Childlessness is high in the US once again, but this time it’s driven by choice, not poverty.

Recent years have seen a rise in childlessness rates in the US close to levels not seen for more than a century. In new research which examines the drivers of childlessness then and now, Thomas Baudin, David de la Croix and Paula E. Gobbi find that while in the early 20th century poverty meant that many women were forced into having fewer children, better education and higher income for women are now the causes of childlessness

Par-4: An Attractive Target for Cancer Therapy

Lack of early diagnosis, cancer recurrence, metastasis, and adverse side effects are some of the major problems in the treatment of cancers. Par-4, a tumor suppressor protein, is an attractive target for cancer therapy as it selectively kills cancer cells. Cl-Par-4 is the active fragment of Par-4 that enters the nucleus and selectively induces apoptosis in cancer cells. It has also been reported that Par-4 increases the susceptibility of cancer cells to chemotherapy and reverses cancer recurrence. Further, Par-4 has been shown to play a dual role: inhibition of EMT (Epithelial-mesenchymal transition) as well as assistance in the reverse process, thereby lowering the chance of cancer metastasis. Because of these unique properties of Par-4, it offers an attractive target for developing anticancer therapy. However, so far only the C-terminal coiled-coil domain has been studied structurally. Here, we have optimized conditions that will be helpful in the structural determination of cl-Par-4 using NMR and X-ray crystallography.https://digitalcommons.odu.edu/gradposters2023_sciences/1017/thumbnail.jp

Using Dedal to share and reuse distributed engineering design information

The overall goal of the project is to facilitate the reuse of previous design experience for the maintenance, repair and redesign of artifacts in the electromechanical engineering domain. An engineering team creates information in the form of meeting summaries, project memos, progress reports, engineering notes, spreadsheet calculations and CAD drawings. Design information captured in these media is difficult to reuse because the way design concepts are referred to evolve over the life of a project and because decisions, requirements and structure are interrelated but rarely explicitly linked. Based on protocol analysis of the information seeking behavior of designer's, we defined a language to describe the content and the form of design records and implemented this language in Dedal, a tool for indexing, modeling and retrieving design information. We first describe the approach to indexing and retrieval in Dedal. Next we describe ongoing work in extending Dedal's capabilities to a distributed environment by integrating it with World Wide Web. This will enable members of a design team who are not co-located to share and reuse information

Development Policies when Accounting for the Extensive Margin of Fertility

Beyond natural sterility, there are two main types of childlessness: one driven by poverty and another by the high opportunity cost to child-rearing. We argue that taking childlessness and its causes into account matters for assessing the impact of development policies on fertility. We measure the importance of the components of childlessness with a structural model of fertility and marriage. Deep parameters are identified using census data from 36 developing countries. On average, one more year of education decreases poverty-driven childlessness by 0.75 percentage points, but increases opportunity-cost-driven childlessness by 0.57 percentage points from the 9th year of schooling onwards. Neglecting the endogenous response of marriage and childlessness leads to overestimating the effectiveness of family planning policies, except where highly educated mothers are also heavily affected by unwanted births, and to underestimating the effect of promoting gender equality on fertility, except in countries where poverty-driven childlessness is high

Characterization of Cl-Par-4: WT vs. Mutant

Intrinsically disordered proteins (IDPs) play important roles in regulation of cell signaling pathways as well as cellular processes. Dysregulation of these proteins is associated with several human diseases. Prostate apoptosis response-4 (Par-4), a proapoptotic tumor suppressor protein, is categorized as an intrinsically disordered protein and downregulation of this protein has been reported in myriad of cancers including glioma, breast cancers, and prostate cancers. The caspase-cleaved fragment of Par-4 (cl-Par-4) plays an active role in tumor suppression by inhibiting several cell survival pathways. Here, we employed site-directed mutagenesis to introduce a point mutation in the cl-Par-4 wildtype (WT) to generate the D313K cl-Par-4 mutant. We have characterized both the mutant and the WT using various biophysical techniques such as CD, DLS, and NMR to determine the effect of the D313K mutation. The results show that D313K cl-Par-4 attains a compact and well-folded helical conformation, possibly a tetramer, similar to that of the WT in presence of high salt at physiological pH. However, D313K does so with half the amount of salt required for the WT. This establishes that the substitution of a basic residue for an acidic residue at position 313 alleviates inter-helical charge repulsion between dimer partners and helps to stabilize the structural conformation.https://digitalcommons.odu.edu/gradposters2023_gradschool/1004/thumbnail.jp

UNCERTAINTY QUANTIFICATION ON A REAL CASE WITH TELEMAC-2D

Water Qualit

Orthoparamyxovirinae C Proteins Have a Common Origin and a Common Structural Organization

The protein C is a small viral protein encoded in an overlapping frame of the P gene in the subfamily Orthoparamyxovirinae. This protein, expressed by alternative translation initiation, is a virulence factor that regulates viral transcription, replication, and production of defective interfering RNA, interferes with the host-cell innate immunity systems and supports the assembly of viral particles and budding. We expressed and purified full-length and an N-terminally truncated C protein from Tupaia paramyxovirus (TupV) C protein (genus Narmovirus). We solved the crystal structure of the C-terminal part of TupV C protein at a resolution of 2.4 Å and found that it is structurally similar to Sendai virus C protein, suggesting that despite undetectable sequence conservation, these proteins are homologous. We characterized both truncated and full-length proteins by SEC-MALLS and SEC-SAXS and described their solution structures by ensemble models. We established a mini-replicon assay for the related Nipah virus (NiV) and showed that TupV C inhibited the expression of NiV minigenome in a concentration-dependent manner as efficiently as the NiV C protein. A previous study found that the Orthoparamyxovirinae C proteins form two clusters without detectable sequence similarity, raising the question of whether they were homologous or instead had originated independently. Since TupV C and SeV C are representatives of these two clusters, our discovery that they have a similar structure indicates that all Orthoparamyxovirine C proteins are homologous. Our results also imply that, strikingly, a STAT1-binding site is encoded by exactly the same RNA region of the P/C gene across Paramyxovirinae, but in different reading frames (P or C), depending on which cluster they belong to.French Agence Nationale de la RechercheFond de la Recherche Médicale (FRM)Grenoble Instruct-ERIC centerFRISBIUniversity Grenoble Alpes graduate school (Ecoles Universitaires de Recherche)Peer Reviewe

Seismic constraints on rotation of Sun-like star and mass of exoplanet

Rotation is thought to drive cyclic magnetic activity in the Sun and Sun-like stars. Stellar dynamos, however, are poorly understood owing to the scarcity of observations of rotation and magnetic fields in stars. Here, inferences are drawn on the internal rotation of a distant Sun-like star by studying its global modes of oscillation. We report asteroseismic constraints imposed on the rotation rate and the inclination of the spin axis of the Sun-like star HD 52265, a principal target observed by the CoRoT satellite that is known to host a planetary companion. These seismic inferences are remarkably consistent with an independent spectroscopic observation (rotational line broadening) and with the observed rotation period of star spots. Furthermore, asteroseismology constrains the mass of exoplanet HD 52265b. Under the standard assumption that the stellar spin axis and the axis of the planetary orbit coincide, the minimum spectroscopic mass of the planet can be converted into a true mass of 1.85 (+0.52,-0.42) M_Jupiter, which implies that it is a planet, not a brown dwarf.Comment: Published in Proceedings of the National Academy of Sciences (5 pages, 5 figures, 3 tables). Available at http://www.pnas.org/cgi/doi/10.1073/pnas.130329111

The DNA-binding domain of the Chd1 chromatin-remodelling enzyme contains SANT and SLIDE domains

The ATP-dependent chromatin-remodelling enzyme Chd1 is a 168-kDa protein consisting of a double chromodomain, Snf2-related ATPase domain, and a C-terminal DNA-binding domain. Here, we show the DNA-binding domain is required for Saccharomyces cerevisiae Chd1 to bind and remodel nucleosomes. The crystal structure of this domain reveals the presence of structural homology to SANT and SLIDE domains previously identified in ISWI remodelling enzymes. The presence of these domains in ISWI and Chd1 chromatin-remodelling enzymes may provide a means of efficiently harnessing the action of the Snf2-related ATPase domain for the purpose of nucleosome spacing and provide an explanation for partial redundancy between these proteins. Site directed mutagenesis was used to identify residues important for DNA binding and generate a model describing the interaction of this domain with DNA. Through inclusion of Chd1 sequences in homology searches SLIDE domains were identified in CHD6–9 proteins. Point mutations to conserved amino acids within the human CHD7 SLIDE domain have been identified in patients with CHARGE syndrome