epidecodeR: a functional exploration tool for epigenetic and epitranscriptomic regulation.

Recent technological advances in sequencing DNA and RNA modifications using high-throughput platforms have generated vast epigenomic and epitranscriptomic datasets whose power in transforming life science is yet fully unleashed. Currently available in silico methods have facilitated the identification, positioning and quantitative comparisons of individual modification sites. However, the essential challenge to link specific 'epi-marks' to gene expression in the particular context of cellular and biological processes is unmet. To fast-track exploration, we generated epidecodeR implemented in R, which allows biologists to quickly survey whether an epigenomic or epitranscriptomic status of their interest potentially influences gene expression responses. The evaluation is based on the cumulative distribution function and the statistical significance in differential expression of genes grouped by the number of 'epi-marks'. This tool proves useful in predicting the role of H3K9ac and H3K27ac in associated gene expression after knocking down deacetylases FAM60A and SDS3 and N6-methyl-adenosine-associated gene expression after knocking out the reader proteins. We further used epidecodeR to explore the effectiveness of demethylase FTO inhibitors and histone-associated modifications in drug abuse in animals. epidecodeR is available for downloading as an R package at https://bioconductor.riken.jp/packages/3.13/bioc/html/epidecodeR.html.

Design, Fabrication, and Characterization of Inkjet-Printed Organic Piezoresistive Tactile Sensor on Flexible Substrate.

In this paper, we propose a novel tactile sensor with a "fingerprint" design, named due to its spiral shape and dimensions of 3.80 mm × 3.80 mm. The sensor is duplicated in a four-by-four array containing 16 tactile sensors to form a "SkinCell" pad of approximately 45 mm by 29 mm. The SkinCell was fabricated using a custom-built microfabrication platform called the NeXus which contains additive deposition tools and several robotic systems. We used the NeXus' six-degrees-of-freedom robotic platform with two different inkjet printers to deposit a conductive silver ink sensor electrode as well as the organic piezoresistive polymer PEDOT:PSS-Poly (3,4-ethylene dioxythiophene)-poly(styrene sulfonate) of our tactile sensor. Printing deposition profiles of 100-micron- and 250-micron-thick layers were measured using microscopy. The resulting structure was sintered in an oven and laminated. The lamination consisted of two different sensor sheets placed back-to-back to create a half-Wheatstone-bridge configuration, doubling the sensitivity and accomplishing temperature compensation. The resulting sensor array was then sandwiched between two layers of silicone elastomer that had protrusions and inner cavities to concentrate stresses and strains and increase the detection resolution. Furthermore, the tactile sensor was characterized under static and dynamic force loading. Over 180,000 cycles of indentation were conducted to establish its durability and repeatability. The results demonstrate that the SkinCell has an average spatial resolution of 0.827 mm, an average sensitivity of 0.328 mΩ/Ω/N, expressed as the change in resistance per force in Newtons, an average sensitivity of 1.795 µV/N at a loading pressure of 2.365 PSI, and a dynamic response time constant of 63 ms which make it suitable for both large area skins and fingertip human-robot interaction applications.

Motor differences in autism during a human-robot imitative gesturing task.

BACKGROUND: Difficulty with imitative gesturing is frequently observed as a clinical feature of autism. Current practices for assessment of imitative gesturing ability-behavioral observation and parent report-do not allow precise measurement of specific components of imitative gesturing performance, instead relying on subjective judgments. Advances in technology allow researchers to objectively quantify the nature of these movement differences, and to use less socially stressful interaction partners (e.g., robots). In this study, we aimed to quantify differences in imitative gesturing between autistic and neurotypical development during human-robot interaction. METHODS: Thirty-five autistic (n = 19) and neurotypical (n = 16) participants imitated social gestures of an interactive robot (e.g., wave). The movements of the participants and the robot were recorded using an infrared motion-capture system with reflective markers on corresponding head and body locations. We used dynamic time warping to quantify the degree to which the participant's and robot's movement were aligned across the movement cycle and work contribution to determine how each joint angle was producing the movements. FINDINGS: Results revealed differences between autistic and neurotypical participants in imitative accuracy and work contribution, primarily in the movements requiring unilateral extension of the arm. Autistic individuals imitated the robot less accurately and used less work at the shoulder compared to neurotypical individuals. INTERPRETATION: These findings indicate differences in autistic participants' ability to imitate an interactive robot. These findings build on our understanding of the underlying motor control and sensorimotor integration mechanisms that support imitative gesturing in autism which may aid in identifying appropriate intervention targets.

In-Process Orbiting Laser-Assisted Technique for the Surface Finish in Material Extrusion-Based 3D Printing.

Material extrusion-based polymer 3D printing, one of the most commonly used additive manufacturing processes for thermoplastics and composites, has drawn extensive attention due to its capability and cost effectiveness. However, the low surface finish quality of the printed parts remains a drawback due to the nature of stacking successive layers along one direction and the nature of rastering of the extruded tracks of material. In this work, an in-process thermal radiation-assisted, surface reflow method is demonstrated that significantly improves the surface finish of the sidewalls of printed parts. It is observed that the surface finish of the printed part is drastically improved for both flat and curved surfaces. The effect of surface reflow on roughness reduction was characterized using optical profilometry and scanning electron microscopy (SEM), while the local heated spot temperature was quantified using a thermal camera.

Psychotropic drugs interaction with the lipid nanoparticle of COVID-19 mRNA therapeutics.

The messenger RNA (mRNA) vaccines for COVID-19, Pfizer-BioNTech and Moderna, were authorized in the US on an emergency basis in December of 2020. The rapid distribution of these therapeutics around the country and the world led to millions of people being vaccinated in a short time span, an action that decreased hospitalization and death but also heightened the concerns about adverse effects and drug-vaccine interactions. The COVID-19 mRNA vaccines are of particular interest as they form the vanguard of a range of other mRNA therapeutics that are currently in the development pipeline, focusing both on infectious diseases as well as oncological applications. The Vaccine Adverse Event Reporting System (VAERS) has gained additional attention during the COVID-19 pandemic, specifically regarding the rollout of mRNA therapeutics. However, for VAERS, absence of a reporting platform for drug-vaccine interactions left these events poorly defined. For example, chemotherapy, anticonvulsants, and antimalarials were documented to interfere with the mRNA vaccines, but much less is known about the other drugs that could interact with these therapeutics, causing adverse events or decreased efficacy. In addition, SARS-CoV-2 exploitation of host cytochrome P450 enzymes, reported in COVID-19 critical illness, highlights viral interference with drug metabolism. For example, patients with severe psychiatric illness (SPI) in treatment with clozapine often displayed elevated drug levels, emphasizing drug-vaccine interaction.

Bromodomains in Human-Immunodeficiency Virus-Associated Neurocognitive Disorders: A Model of Ferroptosis-Induced Neurodegeneration.

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) comprise a group of illnesses marked by memory and behavioral dysfunction that can occur in up to 50% of HIV patients despite adequate treatment with combination antiretroviral drugs. Iron dyshomeostasis exacerbates HIV-1 infection and plays a major role in Alzheimer's disease pathogenesis. In addition, persons living with HIV demonstrate a high prevalence of neurodegenerative disorders, indicating that HAND provides a unique opportunity to study ferroptosis in these conditions. Both HIV and combination antiretroviral drugs increase the risk of ferroptosis by augmenting ferritin autophagy at the lysosomal level. As many viruses and their proteins exit host cells through lysosomal exocytosis, ferroptosis-driving molecules, iron, cathepsin B and calcium may be released from these organelles. Neurons and glial cells are highly susceptible to ferroptosis and neurodegeneration that engenders white and gray matter damage. Moreover, iron-activated microglia can engage in the aberrant elimination of viable neurons and synapses, further contributing to ferroptosis-induced neurodegeneration. In this mini review, we take a closer look at the role of iron in the pathogenesis of HAND and neurodegenerative disorders. In addition, we describe an epigenetic compensatory system, comprised of bromodomain-containing protein 4 (BRD4) and microRNA-29, that may counteract ferroptosis by activating cystine/glutamate antiporter, while lowering ferritin autophagy and iron regulatory protein-2. We also discuss potential interventions for lysosomal fitness, including ferroptosis blockers, lysosomal acidification, and cathepsin B inhibitors to achieve desirable therapeutic effects of ferroptosis-induced neurodegeneration.

Ethics reporting in forensic science research publications - A review.

An essential element of compliance with ethical standards in scientific research is the reporting of a verifiable declaration of ethical approval and, when human subjects are involved - informed consent, in published works. The level of reporting of ethical permission for research published in forensic and investigative sciences journals has not been explored to date. Hence, we examined the reporting of ethical approval and informed consent in original research utilising human or animal subjects published in six forensic science journals from 2010 to 2019. We identified 10,192 articles and retained 3010 that satisfied the inclusion criteria of utilising human (91.2%), or animal (7.0%) or both (1.8%) subjects or tissues in experiments. Just over a third (1079/3010) of all studies declared obtaining ethical approval, with 927 (85.9%) of those indicating the name of the ethical committee, but only 392 (36%) provided an approval code. Furthermore, while consent was said to have been sought in 527 (17.5%) of studies, only 155 of those reported that written informed consent was obtained, eleven stated oral (verbal) consent, while the remaining 357 studies (67.7%) did not report the process used to gain consent. Ethical approval reporting rates differed between different research types, availability of financial support and whether authors were affiliated to academia or industry. The results demonstrate a low level of declaration of ethical approval and informed consent in forensic science research and publication, requiring urgent rectification. We support the adoption of the model proposed by Forensic Science International: Genetics as baseline recommendations to facilitate consistent nomenclature, transparency, and standard of ethical reporting in forensic science.

Ciliary photoreceptors in sea urchin larvae indicate pan-deuterostome cell type conservation.

BACKGROUND: The evolutionary history of cell types provides insights into how morphological and functional complexity arose during animal evolution. Photoreceptor cell types are particularly broadly distributed throughout Bilateria; however, their evolutionary relationship is so far unresolved. Previous studies indicate that ciliary photoreceptors are homologous at least within chordates, and here, we present evidence that a related form of this cell type is also present in echinoderm larvae. RESULTS: Larvae of the purple sea urchin Strongylocentrotus purpuratus have photoreceptors that are positioned bilaterally in the oral/anterior apical neurogenic ectoderm. Here, we show that these photoreceptors express the transcription factor Rx, which is commonly expressed in ciliary photoreceptors, together with an atypical opsin of the GO family, opsin3.2, which localizes in particular to the cilia on the cell surface of photoreceptors. We show that these ciliary photoreceptors express the neuronal marker synaptotagmin and are located in proximity to pigment cells. Furthermore, we systematically identified additional transcription factors expressed in these larval photoreceptors and found that a majority are orthologous to transcription factors expressed in vertebrate ciliary photoreceptors, including Otx, Six3, Tbx2/3, and Rx. Based on the developmental expression of rx, these photoreceptors derive from the anterior apical neurogenic ectoderm. However, genes typically involved in eye development in bilateria, including pax6, six1/2, eya, and dac, are not expressed in sea urchin larval photoreceptors but are instead co-expressed in the hydropore canal. CONCLUSIONS: Based on transcription factor expression, location, and developmental origin, we conclude that the sea urchin larval photoreceptors constitute a cell type that is likely homologous to the ciliary photoreceptors present in chordates.

Comparison of Isohelix™ and Rayon swabbing systems for touch DNA recovery from metal surfaces.

A previous study evaluating two swabbing systems found that DNA was best recovered from sterile metal substrates using an Isohelix™ swab wetted with isopropyl alcohol rather than a Rayon swab with water as the wetting agent. We tested the same swabbing systems on metal (aluminum, brass, and stainless steel) and plastic substrates in a regularly touched environment to simulate the non-deliberate transfer of touch evidence likely seen in a casework scenario, to ascertain the performance of these swabs in an uncontrolled situation. Higher amounts of touch DNA were recovered with Isohelix™ swabs (0.5 - 3.3 ng) compared to Rayon swabs (0.13 - 1.2 ng). The Isohelix™ swabbing system was found to significantly recover more touch DNA (p = 0.04) from the metal substrates than the Rayon swabbing system, consistent with the findings of our previous work. The results contribute to our understanding of the impact of sample collection techniques on touch DNA recovery from problematic metal surfaces and suggest that supplemental cleaning of substrates as a precautionary step against the spread of infections may affect touch DNA persistence and the recovery efficiency of swabs.

Evaluation of the efficiency of Isohelix™ and Rayon swabs for recovery of DNA from metal surfaces.

PURPOSE: We investigated the recovery and extraction efficiency of DNA from three metal surfaces (brass, copper, steel) relevant to forensic casework, and plastic (control) using two different swabbing systems; Rayon and Isohelix™ swabs, with sterile water and isopropyl alcohol respectively, as the wetting solutions. METHODS: Twenty nanograms of human genomic DNA were applied directly to Isohelix™ and Rayon swabs; and to the metal and plastic substrates. All substrates were left to dry for 24 h, followed by single wet swabbing and extraction with the DNA IQ™ System. DNA extracts were quantified using real time quantitative PCR assays with SYBR green chemistry. RESULTS: DNA was extracted from directly seeded Isohelix™ swabs with a high efficiency of 98%, indicating effective DNA-release from the swab into the extraction buffer. In contrast, only 58% of input DNA was recovered from seeded Rayon swabs, indicating higher DNA retention by these swabs. Isohelix™ swabs recovered 32 - 53% of DNA from metal surfaces, whilst the Rayon swabs recovered 11-29%. DNA recovery was lowest from copper and highest from brass. Interestingly, Rayon swabs appeared to collect more DNA from the plastic surface than Isohelix™ swabs, however, due to the lower release of DNA from Rayon swabs they returned less DNA overall following extraction than Isohelix™ swabs. CONCLUSION: These results demonstrate that DNA samples deposited on metal surfaces can be more efficiently recovered using Isohelix™ swabs wetted with isopropyl alcohol than Rayon swabs wetted with sterile water, although recovery is affected by the substrate type.

Acceptability of Using a Robotic Nursing Assistant in Health Care Environments: Experimental Pilot Study.

BACKGROUND: According to the US Bureau of Labor Statistics, nurses will be the largest labor pool in the United States by 2022, and more than 1.1 million nursing positions have to be filled by then in order to avoid a nursing shortage. In addition, the incidence rate of musculoskeletal disorders in nurses is above average in comparison with other occupations. Robot-assisted health care has the potential to alleviate the nursing shortage by automating mundane and routine nursing tasks. Furthermore, robots in health care environments may assist with safe patient mobility and handling and may thereby reduce the likelihood of musculoskeletal disorders. OBJECTIVE: This pilot study investigates the perceived ease of use and perceived usefulness (acceptability) of a customized service robot as determined by nursing students (as proxies for nursing staff in health care environments). This service robot, referred to as the Adaptive Robotic Nurse Assistant (ARNA), was developed to enhance the productivity of nurses through cooperation during physical tasks (eg, patient walking, item fetching, object delivery) as well as nonphysical tasks (eg, patient observation and feedback). This pilot study evaluated the acceptability of ARNA to provide ambulatory assistance to patients. METHODS: We conducted a trial with 24 participants to collect data and address the following research question: Is the use of ARNA as an ambulatory assistive device for patients acceptable to nurses? The experiments were conducted in a simulated hospital environment. Nursing students (as proxies for nursing staff) were grouped in dyads, with one participant serving as a nurse and the other acting as a patient. Two questionnaires were developed and administrated to the participants based on the Technology Acceptance Model with respect to the two subscales of perceived usefulness and perceived ease of use metrics. In order to evaluate the internal consistency/reliability of the questionnaires, we calculated Cronbach alpha coefficients. Furthermore, statistical analyses were conducted to evaluate the relation of each variable in the questionnaires with the overall perceived usefulness and perceived ease of use metrics. RESULTS: Both Cronbach alpha values were acceptably high (.93 and .82 for perceived usefulness and perceived ease of use questionnaires, respectively), indicating high internal consistency of the questionnaires. The correlation between the variables and the overall perceived usefulness and perceived ease of use metrics was moderate. The average perceived usefulness and perceived ease of use metrics among the participants were 4.13 and 5.42, respectively, out of possible score of 7, indicating a higher-than-average acceptability of this service robot. CONCLUSIONS: The results served to identify factors that could affect nurses' acceptance of ARNA and aspects needing improvement (eg, flexibility, ease of operation, and autonomy level).

Effectiveness of Second Wave COVID-19 Response Strategies in Australia

BackgroundThere is a significant challenge in responding to second waves of COVID-19 cases, with governments being hesitant in introducing hard lockdown measures given the resulting economic impact. In addition, rising case numbers reflect an increase in coronavirus transmission some time previously, so timing of response measures is highly important. Australia experienced a second wave from June 2020 onwards, confined to greater Melbourne, with initial social distancing measures failing to reduce rapidly increasing case numbers. We conducted a detailed analysis of this outbreak, together with an evaluation of the effectiveness of alternative response strategies, to provide guidance to countries experiencing second waves of SARS-Cov-2 transmission. MethodAn individual-based transmission model was used to 1) describe a second-wave COVID-19 epidemic in Australia; 2) evaluate the impact of lockdown strategies used; and 3) evaluate effectiveness of alternative mitigation strategies. The model was calibrated using daily diagnosed case data prior to lockdown. Specific social distancing interventions were modelled by adjusting person-to-person contacts in mixing locations. ResultsModelling earlier activation of lockdown measures are predicted to reduce total case numbers by more than 50%. Epidemic peaks and duration of the second wave were also shown to reduce. Our results suggest that activating lockdown measures when second-wave case numbers first indicated exponential growth, would have been highly effective in reducing COVID-19 cases. The model was shown to realistically predict the epidemic growth rate under the social distancing measures applied, validating the methods applied. ConclusionsThe timing of social distancing activation is shown to be critical to their effectiveness. Data showing exponential rise in cases, doubling every 7-10 days, can be used to trigger early lockdown measures. Such measures are shown to be necessary to reduce daily and total case numbers, and the consequential health burden, so preventing health care facilities being overwhelmed. Early control of second wave resurgence potentially permits strict lockdown measures to be eased earlier. All authors have seen and approved the manuscript. Research funding from Department of Health, Western Australia and Department of Health, Queensland is acknowledged. The authors confirm that these organisations had no influence on the submitted work, nor are there any competing interests.

Recognition of emotional facial expressions in adolescents with attention deficit/hyperactivity disorder.

INTRODUCTION: Attention Deficit/Hyperactivity Disorder (ADHD) is associated with impaired social competencies, due in part to an inability to determine emotional states through facial expressions. Social interactions are a critical component of adolescence, which raises the question of how do adolescents with ADHD cope with this impairment. Yet, previous reviews do not distinguish between children and adolescents. This review focuses on the ability of adolescents (defined by the World Health Organization as 10-19 years old) with ADHD to recognize emotional facial expressions, when compared to their typically-developing peers. METHODS: Comprehensive database search and analysis yielded 9 relevant studies published between 2008 and 2018. RESULTS: The studies reviewed here examined recognition of emotional facial expressions in adolescents with ADHD. Behavioral measures (reaction time, reaction time variance and recognition accuracy) show no statistically significant differences between adolescents with ADHD and their typically-developing peers. However, neural responses as recorded using functional Magnetic Resonance Imaging (fMRI) or Event Related Potentials (ERP) find differences in brain activity and the temporal evolution of the reaction between the two groups. CONCLUSIONS: Studies of children and of adults with ADHD find deficiencies in the recognition of emotional facial expressions. However, this review shows that adolescents with ADHD perform comparably to their peers on accuracy and rate, although their neural processing is different. This suggests that the methodologies employed by the ADHD and typically-developing adolescents to asses facial expressions are different. Further study is needed to determine what these may be.

Remote monitoring using donor-derived, cell-free DNA after kidney transplantation during the coronavirus disease 2019 pandemic

Background@#Donor-derived, cell-free DNA (dd-cfDNA) level correlates with allograft injury with clinical validity and utility for quiescence and active acute rejection (AR) in kidney transplant recipients. We analyzed trends in dd-cfDNA level immediately preceding and during the coronavirus disease 2019 (COVID-19) pandemic with implemented “shelter in place” and a tele-health strategy with remote home phlebotomy to limit COVID-19 exposure. @*Methods@#During COVID-19 in the United States (US), we surveyed weekly (January 6, 2020-May 25, 2020) metrics for dd-cfDNA corresponding to both a low risk for active rejection (dd-cfDNA 1.0%. During the study timeframe, over 11,000 patient samples (67%) from 150 kidney transplantation centers were transitioned from standard facility-based to remote phlebotomy. @*Results@#The proportion of dd-cfDNA samples, analyzed in 21 weekly aggregated cohorts by risk-stratification category, was unchanged during the COVID-19 escalation in the US. Linearized slopes for numbers of samples corresponding to indeterminate risk for AR cohorts of > 1.0% and 0.5% to 1.0% were -0.31 and -0.12, respectively; indicating that prevalence of these “at risk for AR cohorts” decreased during remote surveillance. Approximately 73% of samples corresponded to low risk of AR (dd-cfDNA < 0.5%), while an additional 15% of samples had dd-cfDNAlevel ≤ 1.0%. @*Conclusion@#The combination of remote home phlebotomy including dd-cfDNA analysis and a tele-health program offer a new paradigm that may substantially improve patient compliance and assuage anxiety regarding the state of kidney allograft health during the COVID-19 pandemic. Further prospective multi-center studies with robust outcomes data are warranted.

Remote monitoring using donor-derived, cell-free DNA after kidney transplantation during the coronavirus disease 2019 pandemic

Background@#Donor-derived, cell-free DNA (dd-cfDNA) level correlates with allograft injury with clinical validity and utility for quiescence and active acute rejection (AR) in kidney transplant recipients. We analyzed trends in dd-cfDNA level immediately preceding and during the coronavirus disease 2019 (COVID-19) pandemic with implemented “shelter in place” and a tele-health strategy with remote home phlebotomy to limit COVID-19 exposure. @*Methods@#During COVID-19 in the United States (US), we surveyed weekly (January 6, 2020-May 25, 2020) metrics for dd-cfDNA corresponding to both a low risk for active rejection (dd-cfDNA 1.0%. During the study timeframe, over 11,000 patient samples (67%) from 150 kidney transplantation centers were transitioned from standard facility-based to remote phlebotomy. @*Results@#The proportion of dd-cfDNA samples, analyzed in 21 weekly aggregated cohorts by risk-stratification category, was unchanged during the COVID-19 escalation in the US. Linearized slopes for numbers of samples corresponding to indeterminate risk for AR cohorts of > 1.0% and 0.5% to 1.0% were -0.31 and -0.12, respectively; indicating that prevalence of these “at risk for AR cohorts” decreased during remote surveillance. Approximately 73% of samples corresponded to low risk of AR (dd-cfDNA < 0.5%), while an additional 15% of samples had dd-cfDNAlevel ≤ 1.0%. @*Conclusion@#The combination of remote home phlebotomy including dd-cfDNA analysis and a tele-health program offer a new paradigm that may substantially improve patient compliance and assuage anxiety regarding the state of kidney allograft health during the COVID-19 pandemic. Further prospective multi-center studies with robust outcomes data are warranted.

Functional redundancy between RAP1 isoforms in murine platelet production and function.

RAP GTPases, important regulators of cellular adhesion, are abundant signaling molecules in the platelet/megakaryocytic lineage. However, mice lacking the predominant isoform, RAP1B, display a partial platelet integrin activation defect and have a normal platelet count, suggesting the existence of a RAP1-independent pathway to integrin activation in platelets and a negligible role for RAP GTPases in megakaryocyte biology. To determine the importance of individual RAP isoforms on platelet production and on platelet activation at sites of mechanical injury or vascular leakage, we generated mice with megakaryocyte-specific deletion (mKO) of Rap1a and/or Rap1b Interestingly, Rap1a/b-mKO mice displayed a marked macrothrombocytopenia due to impaired proplatelet formation by megakaryocytes. In platelets, RAP isoforms had redundant and isoform-specific functions. Deletion of RAP1B, but not RAP1A, significantly reduced α-granule secretion and activation of the cytoskeleton regulator RAC1. Both isoforms significantly contributed to thromboxane A2 generation and the inside-out activation of platelet integrins. Combined deficiency of RAP1A and RAP1B markedly impaired platelet aggregation, spreading, and clot retraction. Consistently, thrombus formation in physiological flow conditions was abolished in Rap1a/b-mKO, but not Rap1a-mKO or Rap1b-mKO, platelets. Rap1a/b-mKO mice were strongly protected from experimental thrombosis and exhibited a severe defect in hemostasis after mechanical injury. Surprisingly, Rap1a/b-mKO platelets were indistinguishable from controls in their ability to prevent blood-lymphatic mixing during development and hemorrhage at sites of inflammation. In summary, our studies demonstrate an essential role for RAP1 signaling in platelet integrin activation and a critical role in platelet production. Although important for hemostatic/thrombotic plug formation, platelet RAP1 signaling is dispensable for vascular integrity during development and inflammation.

Soil Microbiomes Associated with Verticillium Wilt-Suppressive Broccoli and Chitin Amendments are Enriched with Potential Biocontrol Agents.

Two naturally infested Verticillium wilt-conducive soils from the Salinas Valley of coastal California were amended with disease-suppressive broccoli residue or crab meal amendments, and changes to the soil prokaryote community were monitored using Illumina sequencing of a 16S ribosomal RNA gene library generated from 160 bulk soil samples. The experiment was run in a greenhouse, twice, with eggplant as the Verticillium wilt-susceptible host. Disease suppression, plant height, soil microsclerotia density, and soil chitinase activity were assessed at the conclusion of each experiment. In soil with high microsclerotia density, all amendments significantly reduced Verticillium wilt severity and microsclerotia density, and increased soil chitinase activity. Plant height was increased only in the broccoli-containing treatments. In total, 8,790 error-corrected sequence variants representing 1,917,893 different sequences were included in the analyses. The treatments had a significant impact on the soil microbiome community structure but measures of α diversity did not vary between treatments. Community structure correlated with disease score, plant height, microsclerotia density, and soil chitinase activity, suggesting that the prokaryote community may affect the disease-related response variables or vice versa. Similarly, the abundance of 107 sequence variants correlated with disease-related response variables, which included variants from genera with known antagonists of filamentous fungal plant pathogens, such as Pseudomonas and Streptomyces. Overall, genera with antifungal antagonists were more abundant in amended soils than unamended soils, and constituted up to 8.9% of all sequences in broccoli+crabmeal-amended soil. This study demonstrates that substrate-mediated shifts in soil prokaryote communities are associated with the transition of Verticillium wilt-conducive soils to Verticillium wilt-suppressive soils, and suggests that soils likely harbor numerous additional antagonists of fungal plant pathogens that contribute to the biological suppression of plant disease.

Immunotherapy for acute myeloid leukemia (AML): a potent alternative therapy.

The standard therapy of AML for many years has been chemotherapy with or without stem transplantation. However, there has not been any tangible improvement in this treatment beyond induction through chemotherapy and consolidation with allogeneic stem cell transplantation or chemotherapy. Residual AML cells which later cause relapse mostly persist even after rigorous standard therapy. It is imperative therefore to find an alternative therapy that can take care of the residual AML cells. With a better understanding of how the immune system works to destroy tumor cells and inhibit their growth, another therapeutic option immunotherapy has emerged to address the difficulties associated with the standard therapy. Identification of leukemia-associated antigens (LAA) and the fact that T and NK cells can be activated to exert cytotoxicity on AML cells have further introduced diverse immunotherapeutic development strategies. This review discusses the merits of current immunotherapeutic strategies such as the use of antibodies, adoptive T cells and alloreactive NK cell, and vaccination as against the standard therapy of AML.

miRNA Enriched in Human Neuroblast Nuclei Bind the MAZ Transcription Factor and Their Precursors Contain the MAZ Consensus Motif.

While the cytoplasmic function of microRNA (miRNA) as post-transcriptional regulators of mRNA has been the subject of significant research effort, their activity in the nucleus is less well characterized. Here we use a human neuronal cell model to show that some mature miRNA are preferentially enriched in the nucleus. These molecules were predominantly primate-specific and contained a sequence motif with homology to the consensus MAZ transcription factor binding element. Precursor miRNA containing this motif were shown to have affinity for MAZ protein in nuclear extract. We then used Ago1/2 RIP-Seq to explore nuclear miRNA-associated mRNA targets. Interestingly, the genes for Ago2-associated transcripts were also significantly enriched with MAZ binding sites and neural function, whereas Ago1-transcripts were associated with general metabolic processes and localized with SC35 spliceosomes. These findings suggest the MAZ transcription factor is associated with miRNA in the nucleus and may influence the regulation of neuronal development through Ago2-associated miRNA induced silencing complexes. The MAZ transcription factor may therefore be important for organizing higher order integration of transcriptional and post-transcriptional processes in primate neurons.