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Centenarians a Happy Lot, Survey Says

Title: Centenarians a Happy Lot, Survey Says
Category: Health News
Created: 5/3/2013 12:35:00 PM
Last Editorial Review: 5/3/2013 12:00:00 AM




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Single Motherhood Doesn't Seem to Hinder Happiness

Title: Single Motherhood Doesn't Seem to Hinder Happiness
Category: Health News
Created: 4/26/2014 10:35:00 AM
Last Editorial Review: 4/28/2014 12:00:00 AM




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Kids' Happiness Doesn't Depend on 2 Natural Parents, Says Study

Title: Kids' Happiness Doesn't Depend on 2 Natural Parents, Says Study
Category: Health News
Created: 4/25/2014 2:35:00 PM
Last Editorial Review: 4/28/2014 12:00:00 AM




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Smartphone App Blocks Teens From Texting, Phoning While Driving

Title: Smartphone App Blocks Teens From Texting, Phoning While Driving
Category: Health News
Created: 4/27/2015 12:00:00 AM
Last Editorial Review: 4/28/2015 12:00:00 AM




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Kybella Approved for Double Chin

Title: Kybella Approved for Double Chin
Category: Health News
Created: 4/29/2015 12:00:00 AM
Last Editorial Review: 4/30/2015 12:00:00 AM




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First Generic Abilify Approved

Title: First Generic Abilify Approved
Category: Health News
Created: 4/29/2015 12:00:00 AM
Last Editorial Review: 4/30/2015 12:00:00 AM




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Nipple-Preserving Mastectomies Appear Safe for High-Risk Women: Study

Title: Nipple-Preserving Mastectomies Appear Safe for High-Risk Women: Study
Category: Health News
Created: 4/25/2016 12:00:00 AM
Last Editorial Review: 4/26/2016 12:00:00 AM




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Happy Mom Means Less Colicky Baby

Title: Happy Mom Means Less Colicky Baby
Category: Health News
Created: 4/28/2017 12:00:00 AM
Last Editorial Review: 5/1/2017 12:00:00 AM




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Rydapt Approved for Adults With Acute Myeloid Leukemia

Title: Rydapt Approved for Adults With Acute Myeloid Leukemia
Category: Health News
Created: 4/28/2017 12:00:00 AM
Last Editorial Review: 5/1/2017 12:00:00 AM




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Brineura Approved for Rare Genetic Illness Affecting Kids

Title: Brineura Approved for Rare Genetic Illness Affecting Kids
Category: Health News
Created: 4/28/2017 12:00:00 AM
Last Editorial Review: 5/1/2017 12:00:00 AM




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Health Tip: Choosing the Appropriate Gym

Title: Health Tip: Choosing the Appropriate Gym
Category: Health News
Created: 5/2/2018 12:00:00 AM
Last Editorial Review: 5/2/2018 12:00:00 AM




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Benlysta Approved for Children With Lupus

Title: Benlysta Approved for Children With Lupus
Category: Health News
Created: 4/29/2019 12:00:00 AM
Last Editorial Review: 4/30/2019 12:00:00 AM




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Dengue Vaccine Approved by FDA

Title: Dengue Vaccine Approved by FDA
Category: Health News
Created: 5/1/2019 12:00:00 AM
Last Editorial Review: 5/2/2019 12:00:00 AM




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FDA Approves New Type of Drug to Treat Migraines

Title: FDA Approves New Type of Drug to Treat Migraines
Category: Health News
Created: 12/23/2019 12:00:00 AM
Last Editorial Review: 12/24/2019 12:00:00 AM




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In Small Study, Rheumatoid Arthritis Drug Appears to Help COVID-19 Patients

Title: In Small Study, Rheumatoid Arthritis Drug Appears to Help COVID-19 Patients
Category: Health News
Created: 5/7/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM




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FDA Approves Diabetes Drug for Type of Heart Failure

The FDA today approved a new use for the diabetes drug, dapagliflozin (Farxiga), to reduce the risk of a hospital stay or death in people who have a type of heart failure.




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New Cholesterol Drug Approved by FDA

Title: New Cholesterol Drug Approved by FDA
Category: Health News
Created: 2/24/2020 12:00:00 AM
Last Editorial Review: 2/24/2020 12:00:00 AM




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New Members Appointed to PMC Advisory Committee

Four new members have been appointed to serve on the PMC National Advisory Committee: Philip Bourne, of the University of California, San Diego; Sophia Colamarino, an independent consultant in San Francisco; Paul Courant, of the University of Michigan; and Patricia Thibodeau, of Duke University. Each member will serve a 4-year term. The next meeting of the committee is scheduled for Friday, June 17, 2011. For more information on the committee, see PMC National Advisory Committee.




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PMC Advisory Committee Appoints New Members

The following new members have been appointed to serve on the PMC National Advisory Committee: Martha Bedard, Dean of Libraries at the University of New Mexico; and Lorraine Haricombe, Dean of Libraries at the University of Kansas and a member of SPARC's board. The next meeting of the committee is scheduled for June 19, 2012. For more information, see PMC National Advisory Committee.




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PMC Advisory Committee Appoints New Members

As of February 1, 2013, the following new members have been appointed to serve on the PMC National Advisory Committee: Ms. Sharon Terry of the Genetic Alliance; Dr. C. Victor Jongneel of the University of Illinois at Urbana-Champaign; Dr. Bevin Engelward of the Massachusetts Institute of Technology; Dr. Randall Morse of the Wadsworth Center; and Dr. Adelita Cantu of the University of Texas. For more information, see PMC National Advisory Committee.




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2 in 3 Women Unhappy With Their Breast Size. Could That Harm Their Health?

Title: 2 in 3 Women Unhappy With Their Breast Size. Could That Harm Their Health?
Category: Health News
Created: 2/6/2020 12:00:00 AM
Last Editorial Review: 2/6/2020 12:00:00 AM




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AHA News: Make Mother's Day Last All Year With Wellness and Appreciation

Title: AHA News: Make Mother's Day Last All Year With Wellness and Appreciation
Category: Health News
Created: 4/29/2020 12:00:00 AM
Last Editorial Review: 4/30/2020 12:00:00 AM




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First Treatment for Peanut Allergy Approved by FDA

Title: First Treatment for Peanut Allergy Approved by FDA
Category: Health News
Created: 2/3/2020 12:00:00 AM
Last Editorial Review: 2/3/2020 12:00:00 AM




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First Drug Approved for Treatment of Peanut Allergy in Children

Title: First Drug Approved for Treatment of Peanut Allergy in Children
Category: Health News
Created: 2/3/2020 12:00:00 AM
Last Editorial Review: 2/4/2020 12:00:00 AM




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Menopause May Someday Disappear as Women Postpone Pregnancy: Study

Title: Menopause May Someday Disappear as Women Postpone Pregnancy: Study
Category: Health News
Created: 4/24/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM




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Tukysa Approved for Unresectable, Metastatic HER2-Positive Breast Cancer

Title: Tukysa Approved for Unresectable, Metastatic HER2-Positive Breast Cancer
Category: Health News
Created: 4/20/2020 12:00:00 AM
Last Editorial Review: 4/21/2020 12:00:00 AM




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FDA Approves Trodelvy for Metastatic Triple-Negative Breast Cancer

Title: FDA Approves Trodelvy for Metastatic Triple-Negative Breast Cancer
Category: Health News
Created: 4/24/2020 12:00:00 AM
Last Editorial Review: 4/24/2020 12:00:00 AM




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Residents Perspectives on and Application of Dental Public Health Competencies Using Case-Based Methods

The aims of this study were to qualitatively assess dental public health (DPH) residents’ perspectives on teaching methods for DPH competencies and to develop and implement a case-based simulation to address those competencies, constructed on the basis of the qualitative assessment. Focus group discussions were conducted with 18 DPH residents enrolled in two university-based DPH programs. Topic areas discussed in the two focus groups were perceived value of DPH competencies, ways to acquire new DPH skills/abilities, and additional skills/abilities needed by DPH residents. The focus groups’ responses showed that the residents felt competent in the analytical thinking competencies such as research methodology and critiquing literature. They emphasized the importance of learning leadership skills and reported feeling somewhat uncertain about their mastery of the policy and advocacy and system evaluation competencies. Of the two distinct categories of DPH skills and competencies— analytical/critical thinking and practical competencies—these residents reported that a greater proportion of time needed to be devoted to integrating the practical competencies into their education. Based on the residents’ feedback, the authors developed a structured seminar series taking a case-based approach to simulate real-world DPH problems, using real and semi-hypothetical planning projects to meet the residents’ perceived needs and covering gaps between didactic learning and practice.




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Hiding in Plain Sight: an Approach to Treating Patients with Severe COVID-19 Infection

ABSTRACT

Patients with COVID-19 infection are at risk of acute respiratory disease syndrome (ARDS) and death. The tissue receptor for COVID-19 is ACE2, and higher levels of ACE2 can protect against ARDS. Angiotensin receptor blockers and statins upregulate ACE2. Clinical trials are needed to determine whether this drug combination might be used to treat patients with severe COVID-19 infection.




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Magnaporthe oryzae Auxiliary Activity Protein MoAa91 Functions as Chitin-Binding Protein To Induce Appressorium Formation on Artificial Inductive Surfaces and Suppress Plant Immunity

ABSTRACT

The appressoria that are generated by the rice blast fungus Magnaporthe oryzae in response to surface cues are important for successful colonization. Previous work showed that regulators of G-protein signaling (RGS) and RGS-like proteins play critical roles in appressorium formation. However, the mechanisms by which these proteins orchestrate surface recognition for appressorium induction remain unclear. Here, we performed comparative transcriptomic studies of Morgs mutant and wild-type strains and found that M. oryzae Aa91 (MoAa91), a homolog of the auxiliary activity family 9 protein (Aa9), was required for surface recognition of M. oryzae. We found that MoAA91 was regulated by the MoMsn2 transcription factor and that its disruption resulted in defects in both appressorium formation on the artificial inductive surface and full virulence of the pathogen. We further showed that MoAa91 was secreted into the apoplast space and was capable of competing with the immune receptor chitin elicitor-binding protein precursor (CEBiP) for chitin binding, thereby suppressing chitin-induced plant immune responses. In summary, we have found that MoAa91 is a novel signaling molecule regulated by RGS and RGS-like proteins and that MoAa91 not only governs appressorium development and virulence but also functions as an effector to suppress host immunity.

IMPORTANCE The rice blast fungus Magnaporthe oryzae generates infection structure appressoria in response to surface cues largely due to functions of signaling molecules, including G-proteins, regulators of G-protein signaling (RGS), mitogen-activated protein (MAP) kinase pathways, cAMP signaling, and TOR signaling pathways. M. oryzae encodes eight RGS and RGS-like proteins (MoRgs1 to MoRgs8), and MoRgs1, MoRgs3, MoRgs4, and MoRgs7 were found to be particularly important in appressorium development. To explore the mechanisms by which these proteins regulate appressorium development, we have performed a comparative in planta transcriptomic study and identified an auxiliary activity family 9 protein (Aa9) homolog that we named MoAa91. We showed that MoAa91 was secreted from appressoria and that the recombinant MoAa91 could compete with a chitin elicitor-binding protein precursor (CEBiP) for chitin binding, thereby suppressing chitin-induced plant immunity. By identifying MoAa91 as a novel signaling molecule functioning in appressorium development and an effector in suppressing host immunity, our studies revealed a novel mechanism by which RGS and RGS-like proteins regulate pathogen-host interactions.




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Toxin-Antitoxin Gene Pairs Found in Tn3 Family Transposons Appear To Be an Integral Part of the Transposition Module

ABSTRACT

Much of the diversity of prokaryotic genomes is contributed by the tightly controlled recombination activity of transposons (Tns). The Tn3 family is arguably one of the most widespread transposon families. Members carry a large range of passenger genes incorporated into their structures. Family members undergo replicative transposition using a DDE transposase to generate a cointegrate structure which is then resolved by site-specific recombination between specific DNA sequences (res) on each of the two Tn copies in the cointegrate. These sites also carry promoters controlling expression of the recombinase and transposase. We report here that a number of Tn3 members encode a type II toxin-antitoxin (TA) system, typically composed of a stable toxin and a labile antitoxin that binds the toxin and inhibits its lethal activity. This system serves to improve plasmid maintenance in a bacterial population and, until recently, was believed to be associated with bacterial persistence. At least six different TA gene pairs are associated with various Tn3 members. Our data suggest that several independent acquisition events have occurred. In contrast to most Tn3 family passenger genes, which are generally located away from the transposition module, the TA gene pairs abut the res site upstream of the resolvase genes. Although their role when part of Tn3 family transposons is unclear, this finding suggests a potential role for the embedded TA in stabilizing the associated transposon with the possibility that TA expression is coupled to expression of transposase and resolvase during the transposition process itself.

IMPORTANCE Transposable elements (TEs) are important in genetic diversification due to their recombination properties and their ability to promote horizontal gene transfer. Over the last decades, much effort has been made to understand TE transposition mechanisms and their impact on prokaryotic genomes. For example, the Tn3 family is ubiquitous in bacteria, molding their host genomes by the paste-and-copy mechanism. In addition to the transposition module, Tn3 members often carry additional passenger genes (e.g., conferring antibiotic or heavy metal resistance and virulence), and three were previously known to carry a toxin-antitoxin (TA) system often associated with plasmid maintenance; however, the role of TA systems within the Tn3 family is unknown. The genetic context of TA systems in Tn3 members suggests that they may play a regulatory role in ensuring stable invasion of these Tns during transposition.




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The ERS approach to e-cigarettes is entirely rational

The call for the European Respiratory Society (ERS) to change their e-cigarette and vaping policy, from honourable people with decades of experience fighting the evils of tobacco, is unfortunately misconceived. The three issues of greatest concern are acute toxicity, chronic toxicity and, most importantly, the effects on children and young people. The efficacy of e-cigarettes as an adjunct to smoking cessation are outwith the expertise of paediatric specialists, but we would ask for assurances that any benefits really do outweigh the risks to children and young people (below). Our comments on these key issues are as follows:




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A rational approach to e-cigarettes: challenging ERS policy on tobacco harm reduction

We wish to thank J. Britton and co-workers for responding to our editorial and giving us an opportunity to clarify our position as well as correct a few misunderstandings. We definitely share the same goal, which is to relieve Europe and the rest of the world from the terrible results of the tobacco epidemic. We also do not "blankly oppose e-cigarettes"; however, we strongly advocate against a harm reduction strategy including e-cigarettes as well as heated tobacco products [1]. As clinicians we all see reluctant smokers where e-cigarettes can be tried as a last resort for getting off cigarette smoking, but that is of little relevance for a general harm reduction strategy. We also agree that the UK has achieved a lot in the area of smoking cessation but would argue that this has been achieved by impressive tobacco control, not by the use of e-cigarettes, and that a country such as Australia, which has banned nicotine-containing e-cigarettes, has achieved similar results.




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A rational approach to e-cigarettes: challenging ERS policy on tobacco harm reduction

The respiratory community is united in its desire to reduce and eliminate the harm caused by tobacco smoking, which is at present on course to kill one billion people in the 21st century. The stated policy of the European Respiratory Society is to strive "constantly to promote strong and evidence-based policies to reduce the burden of tobacco related diseases". In our view, the recent ERS Tobacco Control Committee statement on tobacco harm reduction [1], though well-intentioned, appears to be based on a number of false premises and draws its conclusions from a partial account of available data. It also presents a false dichotomy between the provision of "conventional" tobacco control and harm reduction approaches. We therefore respond, in turn, to the seven arguments presented against the adoption of harm reduction in the Committee's statement.




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Worldwide survey of neurologists on approach to autoimmune encephalitis

Objective

To explore practice differences in the diagnosis and management of autoimmune encephalitis (AE), which is complicated by issues with sensitivity/specificity of antibody testing, nonspecific MRI/EEG/CSF findings, and competing differential diagnoses.

Methods

We used a worldwide electronic survey with practice-related demographic questions and clinical questions about 2 cases: (1) a 20-year-old woman with a neuropsychiatric presentation strongly suspicious of AE and (2) a 40-year-old man with new temporal lobe seizures and cognitive impairment. Responses among different groups were compared using multivariable logistic regression.

Results

We received 1,333 responses from 94 countries; 12.0% identified as neuroimmunologists. Case 1: those treating >5 AE cases per year were more likely to send antibodies in both serum and CSF (adjusted odds ratio [aOR] vs 0 per year: 3.29, 95% CI 1.31–8.28, p = 0.011), pursue empiric immunotherapy (aOR: 2.42, 95% CI 1.33–4.40, p = 0.004), and continue immunotherapy despite no response and negative antibodies at 2 weeks (aOR: 1.65, 95% CI 1.02–2.69, p = 0.043). Case 2: neuroimmunologists were more likely to send antibodies in both serum and CSF (aOR: 1.80, 95% CI 1.12–2.90, p = 0.015). Those seeing >5 AE cases per year (aOR: 1.86, 95% CI 1.22–2.86, p = 0.004) were more likely to start immunotherapy without waiting for antibody results.

Conclusions

Our results highlight the heterogeneous management of AE. Neuroimmunologists and those treating more AE cases generally take a more proactive approach to testing and immunotherapy than peers. Results highlight the need for higher-quality cohorts and trials to guide empiric immunotherapy, and evidence-based guidelines aimed at both experts and nonexperts. Because the average AE patient is unlikely to be first seen by a neuroimmunologist, ensuring greater uniformity in our approach to suspected cases is essential to ensure that patients are appropriately managed.




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Teenage Use of Smartphone Applications for Menstrual Cycle Tracking




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All for One and One Delivery Room Approach for All?

Multiple births are increasing in frequency related to advanced maternal age and fertility treatments, and they have an increased risk for congenital anomalies compared to singleton births. However, twins have the same congenital anomalies <15% of the time. Thus, having multiple births with discordant anomalies is a growing challenge for neonatologists. Although external anomalies can often be spotted quickly at delivery or sex differences between multiples can rapidly identify those with internal anomalies described on prenatal ultrasound, we present a case of male multiples, who would optimally receive different initial resuscitation strategies on the basis of the presence or absence of an internal anomaly. The similar size of 4 extremely preterm quadruplets raises concern for whether accurate, immediate identification of 1 neonate with a congenital diaphragmatic hernia will be reliable in the delivery room. Clinicians discuss the ethical considerations of an "all for one" approach to this resuscitation.




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Teenager With Abdominal Pain and Decreased Appetite

A 16-year-old girl presented to her primary care physician with a one-month history of decreased appetite and abdominal pain. She had normal bowel movements and no vomiting, but her periumbilical pain limited her ability to finish most meals. She had gradual weight loss over the previous 2 years, and during the previous 4 years, she intermittently received counseling for depression after the loss of her mother. Her initial physical examination and laboratory evaluation were unremarkable. She was referred to a nutritionist, adolescent medicine, and pediatric gastroenterology. Her presentation evolved over time, which ultimately led to a definitive diagnosis.




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Apparent Cause Analysis: A Safety Tool

Causal analysis is a core function of safety programs. Although established protocols exist for conducting root cause analysis for serious safety events, there is limited guidance for apparent cause analysis (ACA) in health care. At our institution, through a novel facilitated ACA approach, we aim to improve safety culture and provide a clear approach to address precursor safety events and near-miss safety events. We define facilitated ACA as limited investigation (scope and duration) of a safety event that resulted in little to no harm. These investigations require fewer resources and focus on preventive strategies. Our facilitated ACA model, with an operational algorithm and structured process, was developed and implemented at our tertiary-care, freestanding, urban pediatric hospital in 2018. Sixty-four ACAs were completed, and 83% were identified with the algorithm. Process measures, including time from event reporting to ACA launch (median 3 days; interquartile range 2–6 days), are tracked. Patient safety consultants averaged 5 hours to complete a facilitated ACA. A median of 3 disciplines or departments participated in each facilitated ACA. Through an iterative process, we implemented a structured process for facilitated ACA, and the model’s strength includes (1) right event, (2) right team, (3) right analysis, and (4) right action plans. This novel facilitated ACA model may support organizational cause analysis and improve safety culture with higher-reliability processes.




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Toward an Evolutionarily Appropriate Null Model: Jointly Inferring Demography and Purifying Selection [Population and Evolutionary Genetics]

The question of the relative evolutionary roles of adaptive and nonadaptive processes has been a central debate in population genetics for nearly a century. While advances have been made in the theoretical development of the underlying models, and statistical methods for estimating their parameters from large-scale genomic data, a framework for an appropriate null model remains elusive. A model incorporating evolutionary processes known to be in constant operation, genetic drift (as modulated by the demographic history of the population) and purifying selection, is lacking. Without such a null model, the role of adaptive processes in shaping within- and between-population variation may not be accurately assessed. Here, we investigate how population size changes and the strength of purifying selection affect patterns of variation at "neutral" sites near functional genomic components. We propose a novel statistical framework for jointly inferring the contribution of the relevant selective and demographic parameters. By means of extensive performance analyses, we quantify the utility of the approach, identify the most important statistics for parameter estimation, and compare the results with existing methods. Finally, we reanalyze genome-wide population-level data from a Zambian population of Drosophila melanogaster, and find that it has experienced a much slower rate of population growth than was inferred when the effects of purifying selection were neglected. Our approach represents an appropriate null model, against which the effects of positive selection can be assessed.




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Towards Innovative Design and Application of Recombinant Eimeria as a Vaccine Vector [Minireviews]

Efficient delivery of antigenic cargo to trigger protective immune responses is critical to the success of vaccination. Genetically engineered microorganisms, including virus, bacteria, and protozoa, can be modified to carry and deliver heterologous antigens to the host immune system. The biological vectors can induce a broad range of immune responses and enhance heterologous antigen-specific immunological outcomes. The protozoan genus Eimeria is widespread in domestic animals, causing serious coccidiosis. Eimeria parasites with strong immunogenicity are potent coccidiosis vaccine candidates and offer a valuable model of live vaccines against infectious diseases in animals. Eimeria parasites can also function as a vaccine vector. Herein, we review recent advances in design and application of recombinant Eimeria as a vaccine vector, which has been a topic of ongoing research in our laboratory. By recapitulating the establishment of an Eimeria transfection platform and its application, it will help lay the foundation for the future development of effective parasite-based vaccine delivery vectors and beyond.




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Loss of IKK Subunits Limits NF-{kappa}B Signaling in Reovirus-Infected Cells [Virus-Cell Interactions]

Viruses commonly antagonize innate immune pathways that are primarily driven by nuclear factor kappa B (NF-B), interferon regulatory factor (IRF), and the signal transducer and activator of transcription proteins (STAT) family of transcription factors. Such a strategy allows viruses to evade immune surveillance and maximize their replication. Using an unbiased transcriptome sequencing (RNA-seq)-based approach to measure gene expression induced by transfected viral genomic RNA (vgRNA) and reovirus infection, we discovered that mammalian reovirus inhibits host cell innate immune signaling. We found that, while vgRNA and reovirus infection both induce a similar IRF-dependent gene expression program, gene expression driven by the NF-B family of transcription factors is lower in infected cells. Potent agonists of NF-B such as tumor necrosis factor alpha (TNF-α) and vgRNA failed to induce NF-B-dependent gene expression in infected cells. We demonstrate that NF-B signaling is blocked due to loss of critical members of the inhibitor of kappa B kinase (IKK) complex, NF-B essential modifier (NEMO), and IKKβ. The loss of the IKK complex components prevents nuclear translocation and phosphorylation of NF-B, thereby preventing gene expression. Our study demonstrates that reovirus infection selectively blocks NF-B, likely to counteract its antiviral effects and promote efficient viral replication.

IMPORTANCE Host cells mount a response to curb virus replication in infected cells and prevent spread of virus to neighboring, as yet uninfected, cells. The NF-B family of proteins is important for the cell to mediate this response. In this study, we show that in cells infected with mammalian reovirus, NF-B is inactive. Further, we demonstrate that NF-B is rendered inactive because virus infection results in reduced levels of upstream intermediaries (called IKKs) that are needed for NF-B function. Based on previous evidence that active NF-B limits reovirus infection, we conclude that inactivating NF-B is a viral strategy to produce a cellular environment that is favorable for virus replication.




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Pseudorabies Virus Infection of Epithelial Cells Leads to Persistent but Aberrant Activation of the NF-{kappa}B Pathway, Inhibiting Hallmark NF-{kappa}B-Induced Proinflammatory Gene Expression [Virus-Cell Interactions]

The nuclear factor kappa B (NF-B) is a potent transcription factor, activation of which typically results in robust proinflammatory signaling and triggering of fast negative feedback modulators to avoid excessive inflammatory responses. Here, we report that infection of epithelial cells, including primary porcine respiratory epithelial cells, with the porcine alphaherpesvirus pseudorabies virus (PRV) results in the gradual and persistent activation of NF-B, illustrated by proteasome-dependent degradation of the inhibitory NF-B regulator IB and nuclear translocation and phosphorylation of the NF-B subunit p65. PRV-induced persistent activation of NF-B does not result in expression of negative feedback loop genes, like the gene for IBα or A20, and does not trigger expression of prototypical proinflammatory genes, like the gene for tumor necrosis factor alpha (TNF-α) or interleukin-6 (IL-6). In addition, PRV infection inhibits TNF-α-induced canonical NF-B activation. Hence, PRV infection triggers persistent NF-B activation in an unorthodox way and dramatically modulates the NF-B signaling axis, preventing typical proinflammatory gene expression and the responsiveness of cells to canonical NF-B signaling, which may aid the virus in modulating early proinflammatory responses in the infected host.

IMPORTANCE The NF-B transcription factor is activated via different key inflammatory pathways and typically results in the fast expression of several proinflammatory genes as well as negative feedback loop genes to prevent excessive inflammation. In the current report, we describe that infection of cells with the porcine alphaherpesvirus pseudorabies virus (PRV) triggers a gradual and persistent aberrant activation of NF-B, which does not result in expression of hallmark proinflammatory or negative feedback loop genes. In addition, although PRV-induced NF-B activation shares some mechanistic features with canonical NF-B activation, it also shows remarkable differences; e.g., it is largely independent of the canonical IB kinase (IKK) and even renders infected cells resistant to canonical NF-B activation by the inflammatory cytokine TNF-α. Aberrant PRV-induced NF-B activation may therefore paradoxically serve as a viral immune evasion strategy and may represent an important tool to unravel currently unknown mechanisms and consequences of NF-B activation.




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NF-{kappa}B and Keap1 Interaction Represses Nrf2-Mediated Antioxidant Response in Rabbit Hemorrhagic Disease Virus Infection [Pathogenesis and Immunity]

The rabbit hemorrhagic disease virus (RHDV), which belongs to the family Caliciviridae and the genus Lagovirus, causes lethal fulminant hepatitis in rabbits. RHDV decreases the activity of antioxidant enzymes regulated by Nrf2 in the liver. Antioxidants are important for the maintenance of cellular integrity and cytoprotection. However, the mechanism underlying the regulation of the Nrf2-antioxidant response element (ARE) signaling pathway by RHDV remains unclear. Using isobaric tags for relative and absolute quantification (iTRAQ) technology, the current study demonstrated that RHDV inhibits the induction of ARE-regulated genes and increases the expression of the p50 subunit of the NF-B transcription factor. We showed that RHDV replication causes a remarkable increase in reactive oxygen species (ROS), which is simultaneously accompanied by a significant decrease in Nrf2. It was found that nuclear translocation of Keap1 plays a key role in the nuclear export of Nrf2, leading to the inhibition of Nrf2 transcriptional activity. The p50 protein partners with Keap1 to form the Keap1-p50/p65 complex, which is involved in the nuclear translocation of Keap1. Moreover, upregulation of Nrf2 protein levels in liver cell nuclei by tert-butylhydroquinone (tBHQ) delayed rabbit deaths due to RHDV infection. Considered together, our findings suggest that RHDV inhibits the Nrf2-dependent antioxidant response via nuclear translocation of Keap1-NF-B complex and nuclear export of Nrf2 and provide new insight into the importance of oxidative stress during RHDV infection.

IMPORTANCE Recent studies have reported that rabbit hemorrhagic disease virus (RHDV) infection reduced Nrf2-related antioxidant function. However, the regulatory mechanisms underlying this process remain unclear. The current study showed that the NF-B p50 subunit partners with Keap1 to form the Keap1-NF-B complex, which plays a key role in the inhibition of Nrf2 transcriptional activity. More importantly, upregulated Nrf2 activity delayed the death of RHDV-infected rabbits, strongly indicating the importance of oxidative damage during RHDV infection. These findings may provide novel insights into the pathogenesis of RHDV.




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Emergence of self-organized multivortex states in flocks of active rollers [Applied Physical Sciences]

Active matter, both synthetic and biological, demonstrates complex spatiotemporal self-organization and the emergence of collective behavior. A coherent rotational motion, the vortex phase, is of great interest because of its ability to orchestrate well-organized motion of self-propelled particles over large distances. However, its generation without geometrical confinement has been a...




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Mimicry of a biophysical pathway leads to diverse pollen-like surface patterns [Applied Physical Sciences]

A ubiquitous structural feature in biological systems is texture in extracellular matrix that gains functions when hardened, for example, cell walls, insect scales, and diatom tests. Here, we develop patterned liquid crystal elastomer (LCE) particles by recapitulating the biophysical patterning mechanism that forms pollen grain surfaces. In pollen grains, a...




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Turning up the heat in turbulent thermal convection [Applied Physical Sciences]

Convection is buoyancy-driven flow resulting from unstable density stratification in the presence of a gravitational field. Beyond convection’s central role in myriad engineering heat transfer applications, it underlies many of nature’s dynamical designs on larger-than-human scales. For example, solar heating of Earth’s surface generates buoyancy forces that cause the winds...




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Whale sharks increase swimming effort while filter feeding, but appear to maintain high foraging efficiencies [RESEARCH ARTICLE]

David E. Cade, J. Jacob Levenson, Robert Cooper, Rafael de la Parra, D. Harry Webb, and Alistair D. M. Dove

Whale sharks (Rhincodon typus Smith 1828) – the largest extant fish species – reside in tropical environments, making them an exception to the general rule that animal size increases with latitude. How this largest fish thrives in tropical environments that promote high metabolism but support less robust zooplankton communities has not been sufficiently explained. We used open-source inertial measurement units (IMU) to log 397 hours of whale shark behavior in Yucatan, Mexico, at a site of both active feeding and intense wildlife tourism. Here we show that the strategies employed by whale sharks to compensate for the increased drag of an open mouth are similar to ram-feeders five orders of magnitude smaller and one order of magnitude larger. Presumed feeding constituted 20% of the total time budget of four sharks, with individual feeding bouts lasting up to 11 consecutive hrs. Compared to normal, sub-surface swimming, three sharks increased their stroke rate and amplitude while surface feeding, while one shark that fed at depth did not demonstrate a greatly increased energetic cost. Additionally, based on time-depth budgets, we estimate that aerial surveys of shark populations should consider including a correction factor of 3 to account for the proportion of daylight hours that sharks are not visible at the surface. With foraging bouts generally lasting several hours, interruptions to foraging during critical feeding periods may represent substantial energetic costs to these endangered species, and this study presents baseline data from which management decisions affecting tourist interactions with whale sharks may be made.




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Genetic lineage tracing with multiple DNA recombinases: A user's guide for conducting more precise cell fate mapping studies [Methods and Resources]

Site-specific recombinases, such as Cre, are a widely used tool for genetic lineage tracing in the fields of developmental biology, neural science, stem cell biology, and regenerative medicine. However, nonspecific cell labeling by some genetic Cre tools remains a technical limitation of this recombination system, which has resulted in data misinterpretation and led to many controversies in the scientific community. In the past decade, to enhance the specificity and precision of genetic targeting, researchers have used two or more orthogonal recombinases simultaneously for labeling cell lineages. Here, we review the history of cell-tracing strategies and then elaborate on the working principle and application of a recently developed dual genetic lineage-tracing approach for cell fate studies. We place an emphasis on discussing the technical strengths and caveats of different methods, with the goal to develop more specific and efficient tracing technologies for cell fate mapping. Our review also provides several examples for how to use different types of DNA recombinase–mediated lineage-tracing strategies to improve the resolution of the cell fate mapping in order to probe and explore cell fate–related biological phenomena in the life sciences.




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Pathogenesis and Management of Indirect Hyperbilirubinemia in Preterm Neonates Less Than 35 Weeks: Moving Toward a Standardized Approach

Premature infants have a higher incidence of indirect hyperbilirubinemia than term infants. Management of neonatal indirect hyperbilirubinemia in late preterm and term neonates has been well addressed by recognized, consensus-based guidelines. However, the extension of these guidelines to the preterm population has been an area of uncertainty because of limited evidence. This leads to variation in clinical practice and lack of recognition of the spectrum of bilirubin-induced neurologic dysfunction (BIND) in this population. Preterm infants are metabolically immature and at higher risk for BIND at lower bilirubin levels than their term counterparts. Early use of phototherapy to eliminate BIND and minimize the need for exchange transfusion is the goal of treatment in premature neonates. Although considered relatively safe, phototherapy does have side effects, and some NICUs tend to overuse phototherapy. In this review, we describe the epidemiology and pathophysiology of BIND in preterm neonates, and discuss our approach to standardized management of indirect hyperbilirubinemia in the vulnerable preterm population. The proposed treatment charts suggest early use of phototherapy in preterm neonates with the aim of reducing exposure to high irradiance levels, minimizing the need for exchange transfusions, and preventing BIND. The charts are pragmatic and have additional curves for stopping phototherapy and escalating its intensity. Having a standardized approach would support future research and quality improvement initiatives that examine dose and duration of phototherapy exposure with relation to outcomes.