Search

Shortly after the completion of the human genome project in 2003, the Encode project was launched. The project was set out to identify the functional elements in the human genome, and unexpectedly it was found that >80% of the genome is transcribed. The Encode project identified those transcribed regions of the genome to be encoded by non-coding RNAs (ncRNAs). With only 2% of the genome carrying gene-encoding proteins, the conundrum was then, what is the function, if any, of these non-coding regions of the genome? These ncRNAs included both short and long RNAs. The focus of this review will be on antisense long non-coding RNAs (lncRNAs), as these transcripts have been observed to play a role in gene expression of protein-coding genes. Some lncRNAs have been found to regulate protein-coding gene transcription at the epigenetic level, whereby they suppress transcription through the recruitment of protein complexes to target loci in the genome. Conversely, there are lncRNAs that have a positive role in gene expression with less known about mechanism, and some lncRNAs have been shown to be involved in post-transcriptional processes. Additionally, lncRNAs have been observed to regulate their own expression in a positive feedback loop by functioning as a decoy. The biological significance of lncRNAs is only just now becoming evident, with many lncRNAs found to play a significant role in several human diseases.

The Walter Reed Army Institute of Research holds an annual summer STEM program called Gains in the Education of Mathematics and Science (GEMS) in which rising 7th-12th graders are mentored by undergraduate STEM majors (near-peer mentors - NPMs) who facilitate hands-on, inquiry-centered activities. To make GEMS accessible to underserved and underrepresented populations, we recruit both students and NPMs from local, underserved communities and minority-serving institutions, while additionally broadcasting the opportunities to surrounding counties. We mitigate financial barriers to participation by offering both student and NPM stipends. Although GEMS is traditionally held in person, the COVID-19 pandemic led to the creation of virtual GEMS (eGEMS). We compared NPM and student survey responses for eGEMS to the prior year of in-person GEMS. Despite logistical differences, we maintained similar participant demographics, program elements, and shifts in attitudes towards STEM for all student groups while providing comparable personal and professional growth for NPMs. Going forward, though, eGEMS can be improved by incorporating more group work and use of laboratory tools alongside alleviating technical barriers. Furthermore, both eGEMS and in-person GEMS must increase recruitment amongst FARMS (free and reduced-price meals at school) recipients, English language learners, and potential first-generation college students to align with accessibility goals.

Emotion regulation is a key developmental skillset, but many existing measures rely on self-report or laboratory-based measurement approaches. This study aimed to develop a training and implementation protocol for the widely used Facial Expression Coding System (FACES) to be used in real-world settings with pre-recorded video data. A revised coding system with supplemental guidelines and training procedures was developed to use FACES with video data recorded in special education classrooms. This system resulted in adequate interrater reliability as well as reduced training time for coders. Specific training methods included close study of code definitions, coding of practice video, quantitative analysis of observation data to generate interrater agreement and kappa statistics, review of comparison charts to identify discrepancies between coder and training observations using the Noldus Observer XT software, and post-observation discussions. The revised FACES protocol and new training method presented here offer a more robust, efficient, and versatile tool that can be applied to systematic behavior observations conducted of students in real-world classroom settings.

Educational inequity is widely prevalent in United States (U.S.) public schools and creates barriers to STEM education for underserved and underrepresented populations, including racial minority, low-income, and first-generation college students. Scientists at the Walter Reed Army Institute of Research (WRAIR) recognized a need in its community, the greater Washington, DC metropolitan area, to improve access to high-quality STEM education, and founded the WRAIR Gains in the Education of Mathematics and Science (GEMS) program for this purpose. In pursuit of this goal, the GEMS program engages students using innovative learning strategies and authentic STEM experiences with the hopes of fostering interest in STEM and motivating more underserved and underrepresented students to persist in STEM education and career pathways. By 1995, WRAIR scientists began investigating how to bring science-enthusiastic but novice high school (HS) students into their laboratories where they could be mentored, along with providing a stipend to mitigate financial barriers; importantly, this process was funded by two Science Education Partnership Awards from 2001-2006. Each year, WRAIR's GEMS program now guides about 600-700 local middle and HS students to take part in hands-on, inquiry-based STEM laboratory investigations led by undergraduate "near peer mentors" (NPMs), so named due to their close age to participants. GEMS is now sustained at 14 sites nationwide through the U.S. Army Educational Outreach Program, and serve about 4,000 students and near-peer mentors annually. Recent evaluations of the program explore service to underrepresented groups in STEM and growth of the local program. Further evaluation of the nationwide programs reveals positive student feedback, especially regarding working with NPMs and hands-on learning.

Abstract Background Transcription initiation RNAs (tiRNAs) are nuclear localized 18 nucleotide RNAs derived from sequences immediately downstream of RNA polymerase II (RNAPII) transcription start sites. Previous reports have shown that tiRNAs are intimately correlated with gene expression, RNA polymerase II binding and behaviors, and epigenetic marks associated with transcription initiation, but not elongation. Results In the present work, we show that tiRNAs are commonly found at genomic CCCTC-binding factor (CTCF) binding sites in human and mouse, and that CTCF sites that colocalize with RNAPII are highly enriched for tiRNAs. To directly investigate the relationship between tiRNAs and CTCF we examined tiRNAs originating near the intronic CTCF binding site in the human tumor suppressor gene, p21 (cyclin-dependent kinase inhibitor 1A gene, also known as CDKN1A). Inhibition of CTCF-proximal tiRNAs resulted in increased CTCF localization and increased p21 expression, while overexpression of CTCF-proximal tiRNA mimics decreased CTCF localization and p21 expression. We also found that tiRNA-regulated CTCF binding influences the levels of trimethylated H3K27 at the alternate upstream p21 promoter, and affects the levels of alternate p21 (p21alt) transcripts. Extending these studies to another randomly selected locus with conserved CTCF binding we found that depletion of tiRNA alters nucleosome density proximal to sites of tiRNA biogenesis. Conclusions Taken together, these data suggest that tiRNAs modulate local epigenetic structure, which in turn regulates CTCF localization.

Abstract Background There is increasing evidence that tight blood glucose (BG) control improves outcomes in critically ill adults. Children show similar hyperglycaemic responses to surgery or critical illness. However it is not known whether tight control will benefit children given maturational differences and different disease spectrum. Methods/Design The study is an randomised open trial with two parallel groups to assess whether, for children undergoing intensive care in the UK aged ≤ 16 years who are ventilated, have an arterial line in-situ and are receiving vasoactive support following injury, major surgery or in association with critical illness in whom it is anticipated such treatment will be required to continue for at least 12 hours, tight control will increase the numbers of days alive and free of mechanical ventilation at 30 days, and lead to improvement in a range of complications associated with intensive care treatment and be cost effective. Children in the tight control group will receive insulin by intravenous infusion titrated to maintain BG between 4 and 7.0 mmol/l. Children in the control group will be treated according to a standard current approach to BG management. Children will be followed up to determine vital status and healthcare resources usage between discharge and 12 months post-randomisation. Information regarding overall health status, global neurological outcome, attention and behavioural status will be sought from a subgroup with traumatic brain injury (TBI). A difference of 2 days in the number of ventilator-free days within the first 30 days post-randomisation is considered clinically important. Conservatively assuming a standard deviation of a week across both trial arms, a type I error of 1% (2-sided test), and allowing for non-compliance, a total sample size of 1000 patients would have 90% power to detect this difference. To detect effect differences between cardiac and non-cardiac patients, a target sample size of 1500 is required. An economic evaluation will assess whether the costs of achieving tight BG control are justified by subsequent reductions in hospitalisation costs. Discussion The relevance of tight glycaemic control in this population needs to be assessed formally before being accepted into standard practice. Trial Registration Current Controlled Trials ISRCTN61735247

COVID-19 is a severe infectious disease that has claimed >150,000 lives and infected millions in the United States thus far, especially the elderly population. Emerging evidence has shown the virus to cause hemorrhagic and immunologic responses, which impact all organs, including lungs, kidneys, and the brain, as well as extremities. SARS-CoV-2 also affects patients', families', and society's mental health at large. There is growing evidence of re-infection in some patients. The goal of this paper is to provide a comprehensive review of SARS-CoV-2-induced disease, its mechanism of infection, diagnostics, therapeutics, and treatment strategies, while also focusing on less attended aspects by previous studies, including nutritional support, psychological, and rehabilitation of the pandemic and its management. We performed a systematic review of >1,000 articles and included 425 references from online databases, including, PubMed, Google Scholar, and California Baptist University's library. COVID-19 patients go through acute respiratory distress syndrome, cytokine storm, acute hypercoagulable state, and autonomic dysfunction, which must be managed by a multidisciplinary team including nursing, nutrition, and rehabilitation. The elderly population and those who are suffering from Alzheimer's disease and dementia related illnesses seem to be at the higher risk. There are 28 vaccines under development, and new treatment strategies/protocols are being investigated. The future management for COVID-19 should include B-cell and T-cell immunotherapy in combination with emerging prophylaxis. The mental health and illness aspect of COVID-19 are among the most important side effects of this pandemic which requires a national plan for prevention, diagnosis and treatment.

Human T cell leukaemia virus type-1 (HTLV-1) is an oncogenic retrovirus that causes lifelong infection in ~5–10 million individuals globally. It is endemic to certain First Nations populations of Northern and Central Australia, Japan, South and Central America, Africa, and the Caribbean region. HTLV-1 preferentially infects CD4+ T cells and remains in a state of reduced transcription, often being asymptomatic in the beginning of infection, with symptoms developing later in life. HTLV-1 infection is implicated in the development of adult T cell leukaemia/lymphoma (ATL) and HTLV-1-associated myelopathies (HAM), amongst other immune-related disorders. With no preventive or curative interventions, infected individuals have limited treatment options, most of which manage symptoms. The clinical burden and lack of treatment options directs the need for alternative treatment strategies for HTLV-1 infection. Recent advances have been made in the development of RNA-based antiviral therapeutics for Human Immunodeficiency Virus Type-1 (HIV-1), an analogous retrovirus that shares modes of transmission with HTLV-1. This review highlights past and ongoing efforts in the development of HTLV-1 therapeutics and vaccines, with a focus on the potential for gene therapy as a new treatment modality in light of its successes in HIV-1, as well as animal models that may help the advancement of novel antiviral and anticancer interventions. [ABSTRACT FROM AUTHOR]

This paper presents the theory, design, and application of a dual-branch series-diode analog pre-distortion (APD) linearizer to improve the linearity and efficiency of a K-band high-power amplifier (HPA). A first-of-its-kind, frequency-dependent large-signal APD model is presented. This model is used to evaluate different phase relationships between the linear and nonlinear branches, suggesting independent gain and phase expansion characteristics with this topology. This model is used to assess the impact of diode resistance, capacitance, and ideality factors on the APD characteristics. This feature is showcased with two similar GaAs diodes to find the best fit for the considered HPA. The selected diode is characterized and modeled between 1 and 26.5 GHz. A comprehensive APD design and simulation workflow is reported. Before fabrication, the simulated APD is evaluated with the measured HPA to verify linearity improvements. The APD prototype achieves a large-signal bandwidth of 6 GHz with 3 dB gain expansion and 8° phase rotation. This linearizer is demonstrated with a 17–21 GHz GaN HPA with 41 dBm output power and 35% efficiency. Using a wideband 750 MHz signal, this APD improves the noise–power ratio (NPR) by 6.5–8.2 dB over the whole HPA bandwidth. Next, the HPA output power is swept to compare APD vs. power backoff for the same NPR. APD improves the HPA output power by 1–2 W and efficiency by approximately 5–9% at 19 GHz. This efficiency improvement decreases by only 1–2% when including the APD post-amplifier consumption, thus suggesting overall efficiency and output power improvements with APD at K-band frequencies. [ABSTRACT FROM AUTHOR]

Animal-assisted interventions (AAI) are increasingly used in clinical and school settings to promote psychological and social-emotional well-being among youth. However, the precise role of youth-animal relationships in shaping developmental trajectories is understudied. Research is needed to expand human-centric models of child development, specifically to examine how youth relationships with animals may be ecological assets and identify potential processes of change underlying these relationships. This study analyzed interviews from 30 students attending a school for special education and mental health services that incorporates AAI. Results indicated that youth perceived their relationships with animals as contributing to enhanced social connection, which was perceived as leading to self-esteem and confidence, enjoyment, and self-regulation. Youth reported positive sensory experiences with animals as supporting self-regulation. These findings suggest that AAI may need to be structured to prioritize youths' ability to form positive social connections with animals and incorporate positive sensory experiences while limiting negative ones. [ABSTRACT FROM AUTHOR]

Electrical conductimetry and dynamic light scattering (DLS) were used to investigate the aggregation behaviors of four amino acid-based surfactants (AABSs; undecanoyl-glycine, undecanoyl-l-alanine, undecanoyl-l-valine, undecanoyl-l-leucine) in the presence of five linear diamine counterions (1,2-diaminoethane, 1,3-diaminopropane, 1,4-diaminobutane, 1,5-diaminopentane, 1,6-diaminohexane). Electrical conductimetry was used to measure the CMCs for each system, which ranged from 5.1 to 22.5 mM. With respect to counterions, the obtained CMCs decreased with increases in the interamine spacer length; this was attributed to the improved torsional binding flexibility in longer counterions. Strong linear correlations (mean R2 = 0.9443) were observed between the CMCs and predicted surfactant partition coefficients (logP; water/octanol), suggesting that micellization is primarily driven by the AABS's hydrophobicity for these systems. However, significant deviations in this linear relationship were observed for systems containing 1,2-diaminoethane, 1,4-diaminobutane, and 1,6-diaminohexane (p = 0.0774), suggesting altered binding dynamics for these counterions. pH measurements during the CMC determination experiments indicated the full deprotonation of the AABSs but did not give clear insights into the counterion protonation states, thus yielding an inconclusive evaluation of their charge stabilization effects during binding. However, DLS measurements revealed that the micellar size remained largely independent of the counterion length for counterions longer than 1,2-diaminoethane, with hydrodynamic diameters ranging from 2.2 to 2.8 nm. This was explained by the formation of charge-stabilized noncovalent dimers, with each counterion bearing a full +2 charge. Conductimetry-based estimates of the degrees of counterion binding (β) and free energies of micellization (ΔG°M) revealed that bulky AABSs exhibit preferential binding to counterions with an even number of methylene groups. It is proposed that when these counterions form noncovalent dimers, perturbations in their natural geometries result in the formation of a binding pocket that accommodates the AABS steric bulk. While the direct application of these systems remains to be seen, this study provides valuable insights into the structure–property relationships that govern AABS aggregation. [ABSTRACT FROM AUTHOR]

Acute and chronic stress each have physical manifestations in the human body that can lead to many negative health impacts. Today, reported stress levels worldwide are at an all-time high, spurring the search for non-pharmaceutical interventions to maintain healthy stress levels. In this study, we examined whether a pet dog's presence influences healthy adults' acute stress responses as assessed through self-reports, heart rate, plasma cortisol, and salivary alpha-amylase. Participating pet dog owners were randomly assigned to undergo the Trier Social Stress Test either with their pet dog or alone. While there was no group difference in perceived anxiety levels, participants undergoing the acute psychological stressor with their pet dogs present had significantly lower heart rates, lower plasma cortisol responses, and higher salivary alpha-amylase responses than people without their dogs. Those who participated without their dogs had a statistically flat alpha-amylase response, which is typically associated with extreme or pathological stress. These findings extend the potential effects of pet dogs beyond merely lowering their owner's stress levels to maintaining a healthier, balanced response across the sympathoadrenal medullary axis and hypothalamic–pituitary-adrenal axis. [ABSTRACT FROM AUTHOR]

Characterizing relative temporal and spatial variations in both the living and detrital components of bivalve food is required to predict bivalve growth across environments with contrasting seston compositions. The present article describes how remote sensing can be applied for such characterization, both over large spatial scales and fine spatial resolutions (i.e., farm scale; 10's of meters), thereby providing key information for bivalve aquaculture operations and site selection, including the restoration of native species. Using natural seawater samples collected from contrasting culture sites in North America and Europe, a simple model was developed to predict the total particulate organic matter (POM) available as food to bivalves from high-resolution remote-sensing images of coastal embayments which estimate chlorophyll (CHL) and turbidity, in which CHL acts as a proxy for living organics and turbidity as a measure of total suspended particulate matter (SPM). The resulting POM derived from satellite images, along with temperature and CHL, are then used as inputs to the bivalve bioenergetic model, ShellSIM, to predict the growth of Mytilus edulis, Crassostrea virginica, and Ostrea edulis along the coast of Maine, one of the most convoluted coasts in the United States, for aquaculture site selection. KEY WORDS: remote sensing, bivalve food, aquaculture site selection, particulate organic matter, turbidity, INTRODUCTION Modeling bivalve filter feeder growth in response to environmental variables in the coastal zone has applications to coastal zone management, and may include determination of estuary-wide carrying capacity, site [...]

This study assessed the validity of a set of social and emotional functioning constructs derived from the PYD short form (PYD‐SF) measure within a sample of children and adolescents with one or more mental health diagnoses related to social, emotional, or behavioral challenges. Using repeated measures design, responses to the PYD‐SF and the Social‐emotional assets and resilience scale were collected over two years from 369 students enrolled in special education. Multilevel factor analyses parsed within‐person variability from between‐person differences to understand the internal consistency of the target measures when used with clinical and special education populations. Associations between the social‐emotional constructs from the PYD‐SF and an assessment of social‐emotional assets and resilience were examined. A two‐level confirmatory factor analysis using seven PYD factors and the Social‐Emotional Assets and Resilience Scale indicated a very good model fit; all factor loadings were statistically significant at both levels. Results supported the validity and internal reliability of the social‐emotional constructs from the PYD‐SF measure for assessing the social and emotional competencies of youth with social, emotional, and/or behavioral challenges, but with the caveat that researchers should consider a higher degree of specificity when using it with youth from this population. The broad factors utilized in previous work should be reframed to emphasize separate types of connection. When keeping this revised framing in mind, the social‐emotional constructs of the PYD‐SF measure provide a tool for teachers, parents, and clinicians to use in treatment planning and identifying strategies to support positive development for diverse youth. [ABSTRACT FROM AUTHOR]

HIV-1 provirus integration results in a persistent latently infected reservoir that is recalcitrant to combined antiretroviral therapy (cART) with lifelong treatment being the only option. The "shock and kill" strategy aims to eradicate latent HIV by reactivating proviral gene expression in the context of cART treatment. Gene-specific transcriptional activation can be achieved using the RNA-guided CRISPR-Cas9 system comprising single guide RNAs (sgRNAs) with a nuclease-deficient Cas9 mutant (dCas9) fused to the VP64 transactivation domain (dCas9-VP64). We engineered this system to target 23 sites within the long terminal repeat promoter of HIV-1 and identified a "hotspot" for activation within the viral enhancer sequence. Activating sgRNAs transcriptionally modulated the latent proviral genome across multiple different in vitro latency cell models including T cells comprising a clonally integrated mCherry-IRES-Tat (LChIT) latency system. We detected consistent and effective activation of latent virus mediated by activator sgRNAs, whereas latency reversal agents produced variable activation responses. Transcriptomic analysis revealed dCas9-VP64/sgRNAs to be highly specific, while the well-characterized chemical activator TNFα induced widespread gene dysregulation. CRISPR-mediated gene activation represents a novel system which provides enhanced efficiency and specificity in a targeted latency reactivation strategy and represents a promising approach to a "functional cure" of HIV/AIDS.