Human earwax consists of wet and dry types. Dry earwax is frequent in East Asians, whereas wet earwax is common in other populations. Here we show that a SNP, 538G --> A (rs17822931), in the ABCC11 gene is responsible for determination of earwax type. The AA genotype corresponds to dry earwax, and GA and GG to wet type. A 27-bp deletion in ABCC11 exon 29 was also found in a few individuals of Asian ancestry. A functional assay demonstrated that cells with allele A show a lower excretory activity for cGMP than those with allele G. The allele A frequency shows a north-south and east-west downward geographical gradient; worldwide, it is highest in Chinese and Koreans, and a common dry-type haplotype is retained among various ethnic populations. These suggest that the allele A arose in northeast Asia and thereafter spread through the world. The 538G --> A SNP is the first example of DNA polymorphism determining a visible genetic trait.

Production and consumption of nitrous oxide (N 2 O), methane (CH 4 ), and carbon dioxide (CO 2 ) are affected by complex interactions of temperature, moisture, and substrate supply, which are further complicated by spatial heterogeneity of the soil matrix. This microsite heterogeneity is often invoked to explain non-normal distributions of greenhouse gas (GHG) fluxes, also known as hot spots and hot moments.To advance numerical simulation of these belowground processes, we expanded the Dual Arrhenius and Michaelis-Menten model, to apply it consistently for all three GHGs with respect to the biophysical processes of production, consumption, and diffusion within the soil, including the contrasting effects of oxygen (O 2 ) as substrate or inhibitor for each process. High-frequency chamber-based measurements of all three GHGs at the Howland Forest (ME, USA) were used to parameterize the model using a multiple constraint approach. The area under a soil chamber is partitioned according to a bivariate log-normal probability distribution function (PDF) of carbon and water content across a range of microsites, which leads to a PDF of heterotrophic respiration and O 2 consumption among microsites. Linking microsite consumption of O 2 with a diffusion model generates a broad range of microsite concentrations of O 2 , which then determines the PDF of microsites that produce or consume CH 4 and N 2 O, such that a range of microsites occurs with both positive and negative signs for net CH 4 and N 2 O flux. Results demonstrate that it is numerically feasible for microsites of N 2 O reduction and CH 4 oxidation to co-occur under a single chamber, thus explaining occasional measurement of simultaneous uptake of both gases. Simultaneous simulation of all three GHGs in a parsimonious modeling framework is challenging, but it increases confidence that agreement between simulations and measurements is based on skillful numerical representation of processes across a heterogeneous environment.

Summary.  Background: In gene therapy, one of the most important issues is the choice of the vectors. pHrneo is a human‐derived vector previously constructed by our group, which can target a foreign gene into a human ribosomal DNA (hrDNA) locus. Methods and results: In this study, we inserted an expression cassette of reconstructive hFVIII (hFVIII‐BDDAK39) to pHrneo to construct a targeting vector: pHrneo‐BDDAK39. Through electroporation of pHrneo‐BDDAK39 into HL7702 cells (human hepatocyte), we identified the homologous recombinants using polymerase chain reaction, and tested the expression of hFVIII–BDDAK39 located at the hrDNA locus. The hFVIII‐BDDAK39 was successfully targeted into the hrDNA locus of HL7702 by pHrneo‐BDDAK39, and the efficiency of site‐specific integration was 1.1 × 10−5. The hFVIII‐BDDAK39 at the hrDNA locus of HL7702 was found to be able to express efficiently (4.3 ± 0.9 ng 10−6 cells 24 h−1). Conclusion: It has been indicated that the targeting vector pHrneo‐BDDAK39 can be used in gene therapy for hemophilia A.

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly transmitted by droplets and close contact, has caused a pandemic worldwide as of March 2020. According to the current case reports and cohort studies, the symptoms of pregnant women infected with SARS-CoV-2 were similar to normal adults and may cause a series of adverse consequences of pregnancy (placental abruption, fetal distress, epilepsy during pregnancy, etc.). However, whether SARS-CoV-2 can be transmitted to the fetus through the placental barrier is still a focus of debate. Methods In this study, in order to find out whether SARS-CoV-2 can infect fetus through the placental barrier, we performed qualitative detection of virus structural protein (spike protein and nucleoprotein) and targeted receptor protein Angiotensin Converting Enzyme 2 (ACE2), Basigin (CD147) and molecular chaperone GRP78 expression on the placental tissue of seven pregnant women diagnosed with COVID-19 through immunohistochemistry. Amniotic fluid, neonatal throat, anal swab and breastmilk samples were collected immediately in the operating room or delivery room for verification after delivery, which were all tested for SARS-CoV-2 by reverse transcriptionpolymerase chain reaction (RT-PCR). Results/discussion The result showed that CD147 was expressed on the basal side of the chorionic trophoblast cell membrane and ACE2 was expressed on the maternal side, while GRP78 was strongly expressed in the cell membrane and cytoplasm. The RT-PCR results of Amniotic fluid, neonatal throat, anal swab and breastmilk samples were all negative. On the basis of these findings, we speculated that it may be due to the placental barrier between mother and baby, for example, villous matrix and interstitial blood vessels have low expression of virus-related receptors (ACE2, CD147, GRP78), the probability of vertical transmission of SARS-CoV-2 through the placenta is low.

Gap junctions, consisting of connexins, allow the exchange of small molecules (<1 kD) between adjacent cells, thus providing a mechanism for synchronizing the responses of groups of cells to environmental stimuli. Connexin 31 is a member of the connexin family. Mutations on connexin 31 are associated with erythrokeratodermia variabilis, hearing impairment and peripheral neuropathy. However, the pathological mechanism for connexin 31 mutants in these diseases are still unknown. In this study, we analyzed the assembly, trafficking and metabolism of connexin 31 in HeLa cells stably expressing connexin 31. Calcein transfer assay showed that calcein transfer was inhibited when cells were treated with Brefeldin A or cytochalasin D, but not when treated with nocodazole or α-glycyrrhetinic acid, suggesting that Golgi apparatus and actin filaments, but not microtubules, are crucial to the trafficking and assembly of connexin 31, as well as the formation of gap junction intercellular communication by connexin 31. Additionally, α-glycyrrhetinic acid did not effectively inhibit gap junctional intercellular communication formed by connexin 31. Pulse-chase assay revealed that connexin 31 had a half-life of about 6 h. Moreover, Western blotting and fluorescent staining demonstrated that in HeLa cells stably expressing connexin 31, the amount of connexin 31 was significantly increased after these cells were treated with proteasomal or lysosomal inhibitors. These findings indicate that connexin 31 was rapidly renewed, and possibly degraded by both proteasomal and lysosomal pathways.