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Brassinosteroids as Central Regulators of Plant Growth, Stress Tolerance, and Agricultural Resilience.

Brassinosteroids (BRs) are essential steroidal phytohormones that regulate plant growth, development, and responses to environmental stresses. Recent studies have demonstrated the important roles of BRs in enhancing plant tolerance to abiotic stresses, including drought, salinity, temperature extremes, heavy metal toxicity, and oxidative stress, as well as biotic stresses caused by pathogens and herbivores. This review summarizes current advances in BR biosynthesis, metabolism, transport, and signaling pathways, focusing on key components that mediate stress adaptation. We discuss the physiological and molecular mechanisms through which BRs improve stress tolerance, including regulation of antioxidant defense, ion homeostasis, osmotic adjustment, and stress-responsive gene expression. Particular attention is given to the extensive cross talk between BRs and other phytohormones, such as abscisic acid, jasmonic acid, salicylic acid, ethylene, auxin, and gibberellins, which enables plants to balance growth and defense under adverse conditions. Furthermore, we highlighted the potential applications of BRs in crop improvement through exogenous treatments, genetic engineering, and genome-editing approaches. However, the effectiveness of BR-based strategies is highly dependent on crop species, developmental stage, stress type, BR concentration, application method, and environmental conditions. In addition, excessive BR accumulation or application may result in undesirable growth responses, and further multi-location field validation is required before widespread agricultural implementation. Finally, we discuss emerging research trends, current knowledge gaps, and future perspectives for exploring BR signaling to develop climate-resilient crops. Overall, BRs represent promising targets for improving crop stress resilience; however, optimizing BR-mediated strategies and validating their long-term performance under diverse field conditions will be essential for their successful application in sustainable agriculture.

abiotic stress↗

The Royal College of Surgeons 19th-century textbook of paediatrics and its authors Evanson and Maunsell.

Richard T. Evanson, Professor of Medicine in the RCSI and Henry Maunsell, Professor of Obstetrics, jointly published a textbook of paediatrics which went through five editions between 1836 and 1847. The textbook was based on their practical experience in the treatment of children in the Institution of the Diseases, founded in 1821. This was probably the first Children's Hospital in these islands. The textbook reviews neonatal care, normal development, and the diagnosis and treatment of childhood illnesses. It was well received at home and abroad and it was a major contribution to contemporary literature.

History, 19th Century↗

Improved detection of depression in primary care through severity evaluation.

OBJECTIVES: To determine whether the use of a symptom severity measure to augment an existing Diagnostic and Statistical Manual of Mental Disorders-Third Edition, Revised (DSM-III-R) criteria-based depression screener (PRIME-MD) would decrease the difficulties associated with depression screening in primary care by filtering out patients with minimal impairment. STUDY DESIGN: The study design was secondary data analysis. POPULATION: The study sample comprised 1317 patients, with intentional oversampling by ethnicity and sex, presenting for routine care at a university family practice center in Galveston, Texas. OUTCOMES MEASURED: The primary outcomes were cross-sectional, health-related quality-of-life outcomes of subjects who met symptom severity criteria as well as criteria for a DSM-III-R mood disorder. Health care utilization outcomes were examined as secondary outcomes. RESULTS: The combination of a 6-item depression severity instrument and the PRIME-MD resulted in 71% of depressed subjects being categorized as severely symptomatic and 29% as minimally symptomatic. Severely symptomatic subjects had significantly worse SF-36 Mental Health Component Summary scale (MCS) scores than did minimally symptomatic subjects (32.8 vs 43.5, P <.05). Minimally symptomatic subjects had MCS scores similar to those of a third group of subjects who did not meet DSM-III-R "threshold" criteria for mood disorder but who were severely symptomatic. Adjusted health care utilization was higher for the initial 3-month charge period in the severely symptomatic depressed subjects compared with minimally symptomatic depressed subjects ($679.20 vs $462.38, P <.05). CONCLUSIONS: The 6-item depression severity measure effectively separated patients meeting DSM-III-R "threshold" depression criteria into 2 groups: one presenting with severe symptoms and impairment and the other presenting with mild symptoms and significantly less impairment. A strategy of initial screening using a brief depression severity instrument, followed with a DSM criteria-based instrument, could decrease the immediate clinician workload by one third and focus treatment on those most likely to benefit.

Adult↗

Purification and characterization of double-stranded RNA adenosine deaminase from bovine nuclear extracts.

The double-stranded RNA (dsRNA) adenosine deaminase (DRADA) deaminates adenosine residues to inosines and creates I-U mismatched base pairs in dsRNAs. Its involvement in RNA editing of glutamate-gated ion channel gene transcripts in mammalian brains has been proposed as one of the biological functions for this recently identified cellular enzyme. We purified a mixture of three forms, 93, 88, and 83 kDa, of bovine DRADA proteins, all likely to be active enzymes. We determined that DRADA has a native molecular mass of approximately 100 kDa, suggesting that the enzyme exists as a monomer. The purified enzyme was not inhibited by 2'-deoxycoformycin, a transition state analog inhibitor of adenosine deaminase and AMP deaminase, suggesting that the catalytic mechanism of DRADA might be different from that of other deaminases. DRADA binds specifically to dsRNA with a dissociation constant of 0.23 nM for a synthetic dsRNA, and the Michaelis constant is 0.85 nM. These values indicate that DRADA has a much higher affinity for its substrate than other deaminases such as adenosine deaminase and AMP deaminase. DRADA may need this extremely high affinity to catalyze efficiently the modification of relatively rare substrate RNAs in the cell nucleus.

Adenosine Deaminase↗

A computer program to aid in calculating similarity indexes from DNA fingerprints.

DNA SIMDEX is a DOS-based computer program designed to assist in the visual scoring of DNA fingerprint assays. DNA SIMDEX uses the migration distances of the individual DNA bands to generate lists of probable matching and nonmatching bands and automatically calculates a probable similarity index between DNA fingerprints based on these initial predictions. After comparisons are edited by the user, the final similarity index, along with accompanying data, can be saved on a floppy disk or hard drive for easy storage and retrieval or can be printed directly on a laser or line printer. The program has been developed to function with or without an image-analysis system, thus making it an inexpensive alternative for small laboratories.

DNA Fingerprinting↗

Comorbid migraine is associated with a negative impact on quality of life in patients with major depression.

This study investigated the impact of migraine on health-related quality of life (HRQoL) among patients with major depressive disorder (MDD). We prospectively enrolled 151 consecutive psychiatric out-patients meeting DSM-IV criteria for MDD. Migraine and other headache types were diagnosed based on the International Classification of Headache Disorders, 2nd edition (2004). The Short Form-36 (SF-36) was administered as a generic instrument of HRQoL. Among 151 patients with MDD, migraine (N = 73, 48.3%) was very common. Comorbidity of migraine predicted a significantly negative impact on all physical subscales and vitality but not on the other mental subscales of the SF-36 after controlling for depression, age and gender. The presence of migraine should be considered as an important physical symptom in clinic-based MDD samples. Simultaneous management of depression and severe headaches, especially migraine, might improve HRQoL in patients with MDD.

Adolescent↗

RNA editing: how a message is changed.

Considerable progress has been made in unraveling the mechanistic features of RNA editing processes in a number of genetic systems. Recent highlights include the identification of the catalytic subunit of the mammalian apolipoprotein B mRNA editing enzyme as a zinc-dependent cytidine deaminase that binds to RNA, the demonstration that adenosines in brain glutamate receptor pre-mRNAs are converted into inosines and that double-stranded RNA A deaminase (dsRAD), the candidate enzyme, is another zinc-dependent RNA nucleotide deaminase, and a mounting body of evidence for a cleavage-ligation mechanism for U insertion/deletion editing in kinetoplastid protozoa.

Animals↗

KISS: the kinetoplastid RNA editing sequence search tool.

Kinetoplastid mitochondrial mRNA editing is a post-transcriptional process of uridine insertion and deletion. Editing is mediated by small RNA molecules termed guide RNAs (gRNAs). Most gRNAs are encoded by numerous small circular DNA minicircles, while the protein coding mitochondrial genes are encoded on a separate, larger genome called the maxicircle. In order to provide a workbench for the analysis of RNA editing in kinetoplastids and a well-annotated set of guide RNAs for Trypanosoma brucei, we generated the kinetoplastid RNA editing sequence search tool (KISS) (http://gmod.mbl.edu/kiss/). KISS is a pipeline and database that uses BLAST comparisons and minicircle sequence motifs to annotate potential gRNAs and cognate mRNA editing sequence. KISS 1.0 contains all previously known minicircle and maxicircle data from Trypanosoma brucei plus >400 new minicircle sequences. Using an online format, KISS 1.0 allows the mapping and visualization of all known T. brucei gRNAs to minicircle genes and to potential mRNA substrates for RNA editing.

Animals↗

[RNA-editing: genetic information is corrected after transcription].

RNA editing (posttranscriptional alterations to messenger RNAs) is revealed in different genetic systems, primarily, in mitochondria and chloroplasts. In this review, we discuss the prevalence of the process, characteristic features in different taxonomic groups, specificity, biological implication, and possible evolutionary origin of this process. This is the first review of RNA editing in Russian.

Amino Acid Sequence↗

A bioinformatic screen for novel A-I RNA editing sites reveals recoding editing in BC10.

MOTIVATION: Recent studies have demonstrated widespread adenosine-inosine RNA editing in non-coding sequence. However, the extent of editing in coding sequences has remained unknown. For many of the known sites, editing can be observed in multiple species and often occurs in well-conserved sequences. In addition, they often occur within imperfect inverted repeats and in clusters. Here we present a bioinformatic approach to identify novel sites based on these shared features. Mismatches between genomic and expressed sequences were filtered to remove the main sources of false positives, and then prioritized based on these features. This protocol is tailored to identifying specific recoding editing sites, rather than sites in non-coding repeat sequences. RESULTS: Our protocol is more sensitive for identifying known coding editing sites than any previously published mammalian screen. A novel multiply edited transcript, BC10, was identified and experimentally verified. BC10 is highly conserved across a range of metazoa and has been implicated in two forms of cancer.

Adenosine↗

Developmental regulation of the translational repressor NAT1 during cardiac development.

The process of translation initiation has been postulated to play an important role in the regulation of cellular growth and proliferation. Here, we report the identification and differential expression of a fundamental translational repressor NAT1, during early postnatal cardiac development. Differential display analysis of RNA obtained from 3-day and 4-week-old rat hearts resulted in the cloning and identification of a 396 bp cDNA fragment (DRCF-6) which corresponded to the 3' terminal portion of NAT1. Northern blot analysis revealed that the mRNA expression of NAT1 was markedly elevated during the first 2 weeks of postnatal life, with an apparent peak level of expression occurring at 1 week. NAT1 mRNA levels then steadily decreased to 4 weeks of age. The NAT1 transcript has previously been shown to be extensively edited by the enzyme APOBEC-1, which deaminates specific cytidine bases to uridine; cytidine deamination at a glutamine codon (CAA) results in the formation of a stop codon (UAA) and consequently, premature termination of translation. Accordingly, Western blot analysis detected the presence of several smaller proteins in addition to the full length NAT1 protein (97 kDa), each exhibiting a distinct pattern of expression during cardiac development. APOBEC-1 editing of NAT1 during cardiac development was further supported by primer extension analysis of cytidine 1699, which was found to be predominantly edited to uridine. Immunohistochemical staining showed that NAT1 is expressed predominantly in atrial and ventricular myocytes, although staining was also detected in vascular smooth muscle cells and in the endocardium. These results suggest that NAT1 may play a role in the postnatal development of the heart and demonstrate that APOBEC-1 editing may possibly be a novel mechanism by which translation is regulated during cardiac development.

Aging↗

The structure of a yeast RNA-editing deaminase provides insight into the fold and function of activation-induced deaminase and APOBEC-1.

Activation-induced deaminase (AID) uses base deamination for class-switch recombination and somatic hypermutation and is related to the mammalian RNA-editing enzyme apolipoprotein B editing catalytic subunit 1 (APOBEC-1). CDD1 is a yeast ortholog of APOBEC-1 that exhibits cytidine deaminase and RNA-editing activity. Here, we present the crystal structure of CDD1 at 2.0-A resolution and its use in comparative modeling of APOBEC-1 and AID. The models explain dimerization and the need for trans-acting loops that contribute to active site formation. Substrate selectivity appears to be regulated by a central active site "flap" whose size and flexibility accommodate large substrates in contrast to deaminases of pyrimidine metabolism that bind only small nucleosides or free bases. Most importantly, the results suggested both AID and APOBEC-1 are equally likely to bind single-stranded DNA or RNA, which has implications for the identification of natural AID targets.

APOBEC-1 Deaminase↗

The crystal structure of leucyl-tRNA synthetase complexed with tRNALeu in the post-transfer-editing conformation.

Leucyl-tRNA synthetase (LeuRS) has a specific post-transfer editing activity directed against mischarged isoleucine and similar noncognate amino acids. We describe the post-transfer-editing and product complexes of Thermus thermophilus LeuRS (LeuRSTT) with tRNA(Leu) at 2.9- to 3.3-A resolution. In the post-transfer-editing configuration, A76 binds in the editing active site exactly as previously found for the adenosine moiety of a small-molecule editing-substrate analog. The 60 C-terminal residues of LeuRSTT, unseen in previous structures, fold into a compact domain flexibly linked to the rest of the molecule and interacting with the G19-C56 tertiary base pair of tRNA(Leu). LeuRS recognition of tRNA(Leu) depends essentially on tRNA shape rather than base-specific interactions. The structures show that considerable domain rotations, notably of the editing domain, accompany the tRNA-3' end dynamics associated successively with aminoacylation, post-transfer editing and product release.

Amino Acid Sequence↗

Gene regulation technologies for gene and cell therapy.

Gene therapy stands at the forefront of medical innovation, offering unique potential to treat the underlying causes of genetic disorders and broadly enable regenerative medicine. However, unregulated production of therapeutic genes can lead to decreased clinical utility due to various complications. Thus, many technologies for controlled gene expression are under development, including regulated transgenes, modulation of endogenous genes to leverage native biological regulation, mapping and repurposing of transcriptional regulatory networks, and engineered systems that dynamically react to cell state changes. Transformative therapies enabled by advances in tissue-specific promoters, inducible systems, and targeted delivery have already entered clinical testing and demonstrated significantly improved specificity and efficacy. This review highlights next-generation technologies under development to expand the reach of gene therapies by enabling precise modulation of gene expression. These technologies, including epigenome editing, antisense oligonucleotides, RNA editing, transcription factor-mediated reprogramming, and synthetic genetic circuits, have the potential to provide powerful control over cellular functions. Despite these remarkable achievements, challenges remain in optimizing delivery, minimizing off-target effects, and addressing regulatory hurdles. However, the ongoing integration of biological insights with engineering innovations promises to expand the potential for gene therapy, offering hope for treating not only rare genetic disorders but also complex multifactorial diseases.

Humans↗

Easy first steps and their implication to the use of a mouse-based and a script-based strategy.

The present study evaluated the convention to design training environments by giving access to easy strategies first and progressing to more difficult and efficient strategies thereafter. An experiment was conducted focusing on training in a simplified editing task. This task could be performed with an easy (mouse-based) strategy as well as with a more efficient (script-based) strategy. Two learning environments were compared, based on the order of the introduction of the following 2 strategies to participants: an easy-first program and a difficult-first program. The results highlight 2 interesting patterns. First, initial training in an easy strategy impaired the acquisition of a more efficient strategy. Second, learning the easy strategy first reduced between-subjects variability. It helped poor performers but resulted in a lower proportion of high-level performers.

Choice Behavior↗

Recognition of shapes by editing their shock graphs.

This paper presents a novel framework for the recognition of objects based on their silhouettes. The main idea is to measure the distance between two shapes as the minimum extent of deformation necessary for one shape to match the other. Since the space of deformations is very high-dimensional, three steps are taken to make the search practical: 1) define an equivalence class for shapes based on shock-graph topology, 2) define an equivalence class for deformation paths based on shock-graph transitions, and 3) avoid complexity-increasing deformation paths by moving toward shock-graph degeneracy. Despite these steps, which tremendously reduce the search requirement, there still remain numerous deformation paths to consider. To that end, we employ an edit-distance algorithm for shock graphs that finds the optimal deformation path in polynomial time. The proposed approach gives intuitive correspondences for a variety of shapes and is robust in the presence of a wide range of visual transformations. The recognition rates on two distinct databases of 99 and 216 shapes each indicate highly successful within category matches (100 percent in top three matches), which render the framework potentially usable in a range of shape-based recognition applications.

Algorithms↗

Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study.

BACKGROUND: Few longitudinal studies of dementia in Parkinson disease (PD) have been reported, and the proportion of patients with PD who eventually develop dementia is unknown. OBJECTIVE: To examine the 8-year prevalence, characteristics, and risk factors of dementia in patients with PD. METHODS: Patients were recruited from an epidemiological study of PD in the county of Rogaland, Norway, using explicit criteria for PD. Subjects with cognitive impairment at disease onset were excluded. A semistructured caregiver-based interview, cognitive rating scales, and neuropsychological tests were used to diagnose dementia according to criteria from the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition at baseline and 4 and 8 years later. A population-based sample of 3295 subjects in the municipality of Odense, Denmark, was used as a comparison group and examined at baseline and after 2 and 5 years. RESULTS: We included 224 patients with PD (116 women). At baseline, 51 patients (26%) had dementia. Fifty-five patients died, and 10 refused follow-up without their dementia status known. Forty-three and 28 new cases of dementia were identified at the 4- and 8-year evaluations, respectively. The 4-year prevalence of dementia in PD was nearly 3 times higher than in the non-PD group. The 8-year prevalence in PD was 78.2% (95% confidence interval [CI], 71.1-84.0). Risk factors for dementia were hallucinations before baseline (odds ratio [OR] = 3.1; 95% CI, 1.6-6.2) and akinetic-dominant or mixed tremor/akinetic PD (OR = 3.3; 95% CI, 1.2-8.5). CONCLUSIONS: More than three quarters of this representative PD cohort developed dementia during the 8-year study period. Early hallucinations and akinetic-dominant PD were associated with an increased risk of dementia.

Aged↗