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Epigenetic mechanisms, such as DNA methylation, have been proposed to mediate plastic responses in insects. The pea aphid (Acyrthosiphon pisum), like the majority of extant aphids, displays cyclical parthenogenesis - the ability of mothers to switch the reproductive mode of their offspring from reproducing parthenogenetically to sexually in response to environmental cues. The pea aphid genome encodes two paralogs of the de novo DNA methyltransferase gene, dnmt3a and dnmt3x. Here we show, using phylogenetic analysis, that this gene duplication event occurred at least 150 million years ago, likely after the divergence of the lineage leading to the Aphidomorpha (phylloxerans, adelgids and true aphids) from that leading to the scale insects (Coccomorpha) and that the two paralogs are maintained in the genomes of all aphids examined. We also show that the mRNA of both dnmt3 paralogs is maternally expressed in the viviparous aphid ovary. During development both paralogs are expressed in the germ cells of embryos beginning at stage 5 and persisting throughout development. Treatment with 5-azactyidine, a chemical that generally inhibits the DNA methylation machinery, leads to defects of oocytes and early-stage embryos and causes a proportion of later stage embryos to be born dead or die soon after birth. These phenotypes suggest a role for DNA methyltransferases in reproduction, consistent with that seen in other insects. Taking the vast evolutionary history of the dnmt3 paralogs, and the localisation of their mRNAs in the ovary, we suggest there is a role for dnmt3a and/or dnmt3x in early development, and a role for DNA methylation machinery in reproduction and development of the viviparous pea aphid.
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Mandated participation in parent education programs is a common practice across the United States for families who are undergoing divorce or who are involved in the child welfare or juvenile justice systems. Mandates to participate in parenting programs create substantial challenges for families, service providers, and service systems. Furthermore, the type and quality of the parenting services accessed vary widely, and their impacts need to be better understood. To address this need, an overview of the current state of the empirical literature on the impacts and outcomes of mandated parenting interventions for divorce and in child welfare and juvenile justice settings is provided, and suggestions to the field are offered to refine research related to mandated parenting programs. Given the challenges that mandated parenting programs pose, an alternative approach that views parenting through a public health lens is highlighted to build on the growing body of research on the impacts of population-wide applications of parenting support programs, and as a possible way to decrease the number of parents who are required to attend parenting programs. Opportunities to advance universal parenting support within a range of community settings, including primary care, early childhood education, and community mental health systems are offered. Gaps in knowledge regarding mechanisms of action of universal supports and impacts on the number of parents mandated to treatment are highlighted, and future directions for research in this area are suggested.
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Responsabilidad Parental , Padres , Humanos , Padres/educación , Niño , Programas Obligatorios , Divorcio , Delincuencia Juvenil/prevención & control , Educación no Profesional , Estados Unidos , Protección a la InfanciaRESUMEN
The brain exhibits rich oscillatory dynamics that vary across tasks and states, such as the EEG oscillations that define sleep. These oscillations play critical roles in cognition and arousal, but the brainwide mechanisms underlying them are not yet described. Using simultaneous EEG and fast fMRI in subjects drifting between sleep and wakefulness, we developed a machine learning approach to investigate which brainwide fMRI dynamics predict alpha (8-12 Hz) and delta (1-4 Hz) rhythms. We predicted moment-by-moment EEG power from fMRI activity in held-out subjects, and found that information about alpha power was represented by a remarkably small set of regions, segregated in two distinct networks linked to arousal and visual systems. Conversely, delta rhythms were diffusely represented on a large spatial scale across the cortex. These results identify distributed networks that predict delta and alpha rhythms, and establish a computational framework for investigating fMRI brainwide dynamics underlying EEG oscillations.
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The 1918 influenza pandemic was the most devastating respiratory pandemic in modern human history, with 50-100 million deaths worldwide. Here, we characterized the complete genomes of influenza A virus (IAV) from two fatal cases during the fall wave of 1918 influenza A (H1N1) pandemic in the United States, one from Walter Reed Army Hospital in Washington, DC, and the other from Camp Jackson, SC. The two complete IAV genomes were obtained by combining Illumina deep sequencing data from both total RNA and influenza viral genome-enriched libraries along with Sanger sequencing data from PCR across the sequencing gaps. This study confirms the previously reported 1918 IAV genomes and increases the total number of available complete or near-complete influenza viral genomes of the 1918 pandemic from four to six. Sequence comparisons among them confirm that the genomes of the 1918 pandemic virus were highly conserved during the main wave of the pandemic with geographic separation in North America and Europe. Metagenomic analyses revealed bacterial co-infections in both cases. Interestingly, in the Washington, DC, case, evidence is presented of the first reported Rhodococcus-influenza virus co-infection. IMPORTANCE: This study applied modern molecular biotechnology and high-throughput sequencing to formalin-fixed, paraffin-embedded autopsy lung samples from two fatal cases during the fall wave of the 1918 influenza A (H1N1) pandemic in the United States. Complete influenza genomes were obtained from both cases, which increases the total number of available complete or near-complete influenza genomes of the 1918 pandemic virus from four to six. Sequence analysis confirms that the 1918 pandemic virus was highly conserved during the main wave of the pandemic with geographic separation in North America and Europe. Metagenomic analyses revealed bacterial co-infections in both cases, including the first reported evidence of Rhodococcus-influenza co-infection. Overall, this study offers a detailed view at the molecular level of the very limited samples from the most devastating influenza pandemic in modern human history.
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Coinfección , Subtipo H1N1 del Virus de la Influenza A , Virus de la Influenza A , Gripe Humana , Infecciones por Orthomyxoviridae , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , ARN , Coinfección/genética , Adhesión en Parafina , Pulmón , Virus de la Influenza A/genética , Genoma Viral , Secuenciación de Nucleótidos de Alto Rendimiento , Formaldehído , AutopsiaRESUMEN
The aim of this study was to identify contextual factors that negatively affect activity and participation among powerchair football (PF) players. Thirty-seven semistructured interviews were conducted with PF players (Mage = 27.9 ± 8.2 years) in France (n = 18) and the United States (n = 19). Participants reported acute back and neck pain as the primary morbidities resulting from PF participation, with sustained atypical posture in the sport chair as the primary cause. Competition-related physical and mental stress were also identified as participation outcomes. Accompanying the many benefits of PF, participants recognized negative impacts of discomfort, physical fatigue, and mental fatigue. Interventions such as seating modifications, thermotherapy to combat pain, napping to combat acute physical stress, and mental preparation to manage state anxiety were all identified as prospective interventions.
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Fútbol , Deportes para Personas con Discapacidad , Humanos , Estudios Prospectivos , Estados Unidos , Adulto Joven , Adulto , Atletas , Dolor de Espalda , Dolor de Cuello , Estrés Fisiológico , Estrés PsicológicoRESUMEN
Diagnostic uncertainty and relapse rates in schizophrenia and schizoaffective disorder are relatively high, indicating the potential involvement of other pathological mechanisms that could serve as diagnostic indicators to be targeted for adjunctive treatment. This study aimed to seek objective evidence of methylenetetrahydrofolate reductase MTHFR C677T genotype-related bio markers in blood and urine. Vitamin and mineral cofactors related to methylation and indolamine-catecholamine metabolism were investigated. Biomarker status for 67 symptomatically well-defined cases and 67 asymptomatic control participants was determined using receiver operating characteristics, Spearman's correlation, and logistic regression. The 5.2%-prevalent MTHFR 677 TT genotype demonstrated a 100% sensitive and specific case-predictive biomarkers of increased riboflavin (vitamin B2) excretion. This was accompanied by low plasma zinc and indicators of a shift from low methylation to high methylation state. The 48.5% prevalent MTHFR 677 CC genotype model demonstrated a low-methylation phenotype with 93% sensitivity and 92% specificity and a negative predictive value of 100%. This model related to lower vitamin cofactors, high histamine, and HPLC urine indicators of lower vitamin B2 and restricted indole-catecholamine metabolism. The 46.3%-prevalent CT genotype achieved high predictive strength for a mixed methylation phenotype. Determination of MTHFR C677T genotype dependent functional biomarker phenotypes can advance diagnostic certainty and inform therapeutic intervention.
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Trastornos Psicóticos , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Ácido Fólico/metabolismo , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Genotipo , Biomarcadores , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/genética , Riboflavina/uso terapéutico , Riboflavina/genética , Vitaminas , CatecolaminasRESUMEN
Research evaluating the role of the 5,10-methylenetetrahydrofolate reductase (MTHFR C677T) gene in schizophrenia has not yet provided an extended understanding of the proximal pathways contributing to the 5-10-methylenetetrahydrofolate reductase (MTHFR) enzyme's activity and the distal pathways being affected by its activity. This review investigates these pathways, describing mechanisms relevant to riboflavin availability, trace mineral interactions, and the 5-methyltetrahydrofolate (5-MTHF) product of the MTHFR enzyme. These factors remotely influence vitamin cofactor activation, histamine metabolism, catecholamine metabolism, serotonin metabolism, the oxidative stress response, DNA methylation, and nicotinamide synthesis. These biochemical components form a broad interactive landscape from which candidate markers can be drawn for research inquiry into schizophrenia and other forms of mental illness. Candidate markers drawn from this functional biochemical background have been found to have biomarker status with greater than 90% specificity and sensitivity for achieving diagnostic certainty in schizophrenia and schizoaffective psychosis. This has implications for achieving targeted treatments for serious mental illness.
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Trastornos Psicóticos , Esquizofrenia , Humanos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Genotipo , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/genética , BiomarcadoresRESUMEN
Dopamine transmission from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) regulates important aspects of motivation and is influenced by the neuroimmune system. The neuroimmune system is a complex network of leukocytes, microglia and astrocytes that detect and remove foreign threats like bacteria or viruses and communicate with each other to regulate non-immune (e.g neuronal) cell activity through cytokine signaling. Inflammation is a key regulator of motivational states, though the effects of specific cytokines on VTA circuitry and motivation are largely unknown. Therefore, electrophysiology, neurochemical, immunohistochemical and behavioral studies were performed to determine the effects of the anti-inflammatory cytokine interleukin-10 (IL-10) on mesolimbic activity, dopamine transmission and conditioned behavior. IL-10 enhanced VTA dopamine firing and NAc dopamine levels via decreased VTA GABA currents in dopamine neurons. The IL-10 receptor was localized on VTA dopamine and non-dopamine cells. The IL-10 effects on dopamine neurons required post-synaptic phosphoinositide 3-kinase activity, and IL-10 appeared to have little-to-no efficacy on presynaptic GABA terminals. Intracranial IL-10 enhanced NAc dopamine levels in vivo and produced conditioned place aversion. Together, these studies identify the IL-10R on VTA dopamine neurons as a potential regulator of motivational states.
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Dopamina , Área Tegmental Ventral , Dopamina/farmacología , Neuronas Dopaminérgicas/fisiología , Interleucina-10/farmacología , Fosfatidilinositol 3-Quinasas , Núcleo Accumbens , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
Integration of APPs into care teams affects quality and safety for the oncology patient. Learn the best practices and understand the concepts of onboarding, orientation, mentorship, scope of practice, and top of license. Review how productivity and other incentive programs can be adapted to integrate APPs and focus on team-based metrics.
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Neoplasias , Enfermeras Practicantes , Humanos , Oncología Médica , Neoplasias/terapia , Mentores , PacientesRESUMEN
The application of nitrogen (N) and phosphorus (P) fertilizers to soils is required to maintain crop yields, so the sufficient and timely delivery of nutrients to match crop demand is important in fertilizer management. We quantified temporal growth responses of tomato plants with different rates of N and P application using high-throughput shoot phenotyping. The tomato plants were grown in soil that had organic, inorganic or a combination of sources of P incorporated. Additional N was added to each pot at low and high rates, 13 days after planting. At the same rate of total P application, the inorganic P source resulted in greater shoot growth at the early time points. Later on, the plants supplied with organic or mixed P sources grew faster than those that received the inorganic P source, resulting in comparable shoot biomass in all treatments at the time of destructive harvest. The shoot phenotyping data demonstrated that readily available soil P was important for early tomato growth while available N was more important in later stages of vegetative growth. These results suggest that a fertilizer formulation of combined inorganic and organic P sources may be able to sustain rapid and great shoot growth in tomato plants, while also reducing additional N input.
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Simultaneous EEG-fMRI is a powerful multimodal technique for imaging the brain, but its use in neurofeedback experiments has been limited by EEG noise caused by the MRI environment. Neurofeedback studies typically require analysis of EEG in real time, but EEG acquired inside the scanner is heavily contaminated with ballistocardiogram (BCG) artifact, a high-amplitude artifact locked to the cardiac cycle. Although techniques for removing BCG artifacts do exist, they are either not suited to real-time, low-latency applications, such as neurofeedback, or have limited efficacy. We propose and validate a new open-source artifact removal software called EEG-LLAMAS (Low Latency Artifact Mitigation Acquisition Software), which adapts and advances existing artifact removal techniques for low-latency experiments. We first used simulations to validate LLAMAS in data with known ground truth. We found that LLAMAS performed better than the best publicly-available real-time BCG removal technique, optimal basis sets (OBS), in terms of its ability to recover EEG waveforms, power spectra, and slow wave phase. To determine whether LLAMAS would be effective in practice, we then used it to conduct real-time EEG-fMRI recordings in healthy adults, using a steady state visual evoked potential (SSVEP) task. We found that LLAMAS was able to recover the SSVEP in real time, and recovered the power spectra collected outside the scanner better than OBS. We also measured the latency of LLAMAS during live recordings, and found that it introduced a lag of less than 50 ms on average. The low latency of LLAMAS, coupled with its improved artifact reduction, can thus be effectively used for EEG-fMRI neurofeedback. A limitation of the method is its use of a reference layer, a piece of EEG equipment which is not commercially available, but can be assembled in-house. This platform enables closed-loop experiments which previously would have been prohibitively difficult, such as those that target short-duration EEG events, and is shared openly with the neuroscience community.
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Camélidos del Nuevo Mundo , Neurorretroalimentación , Adulto , Animales , Humanos , Imagen por Resonancia Magnética/métodos , Electroencefalografía/métodos , Artefactos , Potenciales Evocados VisualesRESUMEN
[This corrects the article DOI: 10.1371/journal.pbio.3002035.].
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Cerebrospinal fluid (CSF) flow maintains healthy brain homeostasis, facilitating solute transport and the exchange of brain waste products. CSF flow is thus important for brain health, but the mechanisms that control its large-scale movement through the ventricles are not well understood. While it is well established that CSF flow is modulated by respiratory and cardiovascular dynamics, recent work has also demonstrated that neural activity is coupled to large waves of CSF flow in the ventricles during sleep. To test whether the temporal coupling between neural activity and CSF flow is in part due to a causal relationship, we investigated whether CSF flow could be induced by driving neural activity with intense visual stimulation. We manipulated neural activity with a flickering checkerboard visual stimulus and found that we could drive macroscopic CSF flow in the human brain. The timing and amplitude of CSF flow was matched to the visually evoked hemodynamic responses, suggesting neural activity can modulate CSF flow via neurovascular coupling. These results demonstrate that neural activity can contribute to driving CSF flow in the human brain and that the temporal dynamics of neurovascular coupling can explain this effect.
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Acoplamiento Neurovascular , Vigilia , Humanos , Encéfalo/fisiología , Acoplamiento Neurovascular/fisiología , Hemodinámica , Sueño , Imagen por Resonancia MagnéticaRESUMEN
Soil micronutrient availability, including zinc (Zn), is a limiting factor for crop yield. Arbuscular mycorrhizal (AM) fungi can improve host plant growth and nutrition through the mycorrhizal pathway of nutrient uptake. Although the physiology of Zn uptake through the mycorrhizal pathway is well established, the identity of the related molecular components are unknown. Here, RNA-seq analysis was used to identify genes differentially-regulated by AM colonization and soil Zn concentration in roots of Medicago truncatula. The putative Zn transporter gene MtZIP14 was markedly up-regulated in M. truncatula roots when colonized by Rhizophagus irregularis. MtZIP14 restored yeast growth under low Zn availability. Loss-of-function mutant plants (mtzip14) had reduced shoot biomass compared to the wild-type when colonized by AM fungi and grown under low and sufficient soil Zn concentration; at high soil Zn concentration, there were no genotypic differences in shoot biomass. The vesicular and arbuscular colonization of roots was lower in the mtzip14 plants regardless of soil Zn concentration. We propose that MtZIP14 is linked to AM colonization in M. truncatula plants, with the possibility that MtZIP14 function with AM colonization is linked to plant Zn nutrition.
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Medicago truncatula , Micorrizas , Micorrizas/fisiología , Medicago truncatula/metabolismo , Raíces de Plantas/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Suelo , SimbiosisRESUMEN
INTRODUCTION: Racial or ethnic minorities are underrepresented in many health care professions, including physical therapy. Understanding the experiences of minority students in graduate education provides insight into how physical therapy educational programs can promote diversity, equity, and inclusion, which are factors that have been shown to improve patient outcomes. The purpose of this study is to qualitatively analyze and describe the lived experiences of Black student physical therapists (PT) in Texas. REVIEW OF LITERATURE: Currently, there is a lack of qualitative research that investigates the experiences of Black students in physical therapy education in the United States. SUBJECTS: Nineteen Doctor of Physical Therapy students from 8 different physical therapy educational programs in Texas. METHODS: This qualitative study was conducted using a phenomenological approach. All participants took part in a focus group regarding their academic experiences. Students' dialogues were recorded and transcribed, and the researchers identified recurrent themes. RESULTS: After the analysis of focus group content, it was determined that the following 5 themes characterized the students' experiences: 1) Barriers to enrollment, 2) underrepresentation, 3) implicit and explicit racism, 4) code-switching, and 5) desired image. DISCUSSION AND CONCLUSION: There is evidence to suggest that Black or African American students are subject to unique pressures that negatively affect their experiences during their PT education. Efforts need to be made by higher education institutions and individuals to provide a more inclusive environment to best support those students. By gaining awareness of the results of this study, educators and students can begin dialogues on how to foster inclusivity and cultural understanding in physical therapy education. Ultimately, understanding the experiences of others can improve how individuals coexist in an increasingly diverse society, and how clinicians provide patient-centered, culturally aware care to patients and clients.
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Especialidad de Fisioterapia , Humanos , Estados Unidos , Texas , Investigación Cualitativa , Grupos Minoritarios , EstudiantesRESUMEN
Awakening from sleep reflects a profound transformation in neural activity and behavior. The thalamus is a key controller of arousal state, but whether its diverse nuclei exhibit coordinated or distinct activity at transitions in behavioral arousal state is unknown. Using fast fMRI at ultra-high field (7 Tesla), we measured sub-second activity across thalamocortical networks and within nine thalamic nuclei to delineate these dynamics during spontaneous transitions in behavioral arousal state. We discovered a stereotyped sequence of activity across thalamic nuclei and cingulate cortex that preceded behavioral arousal after a period of inactivity, followed by widespread deactivation. These thalamic dynamics were linked to whether participants subsequently fell back into unresponsiveness, with unified thalamic activation reflecting maintenance of behavior. These results provide an outline of the complex interactions across thalamocortical circuits that orchestrate behavioral arousal state transitions, and additionally, demonstrate that fast fMRI can resolve sub-second subcortical dynamics in the human brain.