Deciphering the role of miRNA in reprogramming plant responses to drought stress.

Drought is the most prevalent environmental stress that affects plants' growth, development, and crop productivity. However, plants have evolved adaptive mechanisms to respond to the harmful effects of drought. They reprogram their: transcriptome, proteome, and metabolome that alter their cellular and physiological processes and establish cellular homeostasis. One of the crucial regulatory processes that govern this reprogramming is post-transcriptional regulation by microRNAs (miRNAs). miRNAs are small non-coding RNAs, involved in the downregulation of the target mRNA via translation inhibition/mRNA degradation/miRNA-mediated mRNA decay/ribosome drop off/DNA methylation. Many drought-inducible miRNAs have been identified and characterized in plants. Their main targets are regulatory genes that influence growth, development, osmotic stress tolerance, antioxidant defense, phytohormone-mediated signaling, and delayed senescence during drought stress. Overexpression of drought-responsive miRNAs (Osa-miR535, miR160, miR408, Osa-miR393, Osa-miR319, and Gma-miR394) in certain plants has led to tolerance against drought stress indicating their vital role in stress mitigation. Similarly, knock down (miR166/miR398c) or deletion (miR169 and miR827) of miRNAs has also resulted in tolerance to drought stress. Likewise, engineered Arabidopsis plants with miR165, miR166 using short tandem target mimic strategy, exhibited drought tolerance. Since miRNAs regulate the expression of an array of drought-responsive genes, they can act as prospective targets for genetic manipulations to enhance drought tolerance in crops and achieve sustainable agriculture. Further investigations toward functional characterization of diverse miRNAs, and understanding stress-responses regulated by these miRNAs and their utilization in biotechnological applications is highly recommended.

Post-traumatic stress disorder and its associated factors among survivors of 2015 earthquake in Nepal.

BACKGROUND: Natural disasters cause long term psychological consequences, especially post-traumatic stress disorders. It has been regarded as the most prevalent of psychiatric disorders after a natural disaster. The purpose of this study is to estimate the prevalence of Post-Traumatic Stress Disorder (PTSD) and determine its associated factors in adult survivors three years after the 2015 Nepal earthquake. METHODS: A cross-sectional descriptive design was used where 1076 adults within the age range of 19-65 were randomly selected and interviewed from four adversely affected districts due to the 2015 earthquake. Instruments included a demographic questionnaire, an earthquake exposure questionnaire, the Oslo Social Support Scale (OSSS), and the Post-traumatic Stress Disorder Checklist-Civilian Version (PCL-C). Descriptive and inferential statistics were applied using Statistical Package for Social Science (SPSS) Version 16 for data analysis. RESULTS: The prevalence of PTSD among earthquake survivors was 18.9%. The multivariate logistic regression showed that gender, ethnicity, education, occupation, social support and severity of damage to house and property were significantly associated with PTSD. Odds of having PTSD was 1.6 times higher among females (AOR = 1.6, 95% CI: 1.1-2.3) and nearly 2 times higher amongst illiterate survivors (AOR = 1.9, 95% CI: 1.2-2.8). Participants from the Janajati ethnic group and those who had a business occupation had a 50% lower risk of having PTSD. Around 39% of the participants had moderate social support and had 60% lower odds of having PTSD compared to those with poor social support (AOR = 0.4, 95%CI: 0.2-0.5, p < 0.001). Participants with medium and very high-level damage to personal property were more likely to have PTSD. CONCLUSION: Post-traumatic stress disorder remained prevalent amongst survivors three years after the 2015 Nepal Earthquake. It is important to provide psychological and social support for survivors to decrease the health burden from PTSD. Socio-demographic characteristics such as females, farmers, those survivors who endured significant personal property damage were at higher risk.

Silicon nanoparticles: Synthesis, uptake and their role in mitigation of biotic stress.

In the current scenario of global warming and climate change, plants face many biotic stresses, which restrain growth, development and productivity. Nanotechnology is gaining precedence over other means to deal with biotic and abiotic constraints for sustainable agriculture. One of nature's most beneficial metalloids, silicon (Si) shows ameliorative effect against environmental challenges. Silicon/Silica nanoparticles (Si/SiO2NPs) have gained special attention due to their significant chemical and optoelectronic capabilities. Its mesoporous nature, easy availability and least biological toxicity has made it very attractive to researchers. Si/SiO2NPs can be synthesised by chemical, physical and biological methods and supplied to plants by foliar, soil, or seed priming. Upon uptake and translocation, Si/SiO2NPs reach their destined cells and cause optimum growth, development and tolerance against environmental stresses as well as pest attack and pathogen infection. Using Si/SiO2NPs as a supplement can be an eco-friendly and cost-effective option for sustainable agriculture as they facilitate the delivery of nutrients, assist plants to mitigate biotic stress and enhances plant resistance. This review aims to present an overview of the methods of formulation of Si/SiO2NPs, their application, uptake, translocation and emphasize the role of Si/SiO2NPs in boosting growth and development of plants as well as their conventional advantage as fertilizers with special consideration on their mitigating effects towards biotic stress.

Development of a clickable designer monolignol for interrogation of lignification in plant cell walls.

Lignin is an abundant and essential polymer in land plants. It is a prime factor in the recalcitrance of lignocellulosic biomass to agricultural and industrial end-uses such as forage, pulp and papermaking, and biofuels. To better understand lignification at the molecular level, we are developing a lignin spectroscopic and imaging toolbox on one "negligible" auxiliary. Toward that end, we describe the design, synthesis, and characterization of a new designer monolignol, 3-O-propargylcaffeyl alcohol, which contains a bioorthogonal alkynyl functional group at the 3-O-position. Importantly, our data indicate that this monolignol does not alter the fidelity of lignification. We demonstrate that the designer monolignol provides a platform for multiple spectroscopic and imaging approaches to reveal temporal and spatial details of lignification, the knowledge of which is critical to reap the potential of energy-rich renewable plant biomass for sustainable liquid fuels and other diverse economic applications.

Growing Medical Educators from Medical Students by Supporting Self-directing Learning Opportunities Born Out of Cadaveric Dissection.

This study focuses on a subset of medical students who participated in an anatomy dissection program and undertook an additional self-directed learning (SDL) project investigating incidental findings of cadaveric pathology. The value of SDL activity is explored as a means of enhancing medical student education, particularly its student perceived value in preparing and developing them as future medical educators. It was assessed whether the project advanced student interest in medical education by analyzing their motivations for participation. The results of the study highlight the potential of SDL as an experiential learning opportunity for medical students and the role of anatomic pathology in connecting multiple domains of medical education.

A Comprehensive Analysis of Calmodulin-Like Proteins of Glycine max Indicates Their Role in Calcium Signaling and Plant Defense Against Insect Attack.

The calcium (Ca2+) signaling is a crucial event during plant-herbivore interaction, which involves a transient change in cytosolic Ca2+ concentration, which is sensed by Ca2+-sensors, and the received message is transduced to downstream target proteins leading to appropriate defense response. Calmodulin-like proteins (CMLs) are calcium-sensing plant-specific proteins. Although CMLs have been identified in a few plants, they remained uncharacterized in leguminous crop plants. Therefore, a wide-range analysis of CMLs of soybean was performed, which identified 41 true CMLs with greater than 50% similarity with Arabidopsis CMLs. The phylogenetic study revealed their evolutionary relatedness with known CMLs. Further, the identification of conserved motifs, gene structure analysis, and identification of cis-acting elements strongly supported their identity as members of this family and their involvement in stress responses. Only a few Glycine max CMLs (GmCMLs) exhibited differential expression in different tissue types, and rest of them had minimal expression. Additionally, differential expression patterns of GmCMLs were observed during Spodoptera litura-feeding, wounding, and signaling compound treatments, indicating their role in plant defense. The three-dimensional structure prediction, identification of interactive domains, and docking with Ca2+ ions of S. litura-inducible GmCMLs, indicated their identity as calcium sensors. This study on the characterization of GmCMLs provided insights into their roles in calcium signaling and plant defense during herbivory.

Educational Case: Understanding Kwashiorkor and Marasmus: Disease Mechanisms and Pathologic Consequences.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, seehttp://journals.sagepub.com/doi/10.1177/2374289517715040.1.

'Remediation of pre-clerkship clinical skill performance using a hybrid coaching model'.

SUBSTANCE: We reviewed the effect of a hybrid remediation model combining co-regulated learning and deliberate practice on future exam performance of pre-clerkship medical students who had been unsuccessful on a previous clinic skills exam. With this remediation model, we aimed to strengthen students' self-regulated learning to improve future exam performance and support sustained and improved learning. Educational problem addressed: Observing that some students who initially performed well post remediation with deliberate practice, still struggled on future exams, we looked to address a method that could improve both short-and long-term clinical skills learning success with sustained performance. Intervention outcome: Comparing the remediated students' exam scores pre- and post-coaching to their cohort's performance, we observed the majority of students post remediation performed above their cohort's exam average. Lessons learned: Combining learning models resulted in improved learning outcomes.

Educational Case: Bladder Urothelial Cell Carcinoma TNM Stage, Prognosis and Management.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040. 1.

Role of nanoparticles in crop improvement and abiotic stress management.

Nanoparticles (NPs) possess specific physical and chemical features and they are capable enough to cross cellular barriers and show their effect on living organisms. Their capability to cross cellular barriers have been noticed for their application not only in medicine, electronics, chemical and physical sciences, but also in agriculture. In agriculture, nanotechnology can help to improve the growth and crop productivity by the use of various nanoscale products such as nanofertilizers, nanoherbicides, nanofungicides, nanopesticides etc. An optimized concentration of NPs can be administered by incubation of seeds, roots, pollen, isolated cells and protoplast, foliar spraying, irrigation with NPs, direct injection, hydroponic treatment and delivery by biolistics. Once NPs come in contact with plant cells, they are uptaken by plasmodesmatal or endocytosed pathways and translocated via apoplastic and / symplastic routes. Once beneficial NPs reach different parts of plants, they boost photosynthetic rate, biomass measure, chlorophyll content, sugar level, buildup of osmolytes and antioxidants. NPs also improve nitrogen metabolism, enhance chlorophyll as well as protein content and upregulate the expression of abiotic- and biotic stress-related genes. Herein, we review the state of art of different modes of application, uptake, transport and prospective beneficial role of NPs in stress management and crop improvement.

RGS6 Mediates Effects of Voluntary Running on Adult Hippocampal Neurogenesis.

Voluntary running enhances adult hippocampal neurogenesis, with consequences for hippocampal-dependent learning ability and mood regulation. However, the underlying mechanism remains unclear. Here, we show that voluntary running induces unique and dynamic gene expression changes specifically within the adult-born hippocampal neurons, with significant impact on genes involved in neuronal maturation and human diseases. We identify the regulator of G protein signaling 6 (RGS6) as a key factor that mediates running impact on adult-born neurons. RGS6 overexpression mimics the positive effects of voluntary running on morphological and physiological maturation of adult new neurons and reduced sensitivity of adult-born neurons to the inhibitory effect of GABAB (γ-Aminobutyric acid B) receptor activation. Knocking down RGS6 abolishes running-enhanced neuronal maturation and hippocampal neurogenesis-dependent learning and anxiolytic effect. Our study provides a data resource showing genome-wide intrinsic molecular changes in adult-born hippocampal neurons that contribute to voluntary running-induced neurogenesis.

Modulation of tumor induction and progression of oncogenic K-ras-positive tumors in the presence of TGF- b1 haploinsufficiency.

Oncogenic K-ras is one of the most common genetic alterations in human lung adenocarcinomas. In addition, inactivation of clusters of tumor suppressor genes is required to bring about classical characteristics of cancer including angiogenesis as a prelude to invasion and metastasis. Transforming growth factor-beta (TGF-beta) 1 is a tumor suppressor gene that is implicated in lung cancer progression. Although in vitro studies have shown that TGF-beta1 and Ras pathways cooperate during tumorigenesis, the biology of interaction of TGF-beta1 and Ras has not been studied in in vivo tumorigenesis. We hypothesized that inactivation of TGF-beta1 in addition to oncogeneic activation of K-ras would lead to early initiation and faster progression to lung adenocarcinoma and invasion and metastasis. Heterozygous (HT) TGF-beta1 mice were mated with latent activatable (LA) mutated K-ras mice to generate TGF-beta1(+/+), K-ras LA (wild-type (WT)/LA) and TGF-beta1(+/-), K-ras LA (HT/LA) mice. Both HT/LA and WT/LA mice developed spontaneous lung tumors, but HT/LA mice progressed to adenocarcinomas significantly earlier compared with WT/LA mice. In addition, WT/LA adenocarcinomas had significantly higher angiogenic activity compared with HT/LA adenocarcinomas. Thus, while oncogenic K-ras mutation and insensitivity to the growth regulatory effects of TGF-beta1 is essential for initiation and progression of mouse lung tumors to adenocarcinoma, a full gene dosage of TGF-beta1 is required for tumor-induced angiogenesis and invasive potential. This study identifies a number of genes not previously associated with lung cancer that are involved in tumor induction and progression. In addition, we provide evidence that progression to invasive angiogenic lesions requires TGF-beta1 responsiveness in addition to Ras mutation.

Investigating Biochemical and Developmental Dependencies of Lignification with a Click-Compatible Monolignol Analog in Arabidopsis thaliana Stems.

Lignin is a key structural component of plant cell walls that provides rigidity, strength, and resistance against microbial attacks. This hydrophobic polymer also serves a crucial role in water transport. Despite its abundance and essential functions, several aspects of lignin biosynthesis and deposition remain cryptic. Lignin precursors are known to be synthesized in the cytoplasm by complex biosynthetic pathways, after which they are transported to the apoplastic space, where they are polymerized via free radical coupling reactions into polymeric lignin. However, the lignin deposition process and the factors controlling it are unclear. In this study, the biochemical and developmental dependencies of lignification were investigated using a click-compatible monolignol analog, 3-O-propargylcaffeyl alcohol (3-OPC), which can incorporate into both in vitro polymerized lignin and Arabidopsis thaliana tissues. Fluorescence labeling of 3-OPC using click chemistry followed by confocal fluorescence microscopy enabled the detection and imaging of 3-OPC incorporation patterns. These patterns were consistent with endogenous lignification observed in different developmental stages of Arabidopsis stems. However, the concentration of supplied monolignols influenced where lignification occurred at the subcellular level, with low concentrations being deposited in cell corners and middle lamellae and high concentrations also being deposited in secondary walls. Experimental inhibition of multiple lignification factors confirmed that 3-OPC incorporation proceeds via a free radical coupling mechanism involving peroxidases/laccases and reactive oxygen species (ROS). Finally, the presence of peroxide-producing enzymes determined which cell walls lignified: adding exogenous peroxide and peroxidase caused cells that do not naturally lignify in Arabidopsis stems to lignify. In summary, 3-OPC accurately mimics natural lignification patterns in different developmental stages of Arabidopsis stems and allows for the dissection of key biochemical and enzymatic factors controlling lignification.

A versatile click-compatible monolignol probe to study lignin deposition in plant cell walls.

Lignin plays important structural and functional roles in plants by forming a hydrophobic matrix in secondary cell walls that enhances mechanical strength and resists microbial decay. While the importance of the lignin matrix is well documented and the biosynthetic pathways for monolignols are known, the process by which lignin precursors or monolignols are transported and polymerized to form this matrix remains a subject of considerable debate. In this study, we have synthesized and tested an analog of coniferyl alcohol that has been modified to contain an ethynyl group at the C-3 position. This modification enables fluorescent tagging and imaging of this molecule after its incorporation into plant tissue by click chemistry-assisted covalent labeling with a fluorescent azide dye, and confers a distinct Raman signature that could be used for Raman imaging. We found that this monolignol analog is incorporated into in vitro-polymerized dehydrogenation polymer (DHP) lignin and into root epidermal cell walls of 4-day-old Arabidopsis seedlings. Incorporation of the analog in stem sections of 6-week-old Arabidopsis thaliana plants and labeling with an Alexa-594 azide dye revealed the precise locations of new lignin polymerization. Results from this study indicate that this molecule can provide high-resolution localization of lignification during plant cell wall maturation and lignin matrix assembly.

Angiogenesis and capillary maturation phenotypes associated with the Edpm3 locus on rat chromosome 3.

The quantitative trait locus (QTL) Edpm3 is one of a group of additively acting QTL \responsible for the difference in estrogen-induced pituitary tumor growth between the tumor-susceptible F344 and tumor-resistant BN rat strains. The F344.BN-Edpm3(BN) rat strain was produced by moving the segment of rat Chr 3 between D3Mgh7 and D3Mgh13, which contains the Edpm3 QTL, from the BN strain into the F344 genetic background. In a previous study, we used this congenic line to find that the BN allele of the Edpm3 QTL reduces tissue mass and S-phase fraction in the estrogen-induced rat pituitary tumor. We now report on the use of this congenic line to investigate the linkage of Edpm3 to tumor angiogenesis. Contrary to expectation, the F344.BN-Edpm3(BN) strain has significantly greater angiogenic activity than does F344 in both treated and untreated rats. Microvessel count (MVC), perivascular space, and number of nonattached pericytes/pericapillary fibroblasts are all elevated in the pituitary by chronic estrogen treatment and their values are significantly greater in F344.BN-Edpm3(BN) than F344. Thus, although there is greater angiogenic activity in the pituitary of estrogen-treated F344.BN-Edpm3(BN) rats, there is a deficiency in capillary maturation compared with F344.

Localization of Eutr2, a locus controlling susceptibility to DES-induced uterine inflammation and pyometritis, to RNO5 using a congenic rat strain.

In some rat strains chronic administration of exogenous estrogens induces pyometritis, an inflammation of the uterus associated with infection, suggesting that there is genetic variation in susceptibility to estrogen-induced inflammation and pyometritis. In this article we report that following 10 weeks of treatment with the synthetic estrogen diethylstilbestrol (DES), Fisher 344 (F344) rats exhibit modest uterine inflammation and a 0% incidence of pyometritis. By contrast, under identical experimental conditions, Brown Norway (BN) rats exhibit significant inflammation and a 100% incidence of pyometritis. Similarly, we also observed profound uterine inflammation and a 100% incidence of pyometritis in a congenic rat strain in which a segment of RNO5 from the BN strain is carried on the F344 strain. These data suggest that a locus on RNO5 controls both the magnitude of DES-induced uterine inflammation and susceptibility to DES-induced pyometritis. This locus, designated Eutr2, resides within the same segment of RNO5 as the Eutr1 locus, which confers susceptibility to E2-induced pyometritis in an F2 population generated in a cross between the BN and August x Copenhagen 9935, Irish (ACI) strains.