The ubiquitin E3 ligase SR1 modulates the submergence response by degrading phosphorylated WRKY33 in Arabidopsis.

Oxygen deprivation caused by flooding activates acclimation responses to stress and restricts plant growth. After experiencing flooding stress, plants must restore normal growth; however, which genes are dynamically and precisely controlled by flooding stress remains largely unknown. Here, we show that the Arabidopsis thaliana ubiquitin E3 ligase SUBMERGENCE RESISTANT1 (SR1) regulates the stability of the transcription factor WRKY33 to modulate the submergence response. SR1 physically interacts with WRKY33 in vivo and in vitro and controls its ubiquitination and proteasomal degradation. Both the sr1 mutant and WRKY33 overexpressors exhibited enhanced submergence tolerance and enhanced expression of hypoxia-responsive genes. Genetic experiments showed that WRKY33 functions downstream of SR1 during the submergence response. Submergence induced the phosphorylation of WRKY33, which enhanced the activation of RAP2.2, a positive regulator of hypoxia-response genes. Phosphorylated WRKY33 and RAP2.2 were degraded by SR1 and the N-degron pathway during reoxygenation, respectively. Taken together, our findings reveal that the on-and-off module SR1-WRKY33-RAP2.2 is connected to the well-known N-degron pathway to regulate acclimation to submergence in Arabidopsis. These two different but related modulation cascades precisely balance submergence acclimation with normal plant growth.

Phosphomolybdates for Dual-Mode Photoelectrochemical Sensing toward Trace Chromium(VI) and Tetracycline.

Highly sensitive photoelectrochemical (PEC) sensors for trace carcinogens, such as heavy metal chromium(VI) [Cr(VI)] and antibiotic tetracycline (TC) are crucial. Herein, by integration of photoactive and redox phosphomolybdates with conjugated organic components, types of dual-mode PEC sensors were synthesized for sensing trace Cr(VI) and TC pollutants, with formulas of (H2bimb)2[Co2(bimb)1.5][Co(H2O)4][Co(P4Mo6O31H6)2]·6H2O (1), (H2bib)2[Co(H2O)3][Co2(H2O)5][Co(P4Mo6O31H6)2]·9H2O (2), and (H2bib)6[Co(Hbib)2(H2O)5][Co(P4Mo6O31H7)2]2·15H2O (3), where bimb represents 1,4-bis(1-imidazolyl)benzene and bib is 4,4'-bis(imidazolyl)bibphenyl. Hybrid 1 consisted of a three-dimensional framework structure constructed by Co{P4Mo6}2 clusters and one-dimensional (1D) {Co-bimb} chains, hybrid 2 exhibited 1D Co ion-bridged Co{P4Mo6}2 chains hydrogen-bonding with [H2bib]2+ cations, and hybrid 3 showed a discrete hybrid structure built upon a Co{P4Mo6}2 cluster modified by the {Co-bib} unit. Hybrids 1-3 displayed wide spectral absorption and excellent electrochemical redox properties, enabling dual-mode PEC responses to Cr(VI) reduction and TC oxidation. For Cr(VI) detection, hybrids 1-3 exhibited high sensitivities of 364.40, 225.72, and 124.29 µA·µM-1 as well as "nM" level detection limits (LODs) of 4.9, 10.0, and 11.0 nM, respectively. For TC detection, the sensitivities of hybrids 1-3 were 494.72, 308.78, and 174.03 µA·µM-1 and the LODs were 5.2, 6.1, and 12.9 nM, respectively. This research offers significant insights into designing efficient PEC sensors for the detection of environmental pollutants.

Bridging Component Strategy in Phosphomolybdate-Based Sensors for Electrochemical Determination of Trace Cr(VI).

Rapid and sensitive electrochemical determination of trace carcinogenic Cr(VI) pollutants remains an urgent and important task, which requires the development of active sensing materials. Herein, four cases of reduced phosphomolybdates with formulas of the (H2bib)3[Zn(H2PO4)]2{Mn[P4Mo6O31H7]2}·6H2O (1), (H2bib)2[Na(H2O)]2[Mn(H2O)]2{Mn[P4Mo6O31H6]2}·5H2O (2), (H2bib)3[Mo2(µ2-O)2(H2O)4]2{Ni[P4Mo6O31H2]2}·4H2O (3), and (H2bib)2{Ni[P4Mo6O31H9]2}·9H2O (4) (bib = 4,4'-bis(1-imidazolyl)-biphenyl) were hydrothermally synthesized under the guidance of a bridging component strategy, which function as effective electrochemical sensors to detect trace Cr(VI). The difference of hybrids 1-4 is in the inorganic moiety, in which the reduced phosphomolybdates {M[P4MoV6O31]2} (M{P4Mo6}2) exhibited different arrangements bridged by different cationic components ({Zn(H2PO4)} subunit for 1, [Mn2(H2O)2]4+ dimer for 2, and [MoV2(µ2-O)2(H2O)4]6+ for 3). As a result, hybrids 1 and 3 display noticeable Cr(VI) detection activity with low detection limits of 14.3 nM (1.48 ppb) for 1 and 6.61 nM (0.69 ppb) for 3 and high sensitivities of 97.3 and 95.3 µA·mM-1, respectively, which are much beyond the World Health Organization's detection threshold (0.05 ppm) and superior to those of the contrast samples (inorganic Mn{P4Mo6}2 salt and hybrid 4), even the most reported noble-metal catalysts. This work supplies a prospective pathway to build effective electrochemical sensors based on phosphomolybdates for environmental pollutant treatment.

Backcrossing to different parents produced two distinct hybrid species.

Repeated homoploid hybrid speciation (HHS) events with the same parental species have rarely been reported. In this study, we used population transcriptome data to test paraphyly and HHS events in the conifer Picea brachytyla. Our analyses revealed non-sister relationships for two lineages of P. brachytyla, with the southern lineage being placed within the re-circumscribed P. likiangensis species complex (PLSC) and P. brachytyla sensu stricto (s.s.) consisted solely of the northern lineage, forming a distinct clade that is paratactic to both the PLSC and P. wilsonii. Our phylogenetic and coalescent analyses suggested that P. brachytyla s.s. arose from HHS between the ancestor of the PLSC before its diversification and P. wilsonii through an intermediate hybrid lineage at an early stage and backcrossing to the ancestral PLSC. Additionally, P. purpurea shares the same parents and an extinct lineage with P. brachytyla s.s. but backcrossing to the other parent, P. wilsonii at a later stage. We reveal the first case that backcrossing to different parents of the same extinct hybrid lineage produced two different hybrid species. Our results highlight the existence of more reticulate evolution during species diversification in the spruce genus and more complex homoploid hybrid events than previously identified.

The PalWRKY77 transcription factor negatively regulates salt tolerance and abscisic acid signaling in Populus.

High salinity, one of the most widespread abiotic stresses, inhibits photosynthesis, reduces vegetation growth, blocks respiration and disrupts metabolism in plants. In order to survive their long-term lifecycle, trees, such as Populus species, recruit the abscisic acid (ABA) signaling pathway to adapt to a saline environment. However, the molecular mechanism behind the ABA-mediated salt stress response in woody plants remains elusive. We have isolated a WRKY transcription factor gene, PalWRKY77, from Populus alba var. pyramidalis (poplar), the expression of which is repressed by salt stress. PalWRKY77 decreases salt tolerance in poplar. Furthermore, PalWRKY77 negatively regulated ABA-responsive genes and relieved ABA-mediated growth inhibition, indicating that PalWRKY77 is a repressor of the ABA response. In vivo and in vitro assays revealed that PalWRKY77 targets the ABA- and salt-induced PalNAC002 and PalRD26 genes by binding to the W-boxes in their promoters. In addition, overexpression of both PalNAC002 and PalRD26 could elevate salt tolerance in transgenic poplars. These findings reveal a novel negative regulation mechanism for the ABA signaling pathway mediated by PalWRKY77 that results in more sensitivity to salt stress in poplar. This deepens our understanding of the complex responses of woody species to salt stress.

LncRNA PITPNA-AS1/miR-223-3p/PTN axis regulates malignant progression and stemness in lung squamous cell carcinoma.

BACKGROUND: Long noncoding RNAs (lncRNAs) are a kind of molecule that cannot code proteins, and their expression is dysregulated in diversified cancers. LncRNA PITPNA-AS1 has been shown to act as a tumor promoter in a variety of malignancies, but its function and regulatory mechanisms in lung squamous cell carcinoma (LUSC) are yet unknown. METHODS: The mRNA and protein expression of genes were examined by RT-qPCR, western blot, and IHC assay. The cell proliferation, migration, invasion, and stemness were detected through CCK-8, colony formation, Transwell and spheroid formation assays. The CD44+ and CD166+ -positive cells were detected through flow cytometry. The binding ability among genes through luciferase reporter and RNA pull-down assays. The tumor growth was detected through in vivo nude mice assay. RESULTS: The lncRNA PITPNA-AS1 had increased expression in LUSC and was linked to a poor prognosis. In LUSC, PITPNA-AS1 also enhanced cell proliferation, migration, invasion, and stemness. This mechanistic investigation showed that PITPNA-AS1 absorbed miR-223-3p and that miR-223-3p targeted PTN. MiR-223-3p inhibition or PTN overexpression might reverse the inhibitory effects of PITPNA-AS1 suppression on LUSC progression, as demonstrated by rescue experiments. In addition, the PITPNA-AS1/miR-223-3p/PTN axis accelerated tumor development in vivo. CONCLUSIONS: It is the first time we investigated the potential role and ceRNA regulatory mechanism of PITPNA-AS1 in LUSC. The data disclosed that PITPNA-AS1 upregulated PTN through sponging miR-223-3p to enhance the onset and progression of LUSC. These findings suggested the ceRNA axis may serve as a promising therapeutic biomarker for LUSC patients.

CHYR1 ubiquitinates the phosphorylated WRKY70 for degradation to balance immunity in Arabidopsis thaliana.

It is critically important for plants to control the trade-off between normal growth and pathogen immunity. However, the underlying molecular mechanism remains largely unknown. Here we report such a mechanism controlled by WRKY70 and its partner CHYR1 in Arabidopsis. We found that both levels of the WRKY70 target gene SARD1 and the phosphorylated forms of WRKY70 were increased in WRKY70OE plants upon Pst DC3000 infection. Mechanistically, phosphorylation of WRKY70 at Thr22 and Ser34 occurs, which then activates SARD1 expression through binding to a WT box. Phosphorylated WRKY70 is degraded by 26S proteasome via CHYR1 when resuming normal growth after infection. In addition, nonphosphorylated WRKY70 represses SARD1 expression by binding to both W (inhibitory activity site) and WT (active activity site) boxes. The binding of WRKY70 to alternative cis-elements of SARD1 through a phosphorylation-mediated switch controlled by CHYR1 contributes to modulating the balance between immunity and growth.

WRKY33 interacts with WRKY12 protein to up-regulate RAP2.2 during submergence induced hypoxia response in Arabidopsis thaliana.

Tolerance of hypoxia is essential for most plants, but the underlying mechanisms are largely unknown. Here we show that adaptation to submergence induced hypoxia in Arabidopsis involves up-regulation of RAP2.2 through interactive action of WRKY33 and WRKY12. WRKY33- or WRKY12-overexpressing plants showed enhanced resistance to hypoxia. Y2H, BiFC, Co-IP and pull-down experiments confirmed the interaction of WRKY33 with WRKY12. Genetic experiments showed that RAP2.2 acts downstream of WRKY33/WRKY12. WRKY33 and WRKY12 can bind to and activate RAP2.2 individually. Genetic and molecular experiments demonstrate that the two WRKYs can synergistically enhance activation towards RAP2.2 to increase hypoxia tolerance. WRKY33 expression is increased in RAP2.2-overexpressing plants, indicating a feedback regulation by RAP2.2 during submergence process, which was corroborated by EMSA, ChIP, dual-LUC and genetic experiments. Our results show that a regulatory cascade module involving WRKY33, WRKY12 and RAP2.2 plays a key role in submergence induced hypoxia response of Arabidopsis and illuminate functions of WRKYs in hypoxia tolerance.

Efficacy of hyperbaric oxygen combined with escitalopram in depression and its effect on cognitive function.

OBJECTIVE: To investigate the efficacy of hyperbaric oxygen (HBO) combined with escitalopram in patients with depression and its effect on cognitive function. METHODS: From 2016 to 2018, seventy patients with depression aged 18-65 years treated in Affiliated Hospital of Hebei University were selected. Seventy patients with depression meeting the diagnostic criteria of ICD-10 were selected and randomly divided into control group and observation group using a random number table, with 35 patients in each group. The control group was treated with escitalopram, while the observation group was additionally treated with HBO on this basis. The patients were assessed using the Hamilton Depression Scale (HAMD) and Montreal Cognitive Assessment Scale (MoCA) before treatment and two, four and six weeks after treatment. RESULTS: Two weeks after treatment, HAMD score showed a statistically significant difference between the two groups (P < 0.05). No statistically significant differences were found in HAMD score between the two groups four and six weeks after treatment (P > 0.05). Four and six weeks after treatment, MoCA score presented statistically significant differences between the two groups (P < 0.05). CONCLUSION: Escitalopram combined with HBO in the treatment of depression presents rapid efficacy and a certain effect in improving cognitive function.

Hepatitis E virus and blood transfusion safety.

While the majority of worldwide hepatitis E viral (HEV) infections that occur in people are from contaminated water or food sources, there has also been a steadily rising number of reported cases of transfusion-transmitted HEV (TT-HEV) in blood donation recipients. For most, HEV infection is acute, self-limiting and asymptomatic. However, patients that are immunocompromised, especially transplant patients, are at much higher risk for developing chronic infections, which can progress to cirrhosis and liver failure, along with overall increased mortality. Because of the rising trend of HEV serological prevalence among the global population, and the fact that TT-HEV infection can cause serious clinical consequences among those patients most at need for blood donation, the need for screening for TT-HEV has been gaining in prominence as an important public health concern for both developing and developed countries. In the review, we summarise evidence for and notable cases of TT-HEV infections, the various aspects of HEV screening protocols and recent trends in the implementation of TT-HEV broad-based blood screening programmes.

Engineering and manipulation of a mevalonate pathway in Escherichia coli for isoprene production.

Isoprene is a useful phytochemical with high commercial values in many industrial applications including synthetic rubber, elastomers, isoprenoid medicines, and fossil fuel. Currently, isoprene is on large scale produced from petrochemical sources. An efficient biological process for isoprene production utilizing renewable feedstocks would be an important direction of research due to the fossil raw material depletion and air pollution. In this study, we introduced the mevalonate (MVA) pathway genes/acetoacetyl-coenzyme A thiolase (mvaE) and MVA synthase (mvaS) from Enterococcus faecalis (E. faecalis); MVA kinase (mvk) derived from Methanosarcina mazei (M. mazei); and phosphomevalonate kinase (pmk), diphosphomevalonate decarboxylase (mvaD), and isopentenyl diphosphate isomerase (idi) from Streptococcus pneumoniae (S. pneumoniae) to accelerate dimethylallyl diphosphate (DMAPP) accumulation in Escherichia coli (E. coli). Together with a codon-optimized isoprene synthase (ispS) from Populus alba (P. alba), E. coli strain succeeded in formation of isoprene. We then manipulated the heterologous MVA pathway for high-level production of isoprene, by controlling the gene expression levels of the MVA pathway genes. We engineered four E. coli strains which showed different gene expression levels and different isoprene productivities, and we also characterized them with quantitative real-time PCR and metabolite analysis. To further improve the isoprene titers and release the toxicity to cells, we developed the extraction fermentation by adding dodecane in cultures. Finally, strain BL2T7P1TrcP harboring balanced gene expression system produced 587 ± 47 mg/L isoprene, with a 5.2-fold titer improvement in comparison with strain BL7CT7P. This work indicated that a balanced metabolic flux played a significant role to improve the isoprene production via MVA pathway.

A novel DMAPP-responding genetic circuit sensor for high-throughput screening and evolving isoprene synthase.

High-throughput screening is a popular tool for collating biological data which would otherwise require the use of excessive resources. In this study, an artificial genetic circuit sensor responding to dimethylallyl diphosphate (DMAPP) was constructed based on a modified L-arabinose operon for high-throughput screening and isoprene synthase (ispS) evolution in Escherichia coli (E. coli). As a first step, the DNA sequence of the L-arabinose ligand-binding domain (LBD) was replaced with an ispS gene to enable the AraC operon responding to DMAPP, which is the substrate of the IspS enzyme. Then, an enhanced GFP (eGFP) was also introduced as a reporter for pBAD promoter. The expression level of the reporter was monitored using either of the two tools: flow cytometer (FCM) and microplate reader. Sequentially, we observed that a high DMAPP concentration led to low eGFP fluorescence, and the overexpression of ispS gene, which consumes DMAPP, resulted in a high eGFP expression. These results demonstrated that the artificial genetic circuit sensor responded directly to the intracellular concentration of DMAPP, and the expression of IspS enzyme could be positively correlated to the expression level of eGFP. Finally, we identified two IspS mutants with different activities from an ispS gene library and further validated the screening method.

Advances in terahertz metasurface graphene for biosensing and application.

Based on the extraordinary electromagnetic properties of terahertz waves, such as broadband, low energy, high permeability, and biometric fingerprint spectra, terahertz sensors show great application prospects in the biochemical field. However, the sensitivity of terahertz sensing technology is increasingly required by modern sensing demands. With the development of terahertz technology and functional materials, graphene-based terahertz metasurface sensors with the advantages of high sensitivity, fingerprint identification, nondestructive and anti-interference are gradually gaining attention. In addition to providing ideas for terahertz biosensors, these devices have attracted in-depth research and development by scientists. An overview of graphene-based terahertz metasurfaces and their applications in the detection of biochemical molecules is presented. This includes sensor mechanism research, graphene metasurface index evaluation, protein and nucleic acid sensors, and other chemical molecule sensing. A comparative analysis of graphene, nanomaterials, silicon, and metals to develop material-integrated metasurfaces. Furthermore, a brief summary of the main performance results of this class of devices is presented, along with suggestions for improvements to the existing shortcoming.

Characterization of a new male sterility-related gene Camf1 in Capsicum annum L.

For the sake of screening novel genes related to the male sterility in chili pepper for studying the molecular mechanism of plant male sterility, the gene differential expression analysis was performed by cDNA-amplified fragment length polymorphism (cDNA-AFLP) in the genic male sterile-fertile line 114AB of Capsicum annum L., and a variety of differentially expressed cDNA fragments were detected in fertile or sterility material. Camf1, a transcript-derived fragment (TDF) accumulated in fertile line flower buds was further investigated. The Camf1 has 1,854 bp in length with no introns containing a 1,707-bp open reading frame (ORF). The deduced amino acid sequence of Camf1 shares higher similarity to some members from a glyoxal oxidase-related protein family, and has a glyoxal oxidase conserved domain at the N-terminus and a domain of unknown function (DUF1929) at C-terminal end. Expression analysis showed that Camf1 expressed only in stage 3-7 flower buds of male fertile of C. annum L. 114AB, and no detection in all organs of male sterility. The peak of expression level of Camf1 appeared at stage 4 flower buds of fertile line. Furthermore, expression analysis of different organs revealed that Camf1 expressed only in anthers of male fertile material and there were no expression in sepals, petals, pistils, roots, stems, leaves and open flowers. These results suggested that Camf1 was an anther-specific gene and might be essential for the fertility of C. annum L.

Removal of bisphenol A from aqueous solution by a dodecylsulfate ion-intercalated hydrotalcite-like compound.

A Mg-Al hydrotalcite-like compound (HTlc) and a dodecylsufate ion-intercalated Mg-Al HTlc (MHTlc) were prepared. The effects of temperature, ionic strength, and initial pH on the adsorptions ofbisphenol A (BPA) on both HTlc and MHTlc were studied in detail. The adsorption capacity of the pristine HTlc for BPA was low, and the adsorption was due to the substitution of surface anions within the pristine HTlc by the hydroxybenzene anion that was dissociated from BPA. The adsorption capacity for BPA increased notably with modification. The high adsorption capacity of MHTlc for BPA was mainly due to the dissolution of BPA molecules into the hydrophobic organic phase formed in the interlayers of MHTlc. The adsorption capacity of MHTlc for BPA decreased with increasing temperature and initial pH, but increased when increasing the ionic strength.

Prenatal diagnosis of de novo isochromosome 4p with an unbalanced t(4;9) translocation in a fetus with congenital anomalies: A case report and literature review.

OBJECTIVE: We present the first case of prenatally diagnosed isochromosome 4p with whole 4q arm translocating to chromosome 9p23 and review the literature. CASE REPORT: A 26-year-old woman underwent amniocentesis at 25 weeks of gestation because of an abnormal ultrasound examination. Routine chromosome analysis on cultured amniocytes showed a karyotype of 46,XX, ?idic(4)(q11),der(9)t(4;9)(q11;p23). Single nucleotide polymorphism (SNP) array analysis on uncultured amniocytes detected two copy number variations (CNVs): arr [GRCh37] 4p16.3p11(68345-49089361) × 3; arr [GRCh37] 9p24.3p23(208454-10039391) × 1. The karyotypes of the parents were normal, indicating that the chromosomal rearrangement was de novo. According to the fetal-parent trios SNP analysis, both the abnormal chromosomes were originated from the father. The pregnancy was terminated at 30 weeks of gestation, and a malformed fetus was delivered with dysmorphic craniofacial, short neck, wide-spaced nipples and rocker-bottom feet. CONCLUSION: The combined application of traditional cytogenetic technology and molecular diagnosis technology in prenatal diagnosis helps identify genetic components and the origin of isochromosome, which enable clinicians to precisely predict the fetal prognosis and provide accurate genetic counselling and fertility guidance.

Incidence rate of schizophrenia after the Tangshan earthquake in China: a 44-year retrospective birth cohort study.

Preliminary evidence indicates that natural disasters are associated with an increased risk for schizophrenia. With few longitudinal studies on earthquakes, this retrospective cohort study examined exposure to the 1976 Tangshan earthquake and the subsequent risk of schizophrenia. Population counts and visits to all nine psychiatric hospitals in Tangshan city were collected. We created three cohort groups by earthquake exposure: infant (August 1972 to July 1976 births), fetal (August 1976 to May 1977 births), and unexposed (June 1977 to May 1981 births). The cumulative incidence of schizophrenia in each cohort was calculated by dividing the number of schizophrenia patients by total births in the corresponding period. Altogether, 6424 schizophrenia patients were identified, with 2786 in the infant group, 663 in the fetal group, and 2975 in the unexposed group. The crude cumulative incidence of schizophrenia in the infant, fetal and unexposed groups were 7.64 (95% confidence interval [CI] = 7.36-7.92), 9.07 (95% CI = 8.38-9.76), and 7.40 (95% CI = 7.13-7.66) per thousand population respectively. Adjusted for mortality, the corresponding figures were 7.73 (95% CI = 7.44-8.01), 9.30 (95% CI = 8.60-10.01) and 7.44 (95% CI = 7.18-7.71) per thousand population respectively. The mortality-adjusted risk ratio (aRR) was 1.25 (95% CI = 1.15-1.36) between fetal and unexposed groups (χ2 = 27.31, P < 0.001). Males exposed as infants did not differ from the unexposed in cumulative schizophrenia incidence. People with fetal exposure to the 1976 earthquake had 25% higher risk of developing schizophrenia compared to unexposed counterparts.

Molecular signatures of parallel adaptive divergence causing reproductive isolation and speciation across two genera.

Parallel evolution of reproductive isolation (PERI) provides strong evidence for natural selection playing a fundamental role in the origin of species. However, PERI has been rarely demonstrated for well established species drawn from different genera. In particular, parallel molecular signatures for the same genes in response to similar habitat divergence in such different lineages is lacking. Here, based on whole-genome sequencing data, we first explore the speciation process in two sister species of Carpinus (Betulaceae) in response to divergence for temperature and soil-iron concentration in habitats they occupy in northern and southwestern China, respectively. We then determine whether parallel molecular mutations occur during speciation in this pair of species and also in another sister-species pair of the related genus, Ostryopsis, which occupy similarly divergent habitats in China. We show that gene flow occurred during the origin of both pairs of sister species since approximately 9.8 or approximately 2 million years ago, implying strong natural selection during divergence. Also, in both species pairs we detected concurrent positive selection in a gene (LHY) for flowering time and in two paralogous genes (FRO4 and FRO7) of a gene family known to be important for iron tolerance. These changes were in addition to changes in other major genes related to these two traits. The different alleles of these particular candidate genes possessed by the sister species of Carpinus were functionally tested and indicated likely to alter flowering time and iron tolerance as previously demonstrated in the pair of Ostryopsis sister species. Allelic changes in these genes may have effectively resulted in high levels of prezygotic reproductive isolation to evolve between sister species of each pair. Our results show that PERI can occur in different genera at different timescales and involve similar signatures of molecular evolution at genes or paralogues of the same gene family, causing reproductive isolation as a consequence of adaptation to similarly divergent habitats.

Alkylating antitumor drug mechlorethamine conceals a structured PrP domain and inhibits in vitro prion amplification.

Prion diseases are a group of incurable transmissible neurodegenerative disorders. The key molecular event in the pathogenesis of prion diseases is the conversion of the cellular prion protein (PrP(C)) into its pathological isoform (PrP(Sc)), accompanied by a conformational transition of α-helix into ß-sheet structure involving the structured α-helix 1 domain from residues 144-154 of the protein (PrP144-154). Blocking the accessibility of PrP144-152 with anti-PrP antibody 6H4 was found to prevent PrP conversion and even to cure prion infection in cell models ( Enari et al. 2001 ). Previously, Yuan et al. (2005 ) demonstrated that the reduction and alkylation of PrP induced concealment of the 6H4 epitope. This study examined the ability of mechlorethamine (MCT), an alkylating antitumor drug, to conceal the 6H4 epitope and block PrP conversion in the presence of a reducing reagent. Mechlorethamine treatment significantly decreased in vitro amplification of PrP(Sc) in the highly efficient protein misfolding cyclic amplification system. Our findings suggest that MCT may serve as a potential therapeutic agent for prion diseases.

Familial Aggregation and Heritability of Myopia: A Local Population Survey in Shanxi, China.

PURPOSE: To further determine the roles of environmental and genetic factors in the development of myopia, a comprehensive survey was performed. The guidance for myopia-susceptible people is established which might help prevent or delay the onset and development of myopia. METHODS: 1,852 students were recruited using the multistage sampling approach from the Gaoping county in Shanxi. The refractive status of students was examined using an autorefractometer, and the refractive status of students' first-degree relatives was collected using a well-designed questionnaire. Family aggregation of myopia was analyzed according to the myopic status of the students (nonmyopic or myopic group). The prevalence and heritability of myopia in students and their first-degree relatives were further explored by subdividing into mild, moderate, and high myopia groups. Significance analysis among each group was performed by the χ 2 test using SPSS 25.0 software. Falconer's method was used to calculate the inheritability of myopia. RESULTS: A total of 1,852 subjects were recruited in this study, and 1,813 subjects were finally included. The family aggregation of myopia in the myopic student group (34.7%) was significantly higher than that in the nonmyopic group (8.5%). The prevalence of mild, moderate, and high myopia in children (students and siblings) was higher than that in their parents. The rate of high myopia (6.33%) was significantly higher among students with one or both myopic parents than those without myopic parents (3.85%). The heritability of mild, moderate, and high myopia among parents-offspring was 3.72%, 20.47%, and 48.00%, respectively. The heritability of mild, moderate, and high myopia among siblings was 17.50%, 86.09%, and 78.75%, which is significantly higher than that among parents-offspring. In addition to genetic factors, extensive near-work time, higher education pressure, and minimal outdoor activities contribute significantly to mild and moderate myopia. CONCLUSIONS: Myopia is of high risk due to familial aggregation. Students with a family history of myopia are more likely to have high myopia than those without family history. The occurrence and development of high myopia are affected by both the genetic and environmental factors, which could either weaken or strengthen myopia. Therefore, students with a family history of myopia should pay close attention to their eye health to avoid the occurrence of myopia and the deepening of diopter, which may lead to high myopia and its related complications.