Miracle-dz/UniFAR-FTUs huggingface dataset:
Pentatricopeptide-repeat family protein RF6 functions with hexokinase 6 to rescue rice cytoplasmic male sterility

Significance Plant cytoplasmic male sterility (CMS) and sterility restoration by nuclear restorer-of-fertility (Rf) genes provide a crucial breeding tool to harness hybrid vigor in many crops. Here, we identify RF6 as a novel pentatricopeptide repeat family protein that restores the fertility of Honglian CMS (HL-CMS), a major type of rice CMS used in breeding. We demonstrated that RF6 and hexokinase 6 function together in mitochondria to promote the processing of the aberrant CMS-associated transcript atp6-orfH79, thereby restoring the fertility of HL-CMS rice. This study links CMS restoration to hexokinase, providing novel insights into the mechanisms of CMS restoration, pollen development, mitochondria metabolism, and nuclear-cytoplasmic communication. In addition, the present study offers opportunities to further exploit rice heterosis in hybrid rice production. Cytoplasmic male sterility (CMS) has been extensively used for hybrid seed production in many major crops. Honglian CMS (HL-CMS) is one of the three major types of CMS in rice and has contributed greatly to food security worldwide. The HL-CMS trait is associated with an aberrant chimeric mitochondrial transcript, atp6-orfH79, which causes pollen sterility and can be rescued by two nonallelic restorer-of-fertility (Rf) genes, Rf5 or Rf6. Here, we report the identification of Rf6, which encodes a novel pentatricopeptide repeat (PPR) family protein with a characteristic duplication of PPR motifs 3–5. RF6 is targeted to mitochondria, where it physically associates with hexokinase 6 (OsHXK6) and promotes the processing of the aberrant CMS-associated transcript atp6-orfH79 at nucleotide 1238, which ensures normal pollen development and restores fertility. The duplicated motif 3 of RF6 is essential for RF6-OsHXK6 interactions, processing of the aberrant transcript, and restoration of fertility. Furthermore, reductions in the level of OsHXK6 result in atp6-orfH79 transcript accumulation and male sterility. Together these results reveal a novel mechanism for CMS restoration by which RF6 functions with OsHXK6 to restore HL-CMS fertility. The present study also provides insight into the function of hexokinase 6 in regulating mitochondrial RNA metabolism and may facilitate further exploitation of heterosis in rice.
NbCSPR underlies age-dependent immune responses to bacterial cold shock protein in Nicotiana benthamiana

Significance Plants detect pathogens by surface-localized receptors. Few such receptors are known. The coreceptor BRI1-ASSOCIATED KINASE 1 (BAK1) is a frequent member of activated receptor complexes. The proteomics strategy described here uses BAK1 as molecular bait to identify potential receptors that are specifically activated by pathogen components. We demonstrate this approach by identifying Nicotiana benthamiana RECEPTOR-LIKE PROTEIN REQUIRED FOR CSP22 RESPONSIVENESS (NbCSPR). We show that NbCSPR is required for immune responses initiated by the bacterial cold shock protein, confers age-dependent immunity against bacteria, and restricts the transformation of N. benthamiana cells by Agrobacterium. Manipulation of this gene will provide new options for disease control and genetic transformation of crop species. Plants use receptor kinases (RKs) and receptor-like proteins (RLPs) as pattern recognition receptors (PRRs) to sense pathogen-associated molecular patterns (PAMPs) that are typical of whole classes of microbes. After ligand perception, many leucine-rich repeat (LRR)-containing PRRs interact with the LRR-RK BRI1-ASSOCIATED KINASE 1 (BAK1). BAK1 is thus expected to interact with unknown PRRs. Here, we used BAK1 as molecular bait to identify a previously unknown LRR-RLP required for the recognition of the csp22 peptide derived from bacterial cold shock protein. We established a method to identify proteins that interact with BAK1 only after csp22 treatment. BAK1 was expressed transiently in Nicotiana benthamiana and immunopurified after treatment with csp22. BAK1-associated proteins were identified by mass spectrometry. We identified several proteins including known BAK1 interactors and a previously uncharacterized LRR-RLP that we termed RECEPTOR-LIKE PROTEIN REQUIRED FOR CSP22 RESPONSIVENESS (NbCSPR). This RLP associates with BAK1 upon csp22 treatment, and NbCSPR-silenced plants are impaired in csp22-induced defense responses. NbCSPR confers resistance to bacteria in an age-dependent and flagellin-induced manner. As such, it limits bacterial growth and Agrobacterium-mediated transformation of flowering N. benthamiana plants. Transgenic expression of NbCSPR into Arabidopsis thaliana conferred responsiveness to csp22 and antibacterial resistance. Our method may be used to identify LRR-type RKs and RLPs required for PAMP perception/responsiveness, even when the active purified PAMP has not been defined.
A Step‐by‐Step Multiple Stimuli‐Responsive Nanoplatform for Enhancing Combined Chemo‐Photodynamic Therapy

A robust and smart protoporphyrin-based polymer nanoplatform, which is capable of successively recognizing the variation of biological signals and reacting with them in a dynamic mode, is successfully developed. It combines the chemotherapy and photodynamic therapy in a same system, leading to a high treatment outcome while a low adverse side effect of therapeutic agent.
A new approach to study exhaled proteins as potential biomarkers for asthma

Cite this as: K. Bloemen, R. Van Den Heuvel, E. Govarts, J. Hooyberghs, V. Nelen, E. Witters, K. Desager and G. Schoeters, Clinical & Experimental Allergy, 2011 (41) 346–356.
Purely Organic Thermally Activated Delayed Fluorescence Materials for Organic Light‐Emitting Diodes

The design of thermally activated delayed fluorescence (TADF) materials both as emitters and as hosts is an exploding area of research. The replacement of phosphorescent metal complexes with inexpensive organic compounds in electroluminescent (EL) devices that demonstrate comparable performance metrics is paradigm shifting, as these new materials offer the possibility of developing low‐cost lighting and displays. Here, a comprehensive review of TADF materials is presented, with a focus on linking their optoelectronic behavior with the performance of the organic light‐emitting diode (OLED) and related EL devices. TADF emitters are cross‐compared within specific color ranges, with a focus on blue, green–yellow, orange–red, and white OLEDs. Organic small‐molecule, dendrimer, polymer, and exciplex emitters are all discussed within this review, as is their use as host materials. Correlations are provided between the structure of the TADF materials and their optoelectronic properties. The success of TADF materials has ushered in the next generation of OLEDs.
Genome-wide identification of CCA1 targets uncovers an expanded clock network in Arabidopsis

Significance The circadian clock, an endogenous time-keeping mechanism common to most species, allows organisms to coordinate biological processes with specific times of day. In plants, the role of the clock extends to almost every aspect of growth and development, including responses to biotic and abiotic stresses. The core molecular components and circuits of the clock have been well studied in the model organism Arabidopsis thaliana; however, how this mechanism connects to clock-controlled outputs remains poorly understood. Here, we performed a genome-wide characterization of the direct targets of a key clock component in Arabidopsis. Our results emphasize the broad role of the plant clock in regulating multiple biological functions and provide direct links between the oscillator and clock-regulated outputs. The circadian clock in Arabidopsis exerts a critical role in timing multiple biological processes and stress responses through the regulation of up to 80% of the transcriptome. As a key component of the clock, the Myb-like transcription factor CIRCADIAN CLOCK ASSOCIATED1 (CCA1) is able to initiate and set the phase of clock-controlled rhythms and has been shown to regulate gene expression by binding directly to the evening element (EE) motif found in target gene promoters. However, the precise molecular mechanisms underlying clock regulation of the rhythmic transcriptome, specifically how clock components connect to clock output pathways, is poorly understood. In this study, using ChIP followed by deep sequencing of CCA1 in constant light (LL) and diel (LD) conditions, more than 1,000 genomic regions occupied by CCA1 were identified. CCA1 targets are enriched for a myriad of biological processes and stress responses, providing direct links to clock-controlled pathways and suggesting that CCA1 plays an important role in regulating a large subset of the rhythmic transcriptome. Although many of these target genes are evening expressed and contain the EE motif, a significant subset is morning phased and enriched for previously unrecognized motifs associated with CCA1 function. Furthermore, this work revealed several CCA1 targets that do not cycle in either LL or LD conditions. Together, our results emphasize an expanded role for the clock in regulating a diverse category of genes and key pathways in Arabidopsis and provide a comprehensive resource for future functional studies.
Challenges in constraining anthropogenic aerosol effects on cloud radiative forcing using present-day spatiotemporal variability

A large number of processes are involved in the chain from emissions of aerosol precursor gases and primary particles to impacts on cloud radiative forcing. Those processes are manifest in a number of relationships that can be expressed as factors dlnX/dlnY driving aerosol effects on cloud radiative forcing. These factors include the relationships between cloud condensation nuclei (CCN) concentration and emissions, droplet number and CCN concentration, cloud fraction and droplet number, cloud optical depth and droplet number, and cloud radiative forcing and cloud optical depth. The relationship between cloud optical depth and droplet number can be further decomposed into the sum of two terms involving the relationship of droplet effective radius and cloud liquid water path with droplet number. These relationships can be constrained using observations of recent spatial and temporal variability of these quantities. However, we are most interested in the radiative forcing since the preindustrial era. Because few relevant measurements are available from that era, relationships from recent variability have been assumed to be applicable to the preindustrial to present-day change. Our analysis of Aerosol Comparisons between Observations and Models (AeroCom) model simulations suggests that estimates of relationships from recent variability are poor constraints on relationships from anthropogenic change for some terms, with even the sign of some relationships differing in many regions. Proxies connecting recent spatial/temporal variability to anthropogenic change, or sustained measurements in regions where emissions have changed, are needed to constrain estimates of anthropogenic aerosol impacts on cloud radiative forcing.
One-year outcomes and a cost-effectiveness analysis for smokers accessing group-based and pharmacy-led cessation services.

INTRODUCTION An observational study examining 1-year follow-up of clients of two National Health Service smoking cessation services in Glasgow was used to inform a cost-effectiveness analysis. One service involved 7 weeks of group-based support (n = 411) and the other consisted of up to 12 weeks of one-to-one counseling with pharmacists (n = 1,374). Pharmacological aids to quitting (e.g., nicotine replacement therapy) were available to all clients. METHODS Quit rates were calculated for each service at 52 weeks after the quit date, and these were used for an economic evaluation of both the annual and the lifetime cost-effectiveness of the pharmacy- and group-based interventions in comparison with a baseline "self-quit" scenario. The annual cost-effectiveness model established the incremental cost per 52-week quitter, while a Markov model was developed for the lifetime analysis to estimate the potential lifetime outcomes in terms of cost per quality-adjusted life years (QALY) gained, to account for the benefits quitters will receive in terms of extended life years and improvements in quality of life from smoking cessation. RESULTS The proportion of carbon monoxide-validated quitters from both services combined fell from 22.5% at 4-week follow-up to 3.6% at 52 weeks. The group service achieved a higher quit rate (6.3%) than the pharmacy service (2.8%) but was more intensive and required greater overhead costs. The lifetime analysis resulted in an incremental cost per QALY of £4,800 for the group support and £2,600 for pharmacy one-to-one counseling. CONCLUSIONS Despite disappointing 1-year quit rates, both services were considered to be highly cost-effective.
Affecting perceptions of harm and addiction among college waterpipe tobacco smokers.

INTRODUCTION The spread of waterpipe tobacco use among youth may be due in part to perceptions that waterpipe tobacco use is safer than other tobacco products, such as cigarettes. In two pilot studies, we sought to modify college waterpipe smokers' perceived risks and worry about waterpipe tobacco smoking. METHODS We conducted two web-based studies that varied whether college waterpipe users received information on (a) spread of and use of flavored tobacco in waterpipe and (b) harms of waterpipe smoking. Study 1 (N = 91) tested the "incremental" effects on perceptions of risk and worry of adding information about harms of waterpipe smoking to information on the spread of waterpipe and use of flavorings in the tobacco. Study 2 (N = 112) tested the effects on perceptions of risk and worry of reviewing information about harms of waterpipe smoking compared to a no information control group. In Study 1 only, we assessed as part of a 6-month follow-up (n = 70) the percentage of participants who reported no longer using waterpipe. RESULTS Pooling data from both studies, participants who received information about the harms of waterpipe smoking reported greater perceived risk and worry about harm and addiction and expressed a stronger desire to quit. In Study 1, 62% of participants in the experimental group versus 33% in the control group reported having stopped waterpipe use. CONCLUSIONS These are the first studies to show that perceptions of addiction and harm from waterpipe use can be modified using minimally intensive interventions; such interventions show promise at decreasing waterpipe use.
Photon‐Pair Generation with a 100 nm Thick Carbon Nanotube Film

Nonlinear optics based on bulk materials is the current technique of choice for quantum‐state generation and information processing. Scaling of nonlinear optical quantum devices is of significant interest to enable quantum devices with high performance. However, it is challenging to scale the nonlinear optical devices down to the nanoscale dimension due to relatively small nonlinear optical response of traditional bulk materials. Here, correlated photon pairs are generated in the nanometer scale using a nonlinear optical device for the first time. The approach uses spontaneous four‐wave mixing in a carbon nanotube film with extremely large Kerr‐nonlinearity (≈100 000 times larger than that of the widely used silica), which is achieved through careful control of the tube diameter during the carbon nanotube growth. Photon pairs with a coincidence to accidental ratio of 18 at the telecom wavelength of 1.5 µm are generated at room temperature in a ≈100 nm thick carbon nanotube film device, i.e., 1000 times thinner than the smallest existing devices. These results are promising for future integrated nonlinear quantum devices (e.g., quantum emission and processing devices).
PDK1–Akt pathway regulates radial neuronal migration and microtubules in the developing mouse neocortex

Significance In the developing mammalian neocortex, neurons migrate a long distance from their birthplace to the positions where they form appropriate layers and networks, and dysregulation of this process has been implicated in brain malformation and neurological diseases. Given the fine correlation between temporal order of various sequentially generated neuronal cell types and their spatial distribution, migration speed needs to be tightly controlled to achieve correct neocortical layering, although the underlying mechanisms remain unclear. Here we show that the serine/threonine kinase Akt and its activator phosphoinositide-dependent protein kinase 1 (PDK1) regulate the speed of locomotion of mouse neocortical neurons through the cortical plate. Our data suggest that the PDK1–Akt axis regulates microtubule organization, in part by regulating the cytoplasmic dynein/dynactin complex, in migrating neurons. Neurons migrate a long radial distance by a process known as locomotion in the developing mammalian neocortex. During locomotion, immature neurons undergo saltatory movement along radial glia fibers. The molecular mechanisms that regulate the speed of locomotion are largely unknown. We now show that the serine/threonine kinase Akt and its activator phosphoinositide-dependent protein kinase 1 (PDK1) regulate the speed of locomotion of mouse neocortical neurons through the cortical plate. Inactivation of the PDK1–Akt pathway impaired the coordinated movement of the nucleus and centrosome, a microtubule-dependent process, during neuronal migration. Moreover, the PDK1–Akt pathway was found to control microtubules, likely by regulating the binding of accessory proteins including the dynactin subunit p150glued. Consistent with this notion, we found that PDK1 regulates the expression of cytoplasmic dynein intermediate chain and light intermediate chain at a posttranscriptional level in the developing neocortex. Our results thus reveal an essential role for the PDK1–Akt pathway in the regulation of a key step of neuronal migration.
Exacerbations of severe asthma

Exacerbations occur frequently in severe asthma. They result in significant morbidity and can lead to hospitalization and death. Severe exacerbations can also lead to an accelerated decline in lung function. Phenotyping severe asthma can aid with both prognostication of exacerbation risk and maintenance treatment selection to minimize future risks of exacerbations in severe asthma. The rate of exacerbations differs by phenotype, and is most frequent in refractory eosinophilic asthma and early onset allergic asthma. Phenotype specific therapy can reduce exacerbations in both these forms of severe asthma. Exacerbations are multi‐component events. Each exacerbation represents an opportunity to assess and target treatment to the domains of airway pharmacotherapy, self‐management behaviour, risk factors, and relevant co‐morbidities.
Evolutionary origins of hepatitis A virus in small mammals

Significance The origins of human hepatitis A virus (HAV) are unknown. We conducted a targeted search for HAV-related viruses in small mammals sampled globally and discovered highly diversified viruses in bats, rodents, hedgehogs, and shrews. We demonstrate that these viruses share unique biological features with HAV, including structural, genomic, antigenic, and pathogenic properties. We found evidence of major shifts of HAV-related viruses between mammalian hosts in the past, suggesting both an origin of this viral genus in small mammals and a zoonotic origin of human HAV. Our data show that risk assessments for emerging viruses can benefit greatly from the analysis of viral infection patterns that evolved within animal reservoirs. Hepatitis A virus (HAV) is an ancient and ubiquitous human pathogen recovered previously only from primates. The sole species of the genus Hepatovirus, existing in both enveloped and nonenveloped forms, and with a capsid structure intermediate between that of insect viruses and mammalian picornaviruses, HAV is enigmatic in its origins. We conducted a targeted search for hepatoviruses in 15,987 specimens collected from 209 small mammal species globally and discovered highly diversified viruses in bats, rodents, hedgehogs, and shrews, which by pairwise sequence distance comprise 13 novel Hepatovirus species. Near-complete genomes from nine of these species show conservation of unique hepatovirus features, including predicted internal ribosome entry site structure, a truncated VP4 capsid protein lacking N-terminal myristoylation, a carboxyl-terminal pX extension of VP1, VP2 late domains involved in membrane envelopment, and a cis-acting replication element within the 3Dpol sequence. Antibodies in some bat sera immunoprecipitated and neutralized human HAV, suggesting conservation of critical antigenic determinants. Limited phylogenetic cosegregation among hepatoviruses and their hosts and recombination patterns are indicative of major hepatovirus host shifts in the past. Ancestral state reconstructions suggest a Hepatovirus origin in small insectivorous mammals and a rodent origin of human HAV. Patterns of infection in small mammals mimicked those of human HAV in hepatotropism, fecal shedding, acute nature, and extinction of the virus in a closed host population. The evolutionary conservation of hepatovirus structure and pathogenesis provide novel insight into the origins of HAV and highlight the utility of analyzing animal reservoirs for risk assessment of emerging viruses.
A perinatal emotional-health group for migrant women: lessons learned

Migrants have higher levels of depression and anxiety than non-migrants. Pregnant migrant women are especially vulnerable to emotional distress due to their social circumstances, isolation from family and culture of origin, and aspects of the pregnancy itself. This study aims to report the process of planning an emotional-health group program for migrant women in an antenatal clinic and discusses potential reasons for its poor uptake. The program was developed with the aim to provide education, reduce symptoms of anxiety, depression and stress, and to improve the social resources and connectedness of the women. The paper describes the pathways taken in developing the program, including a literature review and needs assessment and collaborative planning discussions across different key health services, recruitment, and review. Possible reasons for failure to implement the program included staff factors, cultural barriers, mistrust of healthcare services, family opposition, and difficulties with transport. Strategies to address these practical implementation issues and improve the acceptability of such programs in this population are discussed.