The influences of stomatal size and density on rice abiotic stress resilience.

A warming climate coupled with reductions in water availability and rising salinity are increasingly affecting rice (Oryza sativa) yields. Elevated temperatures combined with vapour pressure deficit (VPD) rises are causing stomatal closure, further reducing plant productivity and cooling. It is unclear what stomatal size (SS) and stomatal density (SD) will best suit all these environmental extremes. To understand how stomatal differences contribute to rice abiotic stress resilience, we screened the stomatal characteristics of 72 traditionally bred varieties. We found significant variation in SS, SD and calculated anatomical maximal stomatal conductance (gsmax ) but did not identify any varieties with SD and gsmax as low as transgenic OsEPF1oe plants. Traditionally bred varieties with high SD and small SS (resulting in higher gsmax ) typically had lower biomasses, and these plants were more resilient to drought than low SD and large SS plants, which were physically larger. None of the varieties assessed were as resilient to drought or salinity as low SD OsEPF1oe transgenic plants. High SD and small SS rice displayed faster stomatal closure during increasing temperature and VPD, but photosynthesis and plant cooling were reduced. Compromises will be required when choosing rice SS and SD to tackle multiple future environmental stresses.

Losing the Public, for Better or for Worse: A Lesson from John Everett Gordon (1890-1983) and John Rodman Paul (1893-1971).

The Covid-19 pandemic has laid bare a tension around scientific expertise that has major implications for the effectiveness of health systems. Critical engagement with this tension, however, is largely missing from the lessons and programs consolidating in the wake of the emergency. Lacking good frameworks for discussing the tension, the vague term "public trust" has proliferated into a buzzword that stands in for more articulate discussion. The tension between experts and the public is not new, however. It is useful to look back to the 1930s, when health experts identifying as "new epidemiologists" imagined a new modern science of epidemiology that, some believed, would resolve evident failures in public cooperation. Historical analysis of different approaches to the production and use of epidemiological knowledge in these years reveals a debate about power at the heart of epidemiology, and a critical framework for discussing the tension around epidemiological expertise in public health.

A genome-wide RNAi screen identifies factors required for distinct stages of C. elegans piRNA biogenesis.

In animals, piRNAs and their associated Piwi proteins guard germ cell genomes against mobile genetic elements via an RNAi-like mechanism. In Caenorhabditis elegans, 21U-RNAs comprise the piRNA class, and these collaborate with 22G RNAs via unclear mechanisms to discriminate self from nonself and selectively and heritably silence the latter. Recent work indicates that 21U-RNAs are post-transcriptional processing products of individual transcription units that produce ∼ 26-nucleotide capped precursors. However, nothing is known of how the expression of precursors is controlled or how primary transcripts give rise to mature small RNAs. We conducted a genome-wide RNAi screen to identify components of the 21U biogenesis machinery. Screening by direct, quantitative PCR (qPCR)-based measurements of mature 21U-RNA levels, we identified 22 genes important for 21U-RNA production, termed TOFUs (Twenty-One-u Fouled Ups). We also identified seven genes that normally repress 21U production. By measuring mature 21U-RNA and precursor levels for the seven strongest hits from the screen, we assigned factors to discrete stages of 21U-RNA production. Our work identifies for the first time factors separately required for the transcription of 21U precursors and the processing of these precursors into mature 21U-RNAs, thereby providing a resource for studying the biogenesis of this important small RNA class.

The Hepatitis C Clinical Exchange Network: A Local Health Department Partnership With Acute Care Hospitals to Promote Screening and Treatment of Hepatitis C Virus Infection.

CONTEXT: As of 2015, an estimated 116000 New York City (NYC) residents had chronic hepatitis C, many of them undiagnosed. Although effective medications have been available since 2014 with the advent of direct-acting antivirals, provider-based barriers to treatment remain. The NYC Department of Health and Mental Hygiene (Health Department) coordinated the Hepatitis C Clinical Exchange Network (HepCX) from 2015 to 2019. The main goal of HepCX was to promote hepatitis C screening and treatment by hospital-based providers. PROGRAM: The Health Department recruited hepatitis C champions (Champions) from acute care hospitals (n = 40) to promote improved hepatitis C care at their institutions. The Health Department provided technical assistance for hospitals to improve electronic medical record (EMR) systems and implement reflex RNA testing, coordinated trainings to increase capacity to treat hepatitis C, and distributed dashboards containing facility-specific testing and treatment metrics. IMPLEMENTATION: By the end of the project period (2019), most hospitals (36/40; 90%) reported having a screening alert for baby boomers in their EMR system and 34 (85%) reported performing reflex RNA testing after a positive hepatitis C antibody test. The Health Department coordinated opportunities for Champions to share their work with providers from network hospitals at meetings and webinars and provided clinical education on hepatitis C treatment in partnership with a local nonprofit organization focused on liver health. Facility-specific dashboards were distributed annually to hospital leadership. RNA confirmation testing increased from an average of 57% in 2015 to 85% in 2018. Treatment initiation rates remained similar over 2 years, averaging 39% in 2017 and 38% in 2018. DISCUSSION: HepCX was a multipronged initiative designed to promote hepatitis C testing and treatment initiation among providers at NYC acute care hospitals. Improvements were observed in confirmatory testing rates; however, treatment initiation rates did not change. Further efforts should be targeted to hospitals in need of additional resources for linkage to care and treatment of hepatitis C.

Application of an Imprint-and-Report Sensor Array for Detection of the Dietary Metabolite Trimethylamine N-Oxide and Its Precursors in Complex Mixtures.

Trimethylamine N-oxide (TMAO) is produced in the gut via metabolism of dietary betaine, choline, and carnitine, and elevated TMAO in plasma is associated with adverse health effects, including cardiovascular events. Currently, we lack high throughput methods for sensing these metabolites and detecting high TMAO. Thus, we have adapted our previously described "imprint-and-report" fluorescent sensing method using dynamic combinatorial libraries (DCLs) to create a sensor array for these four metabolites that functions at physiologically relevant concentrations. Templation of DCLs with dye and subsequent addition of analytes generates a fluorescent fingerprint for each metabolite and allows for differentiation via principal component analysis (PCA). Furthermore, we demonstrate that this system can be used to characterize mixtures of the metabolites in both buffer and human plasma samples. Using three to six DCLs, we can distinguish between plasma samples with healthy and elevated levels of TMAO.

The influence of stomatal morphology and distribution on photosynthetic gas exchange.

The intricate and interconnecting reactions of C3 photosynthesis are often limited by one of two fundamental processes: the conversion of solar energy into chemical energy, or the diffusion of CO2 from the atmosphere through the stomata, and ultimately into the chloroplast. In this review, we explore how the contributions of stomatal morphology and distribution can affect photosynthesis, through changes in gaseous exchange. The factors driving this relationship are considered, and recent results from studies investigating the effects of stomatal shape, size, density and patterning on photosynthesis are discussed. We suggest that the interplay between stomatal gaseous exchange and photosynthesis is complex, and that a disconnect often exists between the rates of CO2 diffusion and photosynthetic carbon fixation. The mechanisms that allow for substantial reductions in maximum stomatal conductance without affecting photosynthesis are highly dependent on environmental factors, such as light intensity, and could be exploited to improve crop performance.

Development of "Imprint-and-Report" Dynamic Combinatorial Libraries for Differential Sensing Applications.

Sensor arrays using synthetic receptors have found great utility in analyte detection, resulting from their ability to distinguish analytes based on differential signals via indicator displacement. However, synthesis and characterization of receptors for an array remain a bottleneck in the field. Receptor discovery has been streamlined using dynamic combinatorial libraries (DCLs), but the resulting receptors have primarily been utilized in isolation rather than as part of the entire library, with only a few examples that make use of the complexity of a library of receptors. Herein, we demonstrate a unique sensor array approach using "imprint-and-report" DCLs that obviates the need for receptor synthesis and isolation. This strategy leverages information stored in DCLs in the form of differential library speciation to provide a high-throughput method for both developing a sensor array and analyzing data for analyte differentiation. First, each DCL is templated with analyte to give an imprinted library, followed by in situ fluorescent indicator displacement analysis. We further demonstrate that the reverse strategy, imprinting with the fluorescent reporter followed by displacement with each analyte, provides a more sensitive method for differentiating analytes. We describe the development of this differential sensing system using the methylated Arg and Lys post-translational modifications (PTMs). Altogether, 19 combinations of 3-5 DCL data sets that discriminate all 7 PTMs were identified. Thus, a comparable sensor array workflow results in a larger payoff due to the immense information stored within multiple noncovalent networks.

Mimicking Biological Recognition: Lessons in Binding Hydrophilic Guests in Water.

Selective molecular recognition of hydrophilic guests in water plays a fundamental role in a vast number of biological processes, but synthetic mimicry of biomolecular recognition in water still proves challenging both in terms of achieving comparable affinities and selectivities. This Review highlights strategies that have been developed in the field of supramolecular chemistry to selectively and non-covalently bind three classes of biologically relevant molecules: nucleotides, carbohydrates, and amino acids. As several groups have systematically modified receptors for a specific guest, an evolutionary perspective is also provided in some cases. Trends in the most effective binding forces for each class are described, providing insight into selectivity and potential directions for future work.

Brucella Exposure Risk Events in 10 Clinical Laboratories, New York City, USA, 2015 to 2017.

From 2015 to 2017, 11 confirmed brucellosis cases were reported in New York City, leading to 10 Brucella exposure risk events (Brucella events) in 7 clinical laboratories (CLs). Most patients had traveled to countries where brucellosis is endemic and presented with histories and findings consistent with brucellosis. CLs were not notified that specimens might yield a hazardous organism, as the clinicians did not consider brucellosis until they were notified that bacteremia with Brucella was suspected. In 3 Brucella events, the CLs did not suspect that slow-growing, small Gram-negative bacteria might be harmful. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), which has a limited capacity to identify biological threat agents (BTAs), was used during 4 Brucella events, which accounted for 84% of exposures. In 3 of these incidents, initial staining of liquid media showed Gram-positive rods or cocci, including some cocci in chains, suggesting streptococci. Over 200 occupational exposures occurred when the unknown isolates were manipulated and/or tested on open benches, including by procedures that could generate infectious aerosols. During 3 Brucella events, the CLs examined and/or manipulated isolates in a biological safety cabinet (BSC); in each CL, the CL had previously isolated Brucella Centers for Disease Control and Prevention recommendations to prevent laboratory-acquired brucellosis (LAB) were followed; no seroconversions or LAB cases occurred. Laboratory assessments were conducted after the Brucella events to identify facility-specific risks and mitigations. With increasing MALDI-TOF MS use, CLs are well-advised to adhere strictly to safe work practices, such as handling and manipulating all slow-growing organisms in BSCs and not using MALDI-TOF MS for identification until BTAs have been ruled out.

(Cyclopentadienone)iron-Catalyzed Transfer Dehydrogenation of Symmetrical and Unsymmetrical Diols to Lactones.

Air-stable iron carbonyl compounds bearing cyclopentadienone ligands with varying substitution were explored as catalysts in dehydrogenative diol lactonization reactions using acetone as both the solvent and hydrogen acceptor. Two catalysts with trimethylsilyl groups in the 2- and 5-positions, [2,5-(SiMe3)2-3,4-(CH2)4(η4-C4C═O)]Fe(CO)3 (1) and [2,5-(SiMe3)2-3,4-(CH2)3(η4-C4C═O)]Fe(CO)3 (2), were found to be the most active, with 2 being the most selective in the lactonization of diols containing both primary and secondary alcohols. Lactones containing five-, six-, and seven-membered rings were successfully synthesized, and no over-oxidations to carboxylic acids were detected. The lactonization of unsymmetrical diols containing two primary alcohols occurred with catalyst 1, but selectivity was low based on alcohol electronics and modest based on alcohol sterics. Evidence for a transfer dehydrogenation mechanism was found, and insight into the origin of selectivity in the lactonization of 1°/2° diols was obtained. Additionally, spectroscopic evidence for a trimethylamine-ligated iron species formed in solution during the reaction was discovered.

Vaccine confidence in the time of COVID-19.

In the early months of the COVID-19 epidemic, some have wondered if the force of this global experience will solve the problem of vaccine refusal that has vexed and preoccupied the global public health community for the last several decades. Drawing on historical and epidemiological analyses, we critique contemporary approaches to reducing vaccine hesitancy and articulate our notion of vaccine confidence as an expanded way of conceptualizing the problem and how to respond to it. Intervening on the rush of vaccine optimism we see pervading present discourse around the COVID-19 epidemic, we call for a re-imagination of the culture of public health and the meaning of vaccine safety regulations. Public confidence in vaccination programs depends on the work they do for the community-social, political, and moral as well as biological. The concept of public health and its programs must be broader than the delivery of the vaccine technology itself. The narrative work and policy actions entailed in actualizing such changes will, we expect, be essential in achieving a true vaccine confidence, however the public reacts to the specific vaccine that may be developed for COVID-19.

Rice with reduced stomatal density conserves water and has improved drought tolerance under future climate conditions.

Much of humanity relies on rice (Oryza sativa) as a food source, but cultivation is water intensive and the crop is vulnerable to drought and high temperatures. Under climate change, periods of reduced water availability and high temperature are expected to become more frequent, leading to detrimental effects on rice yields. We engineered the high-yielding rice cultivar 'IR64' to produce fewer stomata by manipulating the level of a developmental signal. We overexpressed the rice epidermal patterning factor OsEPF1, creating plants with substantially reduced stomatal density and correspondingly low stomatal conductance. Low stomatal density rice lines were more able to conserve water, using c. 60% of the normal amount between weeks 4 and 5 post germination. When grown at elevated atmospheric CO2 , rice plants with low stomatal density were able to maintain their stomatal conductance and survive drought and high temperature (40°C) for longer than control plants. Low stomatal density rice gave equivalent or even improved yields, despite a reduced rate of photosynthesis in some conditions. Rice plants with fewer stomata are drought tolerant and more conservative in their water use, and they should perform better in the future when climate change is expected to threaten food security.

Molecular control of stomatal development.

Plants have evolved developmental plasticity which allows the up- or down-regulation of photosynthetic and water loss capacities as new leaves emerge. This developmental plasticity enables plants to maximise fitness and to survive under differing environments. Stomata play a pivotal role in this adaptive process. These microscopic pores in the epidermis of leaves control gas exchange between the plant and its surrounding environment. Stomatal development involves regulated cell fate decisions that ensure optimal stomatal density and spacing, enabling efficient gas exchange. The cellular patterning process is regulated by a complex signalling pathway involving extracellular ligand-receptor interactions, which, in turn, modulate the activity of three master transcription factors essential for the formation of stomata. Here, we review the current understanding of the biochemical interactions between the epidermal patterning factor ligands and the ERECTA family of leucine-rich repeat receptor kinases. We discuss how this leads to activation of a kinase cascade, regulation of the bHLH transcription factor SPEECHLESS and its relatives, and ultimately alters stomatal production.

Minotaur is critical for primary piRNA biogenesis.

Piwi proteins and their associated small RNAs are essential for fertility in animals. In part, this is due to their roles in guarding germ cell genomes against the activity of mobile genetic elements. piRNA populations direct Piwi proteins to silence transposon targets and, as such, form a molecular code that discriminates transposons from endogenous genes. Information ultimately carried by piRNAs is encoded within genomic loci, termed piRNA clusters. These give rise to long, single-stranded, primary transcripts that are processed into piRNAs. Despite the biological importance of this pathway, neither the characteristics that define a locus as a source of piRNAs nor the mechanisms that catalyze primary piRNA biogenesis are well understood. We searched an EMS-mutant collection annotated for fertility phenotypes for genes involved in the piRNA pathway. Twenty-seven homozygous sterile strains showed transposon-silencing defects. One of these, which strongly impacted primary piRNA biogenesis, harbored a causal mutation in CG5508, a member of the Drosophila glycerol-3-phosphate O-acetyltransferase (GPAT) family. These enzymes catalyze the first acylation step on the path to the production of phosphatidic acid (PA). Though this pointed strongly to a function for phospholipid signaling in the piRNA pathway, a mutant form of CG5508, which lacks the GPAT active site, still functions in piRNA biogenesis. We have named this new biogenesis factor Minotaur.

The first concussion crisis: head injury and evidence in early American football.

In the early 21st century, sports concussion has become a prominent public health problem, popularly labeled "The Concussion Crisis." Football-related concussion contributes much of the epidemiological burden and inspires much of the public awareness. Though often cast as a recent phenomenon, the crisis in fact began more than a century ago, as concussions were identified among footballers in the game's first decades. This early concussion crisis subsided-allowing the problem to proliferate-because work was done by football's supporters to reshape public acceptance of risk. They appealed to an American culture that permitted violence, shifted attention to reforms addressing more visible injuries, and legitimized football within morally reputable institutions. Meanwhile, changing demands on the medical profession made practitioners reluctant to take a definitive stance. Drawing on scientific journals, public newspapers, and personal letters of players and coaches, this history of the early crisis raises critical questions about solutions being negotiated at present.

Social suffering and the culture of compassion in a morally divided China.

This collection of essays opens a critical examination of compassionate acts responding to social suffering in the intensely complex moral context of a rapidly changing and globalizing China. Jeanne Shea describes self-compassion among older women in China as a post-revolutionary response to changing opportunities and resistance to consumerism. Khun Eng Kuah-Pearce's essay frames the Buddhist organizations as NGOs and shows compassion being mobilized and its acts being spiritual-philanthropic, not political. The next three papers illuminate the complexity of mobility in a moral sea of changing values. Even as modernity facilitates movement of people away from suffering, the grinding of entangled moral experiences within the mobile group can be the cause of suffering. Shu-Min Huang critiques 'cultural petrification' as the diasporic Yunnan Chinese community in Thailand attempt to preserve the cultural forms and procedures of the world they left behind. Likewise, Richard Madsen shows that the idea of a universalized cultural heritage fails in the face of the 'micro-ecologies'. And yet the modern impulse to universalize beyond China has important implications for transnational compassion and cooperation. The work of the humanitarian organization Médecins Sans Frontières in China, discussed by Kuah-Pearce and Guiheux, challenges the universality of global humanitarian actions. Following the series of essays threaded across intersections of compassion, suffering, and a morally-divided China, the collection closes by looking at the West. Iain Wilkinson discusses the origins of social suffering as a focus of the social sciences, as well as the difficulties of making engaged compassion its task in a morally-divided world.

Correction: Specific transfection of inflamed brain by macrophages: A new therapeutic strategy for neurodegenerative diseases.

[This corrects the article DOI: 10.1371/journal.pone.0061852.].

Longitudinal associations between smoking cessation medications and alcohol consumption among smokers in the International Tobacco Control Four Country survey.

BACKGROUND: Available evidence suggests that quitting smoking does not alter alcohol consumption. However, smoking cessation medications may have a direct impact on alcohol consumption independent of any effects on smoking cessation. Using an international longitudinal epidemiological sample of smokers, we evaluated whether smoking cessation medications altered alcohol consumption independent of quitting smoking. METHODS: Longitudinal data were analyzed from the International Tobacco Control Four Country (ITC-4) Survey between 2007 and 2008, a telephone survey of nationally representative samples of smokers from the United Kingdom, Australia, Canada, and the United States (n = 4,995). Quantity and frequency of alcohol consumption, use of smoking cessation medications (varenicline, nicotine replacement [NRT], and no medications), and smoking behavior were assessed across 2 yearly waves. Controlling for baseline drinking and changes in smoking status, we evaluated whether smoking cessation medications were associated with reduced alcohol consumption. RESULTS: Varenicline was associated with a reduced likelihood of any drinking compared with nicotine replacement (OR = 0.56; 95% CI = 0.34 to 0.94), and consuming alcohol once a month or more compared to nicotine replacement (OR = 0.43; 95% CI = 0.27 to 0.69) or no medication (OR = 0.63; 95% CI = 0.41 to 0.99). Nicotine replacement was associated with an increased likelihood of consuming alcohol once a month or more compared to no medication (OR = 1.14; 95% CI = 1.03 to 1.25). Smoking cessation medications were not associated with more frequent drinking (once a week or more) or typical quantity consumed per episode. Medication effects on drinking frequency were independent of smoking cessation. CONCLUSIONS: This epidemiological investigation demonstrated that varenicline was associated with a reduced frequency of alcohol consumption. Continued work should clarify under what conditions nicotine replacement therapies may increase or decrease patterns of alcohol consumption.

A preliminary study on the effect of combined nicotine replacement therapy on alcohol responses and alcohol self-administration.

BACKGROUND AND OBJECTIVES: Limiting alcohol consumption may help prevent alcohol-mediated smoking relapse in heavy drinking smokers. This pilot study examined whether combining a nicotine patch with nicotine nasal spray has stronger attenuating effects on alcohol response and consumption than a nicotine patch alone. METHODS: Twenty-two non-alcohol dependent heavy drinking smokers completed the double-blind cross-over, placebo-controlled study (21 mg nicotine patch + nicotine or placebo nasal spray). Six hours after 21 mg nicotine patch application, subjective and physiological responses to a priming drink (0.3 g/kg) were assessed, followed by two 1-hr alcohol self-administration periods, with possible consumption of up to 4 drinks per period (each 0.15 g/kg). Nasal spray (1 mg [active] or 0 mg [placebo] per dose) was administered 10 min prior to the priming dose and each self-administration period. RESULTS: Active nasal spray did not increase serum nicotine levels, compared with placebo administration. The number of drinks consumed did not differ by the nasal spray conditions. However, positive subjective responses to the priming drink were lower in the active nasal spray condition than the placebo nasal spray condition. During the self-administration period, urge to drink was also lower in the active spray condition than the placebo condition. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Augmenting the nicotine patch with nicotine nasal spray attenuated positive subjective alcohol response and craving and suggests that future studies should investigate whether these findings translate to a clinical setting.