Effects of (Small) Permanent Charge and Channel Geometry on Ionic Flows via Classical Poisson--Nernst--Planck Models

In this work, we examine effects of permanent charges on ionic flows through ion channels via a quasi-one-dimensional classical Poisson--Nernst--Planck (PNP) model. The geometry of the three-dimensional channel is presented in this model to a certain extent, which is crucial for the study in this paper. Two ion species, one positively charged and one negatively charged, are considered with a simple profile of permanent charges: zeros at the two end regions and a constant $Q_0$ over the middle region. The classical PNP model can be viewed as a boundary value problem (BVP) of a singularly perturbed system. The singular orbit of the BVP depends on $Q_0$ in a regular way. Assuming $|Q_0|$ is small, a regular perturbation analysis is carried out for the singular orbit. Our analysis indicates that effects of permanent charges depend on a rich interplay between boundary conditions and the channel geometry. Furthermore, interesting common features are revealed: for $Q_0=0$, only an average quantity of the channel geometry plays a role; however, for $Q_0\neq 0$, details of the channel geometry matter; in particular, to optimize effects of a permanent charge, the channel should have a short and narrow neck within which the permanent charge is confined. The latter is consistent with structures of typical ion channels

Unraveling Controversies Over Civic Honesty Measurement: An Extended Field Replication in China

Cohn et al. (2019) conducted a wallet drop experiment in 40 countries to measure civic honesty around the globe, which has received worldwide attention but also sparked controversies over using the email response rate as the sole metric of civic honesty. Relying on the lone measurement may overlook cultural differences in behaviors that demonstrate civic honesty. To investigate this issue, we conducted an extended replication study in China, utilizing email response and wallet recovery to assess civic honesty. We found a significantly higher level of civic honesty in China, as measured by the wallet recovery rate, than reported in the original study, while email response rates remained similar. To resolve the divergent results, we introduce a cultural dimension, individualism versus collectivism, to study civic honesty across diverse cultures. We hypothesize that cultural differences in individualism and collectivism could influence how individuals prioritize actions when handling a lost wallet, such as contacting the wallet owner or safeguarding the wallet. In reanalyzing Cohn et al.\u27s data, we found that email response rates were inversely related to collectivism indices at the country level. However, our replication study in China demonstrated that the likelihood of wallet recovery was positively correlated with collectivism indicators at the provincial level. Consequently, relying solely on email response rates to gauge civic honesty in cross-country comparisons may neglect the vital individualism versus collectivism dimension. Our study not only helps reconcile the controversy surrounding Cohn et al.\u27s influential field experiment but also furnishes a fresh cultural perspective to evaluate civic honesty

Di-(2-ethylhexyl) phthalate induces precocious puberty in adolescent female rats

Objective(s): Nowadays, Di-(2-ethylhexyl) phthalate (DEHP) is widely used in different kinds of commercial products as a plasticizer. Previous studies have revealed that exposures to DEHP could be associated with precocious puberty in teenagers, but the exact mechanism is yet to be known. Materials and Methods: In this study, 48 prepubertal Wistar female rats were randomly apportioned into 4 groups and orally treated with 0, 250, 500, and 1000 mg/kg/d DEHP from postnatal day 21 up to 4 weeks. Subsequently, we examined the indicators related to the initiation of sexual development. Results: DEHP was able to shorten the vaginal opening time and prolong the estrous cycles of female rats. IGF-1 expression was significantly upregulated by 1000 mg/kg/d DEHP in the hypothalamus, and the hypothalamic, as well as serum levels of GH, were also upregulated by DEHP. It also caused decrements in serum levels of FSH, LH, and T and the increment in level of progesterone. Meanwhile, DEHP was able to exert its effect on the mRNA and protein expression levels of Kiss-1, GPR54, and GnRH in the hypothalamus in pubertal female rats. Conclusion: These findings are revealing that DEHP exposure more likely causes imbalances of hypothalamus functioning in pubertal female rats and thus induces precautious puberty in these animals

Synthesis and Identification of a Novel Lead Targeting Survivin Dimerization for Proteasome-Dependent Degradation

Survivin, a homodimeric member of the Inhibitor of Apoptosis Protein (IAP) family, is required for cancer cell survival and overexpressed in almost all solid tumors. However, targeting survivin has been challenging due to its “undruggable” nature. Recently, we used a novel approach to target the dimerization interface and identified inhibitors of two scaffolds that can directly bind to and inhibit survivin dimerization. One of the scaffolds, represented by the compound LQZ-7, contains an undesirable labile hydrazone linker and a potentially nonfunctional furazanopyrazine ring that we attempted to eliminate in this study. We found one compound, 7I, that is more active than the parent compound, LQZ-7, and when given orally effectively inhibits xenograft tumor growth and induces survivin loss in tumors. These findings indicate that 7I with a stable linker and a quinoxaline ring can be used as a lead for further optimization of this novel class of survivin inhibitors

Outbred genome sequencing and CRISPR/Cas9 gene editing in butterflies

Butterflies are exceptionally diverse but their potential as an experimental system has been limited by the difficulty of deciphering heterozygous genomes and a lack of genetic manipulation technology. Here we use a hybrid assembly approach to construct high-quality reference genomes for Papilio xuthus (contig and scaffold N50: 492 kb, 3.4 Mb) and Papilio machaon (contig and scaffold N50: 81 kb, 1.15 Mb), highly heterozygous species that differ in host plant affiliations, and adult and larval colour patterns. Integrating comparative genomics and analyses of gene expression yields multiple insights into butterfly evolution, including potential roles of specific genes in recent diversification. To functionally test gene function, we develop an efficient (up to 92.5%) CRISPR/Cas9 gene editing method that yields obvious phenotypes with three genes, Abdominal-B, ebony and frizzled. Our results provide valuable genomic and technological resources for butterflies and unlock their potential as a genetic model system

Studies on Ionic Flows via Poisson–Nernst–Planck Systems with Bikerman’s Local Hard-Sphere Potentials under Relaxed Neutral Boundary Conditions

We examine the qualitative properties of ionic flows through ion channels via a quasi-one-dimensional Poisson–Nernst–Planck model under relaxed neutral boundary conditions. Bikerman’s local hard-sphere potential is included in the model to account for finite ion size effects. Our main interest is to examine the boundary layer effects (due to the relaxation of electroneutrality boundary conditions) on both individual fluxes and current–voltage relations systematically. Critical values of potentials are identified that play significant roles in studying internal dynamics of ionic flows. It turns out that the finite ion size can either enhance or reduce the ionic flow under different nonlinear interplays between the physical parameters in the system, particularly, boundary concentrations, boundary potentials, boundary layers, and finite ion sizes. Much more rich dynamics of ionic flows through membrane channels is observed