced death. Although normally associated with cell migration, the chemokine, CXCL12, is one of the factors known to support the survival of CLL cells. Thus, the signaling pathways activated by CXCL12 and its receptor, CXCR4, were investigated as components of these pathways and may represent targets that if inhibited, could render resistant CLL cells more susceptible to chemotherapy.To determine the downstream signaling targets that contribute to the survival effects of CXCL12 in CLL, we took a phosphoproteomics approach to identify and compare phosphopeptides in unstimulated and CXCL12-stimulated primary CLL cells. While some of the survival pathways activated by CXCL12 in CLL are known, including Akt and ERK1/2, this approach enabled the identification of additional signaling targets and novel phosphoproteins that could have implications in CLL disease and therapy. In addition to the phosphoproteomics results, we provide evidence from western blot validation that the tumor suppressor, programmed cell death factor 4 (PDCD4), is a previously unidentified phosphorylation target of CXCL12 signaling in all CLL cells probed. Additionally, heat shock protein 27 (HSP27), which mediates anti-apoptotic signaling and has previously been linked to chemotherapeutic resistance, was detected in a subset (∼25%) of CLL patients cells examined.Since PDCD4 and HSP27 have previously been associated with cancer and regulation of cell growth and apoptosis, these proteins may have novel implications in CLL cell survival and represent potential therapeutic targets. PDCD4 also represents a previously unknown signaling target of chemokine receptors; therefore, these observations increase our understanding of alternative pathways to migration that may be activated or inhibited by chemokines in the context of cancer cell survival

How to conduct culturally sensitive and ethically sound research when studying sensitive topics in non-WEIRD contexts

This How-to Guide offers action points for researchers to critically reflect on in order to examine how their identities and roles impact research processes. It advocates for more inclusive research practices by encouraging researchers to think thoroughly about socioeconomic inequalities, power dynamics, and language-related issues. Such intersectional issues become particularly salient when conducting research with participants demographically different from us, and/or in non-WEIRD (Western, Educated, Industrialized, Rich, and Democratic) contexts. The first two authors are Philippine-born academics; one is a tenured, mid-career academic based in the Philippines, and the other is an early career researcher based in the UK; both are experienced in broad international collaborations, using largely mixed methodologies, in cultural, social, and personality psychology topics. The third author is from North America, working long-term in UK academia on topics of stereotyping, prejudice, and adult learning inclusion. Drawing on our collective experience, we provide research examples and practical suggestions that researchers may find useful for engaging in critical reflexivity and developing more inclusive research designs, and data collection and analyses processes

A Cross-Cultural Study of Justice Sensitivity and Its Consequences for Cooperation

In Western samples, individuals differ systematically in the importance they assign to matters of justice and injustice, and dispositional Justice Sensitivity can be differentiated according to the perspectives of victim, observer, beneficiary, and perpetrator. In a cross-cultural comparison between the Philippines, Germany, and Australia (N ¼ 677 students), we investigated whether Justice Sensitivity can be equivalently described by these four perspectives, whether measurement instruments have invariant psychometric properties, and whether the psychological relevance of the Justice Sensitivity perspectives for cooperation behavior differs between these cultural contexts. The results of multigroup confirmatory factor analyses support weak measurement invariance and invariant associations between Justice Sensitivity perspectives and trust game decisions. Across cultures, victim sensitivity predicted reluctance to cooperate under threat of exploitation, and observer, beneficiary, and perpetrator sensitivities predicted cooperation under temptation. Our study extends insight into Justice Sensitivity to underresearched cultural contexts of urban and rural Philippines