Ordered Nanoscale Heterojunction Architecture for Enhanced Solution‐Based CuInGaS2 Thin Film Solar Cell Performance

Nanopatterned CuInGaS₂ (CIGS) thin films synthesized by a sol‐gel‐based solution method and a nanoimprint lithography technique to achieve simultaneous photonic and electrical enhancements in thin film solar cell applications are demonstrated. The interdigitated CIGS nanopatterns in adjacent CdS layer form an ordered nanoscale heterojunction of optical contrast to create a light trapping architecture. This architecture concomitantly leads to increased junction area between the p‐CIGS/n‐CdS interface, and thereby influences effective charge transport. The electron beam induced current and capacitance–voltage characterization further supports the large carrier collection area and small depletion region of the nanopatterned CIGS solar cell devices. This strategic geometry affords localization of incident light inside and between the nanopatterns, where created excitons are easily dissociated, and it leads to the enhanced current generation of absorbed light. Ultimately, this approach improves the efficiency of the nanopatterned CIGS solar cell by 55% compared to its planar counterpart, and offers the possibility of simultaneous management for absorption and charge transport through a nanopatterning process.     

Generation of Chinese cabbage resistant to bacterial soft rot by heterologous expression of <Emphasis Type="Italic">Arabidopsis WRKY75</Emphasis>

Soft rot caused by Pectobacterium carotovorum subsp. carotovorum (Pcc) is a serious disease in Chinese cabbage (Brassica rapa L. subsp. pekinensis). To reduce the severity of soft rot symptoms in Chinese cabbage, Arabidopsis AtWRKY75 was introduced into Chinese cabbage by Agrobacterium-mediated transformation, which was previously reported to reduce susceptibility to Pcc infection in Arabidopsis. Three independent Chinese cabbage transgenic lines carrying AtWRKY75 were obtained. The growth phenotypes of AtWRKY75 overexpression (OE) lines were normal. Bacterial soft rot symptoms and Pcc growth were reduced in AtWRKY75-OE Chinese cabbage lines compared with WT plants. In contrast, overexpression of AtWRKY75 had no effect on infection with a hemibiotrophic pathogen, Xanthomonas campestris pv. campestris (Xcc) causing black rot disease. These results are consistent with those observed in the transgenic Arabidopsis. We found that AtWRKY75 activated a subset of Chinese cabbage genes related to defense against Pcc infection, such as Meri15B, BrPR4, and BrPDF1.2 (but not BrPGIP2). Moreover, overexpression of AtWRKY75 caused H₂O₂ production and activation of H₂O₂ scavenge enzyme genes, suggesting that H₂O₂ played a role in AtWRKY75-mediated resistance to Pcc. Together, these results demonstrated that AtWRKY75 decreased the severity of Pcc-caused bacterial soft rot and activated a subset of Pcc infection defense-related genes in Chinese cabbage similar to in Arabidopsis. It is suggested that AtWRKY75 is a candidate gene for use in crop improvement, because it results in reduced severity of disease symptoms without concurrent growth abnormalities.     

The ULK1 complex mediates MTORC1 signaling to the autophagy initiation machinery via binding and phosphorylating ATG14

ULK1 (unc-51 like autophagy activating kinase 1), the key mediator of MTORC1 signaling to autophagy, regulates early stages of autophagosome formation in response to starvation or MTORC1 inhibition. How ULK1 regulates the autophagy induction process remains elusive. Here, we identify that ATG13, a binding partner of ULK1, mediates interaction of ULK1 with the ATG14-containing PIK3C3/VPS34 complex, the key machinery for initiation of autophagosome formation. The interaction enables ULK1 to phosphorylate ATG14 in a manner dependent upon autophagy inducing conditions, such as nutrient starvation or MTORC1 inhibition. The ATG14 phosphorylation mimics nutrient deprivation through stimulating the kinase activity of the class III phosphatidylinositol 3-kinase (PtdIns3K) complex and facilitates phagophore and autophagosome formation. By monitoring the ATG14 phosphorylation, we determined that the ULK1 activity requires BECN1/Beclin 1 but not the phosphatidylethanolamine (PE)-conjugation machinery and the PIK3C3 kinase activity. Monitoring the phosphorylation also allowed us to identify that ATG9A is required to suppress the ULK1 activity under nutrient-enriched conditions. Furthermore, we determined that ATG14 phosphorylation depends on ULK1 and dietary conditions in vivo. These results define a key molecular event for the starvation-induced activation of the ATG14-containing PtdIns3K complex by ULK1, and demonstrate hierarchical relations between the ULK1 activation and other autophagy proteins involved in phagophore formation.     

Hand,Foot, and Mouth Disease in China: Modeling Epidemic Dynamics of Enterovirus Serotypes and Implications for Vaccination

Background

Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by serotypes of the Enterovirus A species in the genus Enterovirus of the Picornaviridae family. The disease has had a substantial burden throughout East and Southeast Asia over the past 15 y. China reported 9 million cases of HFMD between 2008 and 2013, with the two serotypes Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) being responsible for the majority of these cases. Three recent phase 3 clinical trials showed that inactivated monovalent EV-A71 vaccines manufactured in China were highly efficacious against HFMD associated with EV-A71, but offered no protection against HFMD caused by CV-A16. To better inform vaccination policy, we used mathematical models to evaluate the effect of prospective vaccination against EV-A71-associated HFMD and the potential risk of serotype replacement by CV-A16. We also extended the model to address the co-circulation, and implications for vaccination, of additional non-EV-A71, non-CV-A16 serotypes of enterovirus.

Methods and Findings

Weekly reports of HFMD incidence from 31 provinces in Mainland China from 1 January 2009 to 31 December 2013 were used to fit multi-serotype time series susceptible–infected–recovered (TSIR) epidemic models. We obtained good model fit for the two-serotype TSIR with cross-protection, capturing the seasonality and geographic heterogeneity of province-level transmission, with strong correlation between the observed and simulated epidemic series. The national estimate of the basic reproduction number, R ₀, weighted by provincial population size, was 26.63 for EV-A71 (interquartile range [IQR]: 23.14, 30.40) and 27.13 for CV-A16 (IQR: 23.15, 31.34), with considerable variation between provinces (however, predictions about the overall impact of vaccination were robust to this variation). EV-A71 incidence was projected to decrease monotonically with higher coverage rates of EV-A71 vaccination. Across provinces, CV-A16 incidence in the post-EV-A71-vaccination period remained either comparable to or only slightly increased from levels prior to vaccination. The duration and strength of cross-protection following infection with EV-A71 or CV-A16 was estimated to be 9.95 wk (95% confidence interval [CI]: 3.31, 23.40) in 68% of the population (95% CI: 37%, 96%). Our predictions are limited by the necessarily short and under-sampled time series and the possible circulation of unidentified serotypes, but, nonetheless, sensitivity analyses indicate that our results are robust in predicting that the vaccine should drastically reduce incidence of EV-A71 without a substantial competitive release of CV-A16.

Conclusions

The ability of our models to capture the observed epidemic cycles suggests that herd immunity is driving the epidemic dynamics caused by the multiple serotypes of enterovirus. Our results predict that the EV-A71 and CV-A16 serotypes provide a temporary immunizing effect against each other. Achieving high coverage rates of EV-A71 vaccination would be necessary to eliminate the ongoing transmission of EV-A71, but serotype replacement by CV-A16 following EV-A71 vaccination is likely to be transient and minor compared to the corresponding reduction in the burden of EV-A71-associated HFMD. Therefore, a mass EV-A71 vaccination program of infants and young children should provide significant benefits in terms of a reduction in overall HFMD burden.     

A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy

Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of peripheral neuropathies with diverse genetic causes. In this study, we identified p.I43N mutation in PMP2 from a family exhibiting autosomal dominant demyelinating CMT neuropathy by whole exome sequencing and characterized the clinical features. The age at onset was the first to second decades and muscle atrophy started in the distal portion of the leg. Predominant fatty replacement in the anterior and lateral compartment was similar to that in CMT1A caused by PMP22 duplication. Sural nerve biopsy showed onion bulbs and degenerating fibers with various myelin abnormalities. The relevance of PMP2 mutation as a genetic cause of dominant CMT1 was assessed using transgenic mouse models. Transgenic mice expressing wild type or mutant (p.I43N) PMP2 exhibited abnormal motor function. Electrophysiological data revealed that both mice had reduced motor nerve conduction velocities (MNCV). Electron microscopy revealed that demyelinating fibers and internodal lengths were shortened in both transgenic mice. These data imply that overexpression of wild type as well as mutant PMP2 also causes the CMT1 phenotype, which has been documented in the PMP22. This report might expand the genetic and clinical features of CMT and a further mechanism study will enhance our understanding of PMP2-associated peripheral neuropathy.     

Biomedical therapy using synthetic WKYMVm hexapeptide

WKYMVm hexapeptide has been identified as a strong FPR2 agonist through a library screening of synthetic peptides. The FPR2 has been reported to play a crucial role in inflammation and angiogenic responses via stimulation of chemotaxis, migration, cell proliferation, wound healing and vessel growth. Recently, the therapeutic effects of WKYMVm have been reported in various disease models. In cutaneous wound model in diabetic mice, WKYMVm facilitated wound healing processes by stimulating the formation of capillary and arteriole and re-epithelialization. In coronary artery stenosis model, WKYMVm coating on stent promoted re-endothelialization and lowered restenosis rate. In hindlimb ischemia mouse model, intramuscular injection of WKYMVm promoted homing of exogenously transplanted endothelial colony-forming cells and neovascularization, resulting in salvaging hindlimb. Furthermore, a single injection of WKYMVm encapsulated in poly (lactide-co-glycolide) microspheres was demonstrated to be as efficient as multiple injections of WKYMVm in restoring blood flow in hindlimb ischemia model. These observations may open up promising biomedical applications of WKYMVm for tissue repairs and regenerations.     

Production of Mucosally Transmissible SHIV Challenge Stocks from HIV-1 Circulating Recombinant Form 01_AE env Sequences

Simian-human immunodeficiency virus (SHIV) challenge stocks are critical for preclinical testing of vaccines, antibodies, and other interventions aimed to prevent HIV-1. A major unmet need for the field has been the lack of a SHIV challenge stock expressing circulating recombinant form 01_AE (CRF01_AE) env sequences. We therefore sought to develop mucosally transmissible SHIV challenge stocks containing HIV-1 CRF01_AE env derived from acutely HIV-1 infected individuals from Thailand. SHIV-AE6, SHIV-AE6RM, and SHIV-AE16 contained env sequences that were >99% identical to the original HIV-1 isolate and did not require in vivo passaging. These viruses exhibited CCR5 tropism and displayed a tier 2 neutralization phenotype. These challenge stocks efficiently infected rhesus monkeys by the intrarectal route, replicated to high levels during acute infection, and established chronic viremia in a subset of animals. SHIV-AE16 was titrated for use in single, high dose as well as repetitive, low dose intrarectal challenge studies. These SHIV challenge stocks should facilitate the preclinical evaluation of vaccines, monoclonal antibodies, and other interventions targeted at preventing HIV-1 CRF01_AE infection.     

Computational investigation on MB<Subscript><Emphasis Type="Italic">n</Emphasis></Subscript> (M = Li-Cs,Be-Ba,Sc-La and Ti; <Emphasis Type="Italic">n</Emphasis> = 28 and 38)

Differing from the weakly antiaromatic B₈₀ buckyball, the medium-sized C ₁–B₂₈ and D _2h –B₃₈, as well as their mono- to tetra-anions, are highly aromatic, as indicated by the negative nucleus-independent chemical shifts (NICSs) at their cage centers. The interior cavities and high aromaticity of the B₂₈ and B₃₈ cages render them very promising hosts to accommodate diverse metal atoms. Accordingly, we carried out systematic density functional theory (DFT) computations on the structures, stabilities and electronic properties of metalloborofullerenes MB _n (M?=?Li, Na, K, Rb, Cs, Be, Mg, Ca, Sr, Ba, Sc, Y, La and Ti; n?=?28 and 38). Among them, besides the recently reported M@B₃₈(M?=?Sc, Y and Ti) [Lu et al. (2015) Phys Chem Chem Phys 17:20897–20902], Ti@B₂₈ and M@B₃₈ (M?=?Ca and La) also favor endohedral structures with large binding energies, and are suggested promising targets for experimental applications. Note that Ti@B₂₈ is the first endohedral derivative based on the new B₂₈ fullerene, and La@B₃₈ features the largest metal size inside a B₃₈ cage thus far. These endohedral derivatives, as exemplified by Ca@B₃₈, may exhibit σ and π double aromaticity over the whole cage surface, indicating their considerable stability. In contrast, the other metals prefer to reside at the exterior cage surface, due mainly to the mismatch of their sizes with the boron cages, though the size match is not the only factor to determine their doping form. Furthermore, the infrared absorption spectra and ¹¹B nuclear magnetic resonance spectra of the three new M@B _n complexes were computed to assist future experimental characterization.

Open image in new window

Graphical Abstract Putting more metals into medium-sized boron cages!