Amino acids biosynthesis in root hair development: a mini-review.

Metabolic factors are essential for developmental biology of an organism. In plants, roots fulfill important functions, in part due to the development of specific epidermal cells, called hair cells that form root hairs (RHs) responsible for water and mineral uptake. RH development consists in (a) patterning processes involved in formation of hair and non-hair cells developed from trichoblasts and atrichoblasts; (b) RH initiation; and (c) apical (tip) growth of the RH. Here we review how these processes depend on pools of different amino acids and what is known about RH phenotypes of mutants disrupted in amino acid biosynthesis. This analysis shows that some amino acids, particularly aromatic ones, are required for RH apical (tip) growth, and that not much is known about the role of amino acids at earlier stages of RH formation. We also address the role of amino acids in rhizosphere, inhibitory and stimulating effects of amino acids on RH growth, amino acids as N source in plant nutrition, and amino acid transporters and their expression in the RHs. Amino acids form conjugates with auxin, a hormone essential for RH growth, and respective genes are overviewed. Finally, we outline missing links and envision some perspectives in the field.

Reproducibility of arterial spin labeling cerebral blood flow image processing: A report of the ISMRM open science initiative for perfusion imaging (OSIPI) and the ASL MRI challenge.

PURPOSE: Arterial spin labeling (ASL) is a widely used contrast-free MRI method for assessing cerebral blood flow (CBF). Despite the generally adopted ASL acquisition guidelines, there is still wide variability in ASL analysis. We explored this variability through the ISMRM-OSIPI ASL-MRI Challenge, aiming to establish best practices for more reproducible ASL analysis. METHODS: Eight teams analyzed the challenge data, which included a high-resolution T1-weighted anatomical image and 10 pseudo-continuous ASL datasets simulated using a digital reference object to generate ground-truth CBF values in normal and pathological states. We compared the accuracy of CBF quantification from each team's analysis to the ground truth across all voxels and within predefined brain regions. Reproducibility of CBF across analysis pipelines was assessed using the intra-class correlation coefficient (ICC), limits of agreement (LOA), and replicability of generating similar CBF estimates from different processing approaches. RESULTS: Absolute errors in CBF estimates compared to ground-truth synthetic data ranged from 18.36 to 48.12 mL/100 g/min. Realistic motion incorporated into three datasets produced the largest absolute error and variability between teams, with the least agreement (ICC and LOA) with ground-truth results. Fifty percent of the submissions were replicated, and one produced three times larger CBF errors (46.59 mL/100 g/min) compared to submitted results. CONCLUSIONS: Variability in CBF measurements, influenced by differences in image processing, especially to compensate for motion, highlights the significance of standardizing ASL analysis workflows. We provide a recommendation for ASL processing based on top-performing approaches as a step toward ASL standardization.

A biostimulant yeast, Hanseniaspora opuntiae, modifies Arabidopsis thaliana root architecture and improves the plant defense response against Botrytis cinerea.

MAIN CONCLUSION: The biostimulant Hanseniaspora opuntiae regulates Arabidopsis thaliana root development and resistance to Botrytis cinerea. Beneficial microbes can increase plant nutrient accessibility and uptake, promote abiotic stress tolerance, and enhance disease resistance, while pathogenic microorganisms cause plant disease, affecting cellular homeostasis and leading to cell death in the most critical cases. Commonly, plants use specialized pattern recognition receptors to perceive beneficial or pathogen microorganisms. Although bacteria have been the most studied plant-associated beneficial microbes, the analysis of yeasts is receiving less attention. This study assessed the role of Hanseniaspora opuntiae, a fermentative yeast isolated from cacao musts, during Arabidopsis thaliana growth, development, and defense response to fungal pathogens. We evaluated the A. thaliana-H. opuntiae interaction using direct and indirect in vitro systems. Arabidopsis growth was significantly increased seven days post-inoculation with H. opuntiae during indirect interaction. Moreover, we observed that H. opuntiae cells had a strong auxin-like effect in A. thaliana root development during in vitro interaction. We show that 3-methyl-1-butanol and ethanol are the main volatile compounds produced by H. opuntiae. Subsequently, it was determined that A. thaliana plants inoculated with H. opuntiae have a long-lasting and systemic effect against Botrytis cinerea infection, but independently of auxin, ethylene, salicylic acid, or jasmonic acid pathways. Our results demonstrate that H. opuntiae is an important biostimulant that acts by regulating plant development and pathogen resistance through different hormone-related responses.

Aromatic amino acid biosynthesis impacts root hair development and symbiotic associations in Lotus japonicus.

Legume roots can be symbiotically colonized by arbuscular mycorrhizal (AM) fungi and nitrogen-fixing bacteria. In Lotus japonicus, the latter occurs intracellularly by the cognate rhizobial partner Mesorhizobium loti or intercellularly with the Agrobacterium pusense strain IRBG74. Although these symbiotic programs show distinctive cellular and transcriptome signatures, some molecular components are shared. In this study, we demonstrate that 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase 1 (DAHPS1), the first enzyme in the biosynthetic pathway of aromatic amino acids (AAAs), plays a critical role in root hair development and for AM and rhizobial symbioses in Lotus. Two homozygous DAHPS1 mutants (dahps1-1 and dahps1-2) showed drastic alterations in root hair morphology, associated with alterations in cell wall dynamics and a progressive disruption of the actin cytoskeleton. The altered root hair structure was prevented by pharmacological and genetic complementation. dahps1-1 and dahps1-2 showed significant reductions in rhizobial infection (intracellular and intercellular) and nodule organogenesis and a delay in AM colonization. RNAseq analysis of dahps1-2 roots suggested that these phenotypes are associated with downregulation of several cell wall-related genes, and with an attenuated signaling response. Interestingly, the dahps1 mutants showed no detectable pleiotropic effects, suggesting a more selective recruitment of this gene in certain biological processes. This work provides robust evidence linking AAA metabolism to root hair development and successful symbiotic associations.

Gilteritinib in Combination With Induction and Consolidation Chemotherapy and as Maintenance Therapy: A Phase IB Study in Patients With Newly Diagnosed AML.

PURPOSE: Gilteritinib is a type 1 FLT3 inhibitor active as monotherapy for relapsed or refractory FLT3-mutated AML. We investigated the safety, tolerability, and efficacy of gilteritinib incorporated into intensive induction and consolidation chemotherapy, and as maintenance therapy for adult patients with newly diagnosed, non-favorable-risk AML. METHODS: In this phase IB study (2215-CL-0103; ClinicalTrials.gov identifier: NCT02236013), 103 participants were screened and 80 were allocated to treatment. The study was divided into four parts: dose escalation, dose expansion, investigation of alternate anthracycline and gilteritinib schedule, and continuous gilteritinib during consolidation. RESULTS: After dose escalation, 120 mg gilteritinib once daily was chosen for further study. There were 58 participants evaluable for response at this dose, 36 of whom harbored FLT3 mutations. For participants with FLT3-mutated AML, the composite complete response (CRc) rate was 89% (83% were conventional complete responses), all achieved after a single induction cycle. The median overall survival time was 46.1 months. Gilteritinib was well-tolerated in this context although the median time to count recovery during induction was approximately 40 days. Longer time-to-count recovery was associated with higher trough levels of gilteritinib, which, in turn, were associated with azole use. The recommended regimen is gilteritinib at a dose of 120 mg once daily from days 4 to 17 or 8 to 21 of a 7 + 3 induction with either idarubicin or daunorubicin and from day 1 continuously with high-dose cytarabine consolidation. Maintenance therapy with gilteritinib was well-tolerated. CONCLUSION: These results demonstrated the safety and tolerability of gilteritinib incorporated into an induction and consolidation chemotherapy regimen, and as single-agent maintenance therapy for patients with newly diagnosed FLT3-mutant AML. The data herein provide an important framework for the design of randomized trials comparing gilteritinib with other FLT3 inhibitors.

Extending resolution within a single imaging frame.

The resolution of fluorescence microscopy images is limited by the physical properties of light. In the last decade, numerous super-resolution microscopy (SRM) approaches have been proposed to deal with such hindrance. Here we present Mean-Shift Super Resolution (MSSR), a new SRM algorithm based on the Mean Shift theory, which extends spatial resolution of single fluorescence images beyond the diffraction limit of light. MSSR works on low and high fluorophore densities, is not limited by the architecture of the optical setup and is applicable to single images as well as temporal series. The theoretical limit of spatial resolution, based on optimized real-world imaging conditions and analysis of temporal image stacks, has been measured to be 40 nm. Furthermore, MSSR has denoising capabilities that outperform other SRM approaches. Along with its wide accessibility, MSSR is a powerful, flexible, and generic tool for multidimensional and live cell imaging applications.

Changing the name of diabetes insipidus: a position statement of the working group to consider renaming diabetes insipidus

"What's in a name? That which we call a rose / By any other name would smell as sweet" (Juliet, from Romeo and Juliet by William Shakespeare). Shakespeare's implication is that a name is nothing but a word and it therefore represents a convention with no intrinsic meaning. Whilst this may be relevant to romantic literature, disease names do have real meanings, and consequences, in medicine. Hence, there must be a very good rational for changing the name of a disease that has a centuries-old historical context. A working group of representatives from national and international endocrinology and endocrine pediatric societies now proposes changing the name of "diabetes insipidus" to "Arginine Vasopressin Deficiency (AVP-D)" for central etiologies, and "Arginine Vasopressin Resistance (AVP-R)" for nephrogenic etiologies This editorial provides both the historical context and the rational for this proposed name change.

Changing the name of diabetes insipidus: a position statement of the working group to consider renaming diabetes insipidus.

"What's in a name? That which we call a rose / By any other name would smell as sweet" (Juliet, from Romeo and Juliet by William Shakespeare). Shakespeare's implication is that a name is nothing but a word and it therefore represents a convention with no intrinsic meaning. Whilst this may be relevant to romantic literature, disease names do have real meanings, and consequences, in medicine. Hence, there must be a very good rational for changing the name of a disease that has a centuries-old historical context. A working group of representatives from national and international endocrinology and endocrine pediatric societies now proposes changing the name of "diabetes insipidus" to "Arginine Vasopressin Deficiency (AVP-D)" for central etiologies, and "Arginine Vasopressin Resistance (AVP-R)" for nephrogenic etiologies This editorial provides both the historical context and the rational for this proposed name change.

A mutation in THREONINE SYNTHASE 1 uncouples proliferation and transition domains of the root apical meristem: experimental evidence and in silico proposed mechanism.

A continuum from stem to transit-amplifying to a differentiated cell state is a common theme in multicellular organisms. In the plant root apical meristem (RAM), transit-amplifying cells are organized into two domains: cells from the proliferation domain (PD) are displaced to the transition domain (TD), suggesting that both domains are necessarily coupled. Here, we show that in the Arabidopsis thaliana mto2-2 mutant, in which threonine (Thr) synthesis is affected, the RAM lacks the PD. Through a combination of cell length profile analysis, mathematical modeling and molecular markers, we establish that the PD and TD can be uncoupled. Remarkably, although the RAM of mto2-2 is represented solely by the TD, the known factors of RAM maintenance and auxin signaling are expressed in the mutant. Mathematical modeling predicts that the stem cell niche depends on Thr metabolism and that, when disturbed, the normal continuum of cell states becomes aborted.

Use of Needle Localization in the Surgical Management of Non-seroma, Mass-forming BIA-ALCL.

Outcomes related to the treatment of breast implant-associated anaplastic large cell lymphoma, a rare extranodal T-cell lymphoma associated with textured breast implants, are largely dependent on the successful resection to negative margins via en bloc capsulectomy and resection of any associated masses. To date, the use of needle localization, a common technique used in breast surgery, to assist in the complete removal of breast implant-associated anaplastic large cell lymphoma has not been described. We present the case report of a 66-year-old woman, with a previous medical history of left-sided invasive ductal carcinoma, who presented 7 years after textured breast implant placement with a left-sided mass without peri-implant seroma. Biopsy demonstrated breast implant-associated anaplastic large cell lymphoma and the associated breast mass extended beyond the capsule borders. The present report describes the novel use of needle localization in this patient to facilitate the complete removal of the malignancy-associated mass with maximal preservation of the overlying soft tissue envelope.

Acupuncture and Global Health: Providing Medical Acupuncture Education and Service in Georgetown, Guyana.

Objective: Guyana is located on the north coast of the South American continent and is a middle-income developing country in the Caribbean. There is little educational opportunity for individuals interested in medical acupuncture. The aim of this project was to develop an introductory medical acupuncture curriculum for perioperative use. Materials and Methods: Through a carefully coordinated teaching-and-care plan, with support from physicians and various medical organizations, an educational opportunity in medical acupuncture was established at the Georgetown Public Hospital Corporation, a medical university teaching hospital in Georgetown, Guyana. The project involved development of a medical acupuncture curriculum, as well as teaching and patient care. Anesthesia staff members, resident trainees, and perioperative and pain-clinic patients participated. Results: Medical acupuncture-trained physicians were able to provide medical acupuncture education and services in a third-world country because of this project. Conclusion: This project is an ideal example of utilizing medical acupuncture for promoting global heath.

Image-Free Robotic-Assisted Total Knee Arthroplasty Improves Implant Alignment Accuracy: A Cadaveric Study.

BACKGROUND: Improving resection accuracy and eliminating outliers in total knee arthroplasty (TKA) is important to improving patient outcomes regardless of alignment philosophy. Robotic-assisted surgical systems improve resection accuracy and reproducibility compared to conventional instrumentation. Some systems require preoperative imaging while others rely on intraoperative anatomic landmarks. We hypothesized that the alignment accuracy of a novel image-free robotic-assisted surgical system would be equivalent or better than conventional instrumentation with fewer outliers. METHODS: Forty cadaveric specimens were used in this study. Five orthopedic surgeons performed 8 bilateral TKAs each, using the VELYS Robotic-Assisted System (DePuy Synthes) and conventional instrumentation on contralateral knees. Pre-resection and postresection computed tomography scans, along with optical scans of the implant positions were performed to quantify resection accuracies relative to the alignment targets recorded intraoperatively. RESULTS: The robotic-assisted cohort demonstrated smaller resection errors compared to conventional instrumentation in femoral coronal alignment (0.63° ± 0.50° vs 1.39° ± 0.95°, P < .001), femoral sagittal alignment (1.21° ± 0.90° vs 3.27° ± 2.51°, P < .001), and tibial coronal alignment (0.93° ± 0.72° vs 1.65° ± 1.29°, P = .001). All other resection angle accuracies were equivalent. Similar improvements were found in the femoral implant coronal alignment (0.89° ± 0.82° vs 1.42° ± 1.15°, P = .011), femoral implant sagittal alignment (1.51° ± 1.08° vs 2.49° ± 2.10°, P = .006), and tibial implant coronal alignment (1.31° ± 0.84° vs 2.03° ± 1.44°, P = .004). The robotic-assisted cohort had fewer outliers (errors >3°) for all angular resection alignments. CONCLUSION: This in vitro study demonstrated that image-free robotic-assisted TKA can improve alignment accuracy compared to conventional instrumentation and reduce the incidence of outliers.

Cellular and molecular bases of lateral root initiation and morphogenesis.

Lateral root development is essential for the establishment of the plant root system. Lateral root initiation is a multistep process that impacts early primordium morphogenesis and is linked to the formation of a morphogenetic field of pericycle founder cells. Gradual recruitment of founder cells builds this morphogenetic field in an auxin-dependent manner. The complex process of lateral root primordium morphogenesis includes several subprocesses, which are presented in this review. The underlying cellular and molecular mechanisms of these subprocesses are examined.

Alzheimer's Dementia After Exposure to Anesthesia and Surgery in the Elderly: A Matched Natural Experiment Using Appendicitis.

OBJECTIVE: The aim of this study was to determine whether surgery and anesthesia in the elderly may promote Alzheimer disease and related dementias (ADRD). BACKGROUND: There is a substantial conflicting literature concerning the hypothesis that surgery and anesthesia promotes ADRD. Much of the literature is confounded by indications for surgery or has small sample size. This study examines elderly patients with appendicitis, a common condition that strikes mostly at random after controlling for some known associations. METHODS: A matched natural experiment of patients undergoing appendectomy for appendicitis versus control patients without appendicitis using Medicare data from 2002 to 2017, examining 54,996 patients without previous diagnoses of ADRD, cognitive impairment, or neurological degeneration, who developed appendicitis between ages 68 through 77 years and underwent an appendectomy (the ''Appendectomy'' treated group), matching them 5:1 to 274,980 controls, examining the subsequent hazard for developing ADRD. RESULTS: The hazard ratio (HR) for developing ADRD or death was lower in the Appendectomy group than controls: HR = 0.96 [95% confidence interval (CI) 0.94-0.98], P < 0.0001, (28.2% in Appendectomy vs 29.1% in controls, at 7.5 years). The HR for death was 0.97 (95% CI 0.95-0.99), P = 0.002, (22.7% vs 23.1% at 7.5 years). The HR for developing ADRD alone was 0.89 (95% CI 0.86-0.92), P < 0.0001, (7.6% in Appendectomy vs 8.6% in controls, at 7.5 years). No subgroup analyses found significantly elevated rates of ADRD in the Appendectomy group. CONCLUSION: In this natural experiment involving 329,976 elderly patients, exposure to appendectomy surgery and anesthesia did not increase the subsequent rate of ADRD.

Live Plant Cell Tracking: Fiji plugin to analyze cell proliferation dynamics and understand morphogenesis.

Arabidopsis (Arabidopsis thaliana) primary and lateral roots (LRs) are well suited for 3D and 4D microscopy, and their development provides an ideal system for studying morphogenesis and cell proliferation dynamics. With fast-advancing microscopy techniques used for live-imaging, whole tissue data are increasingly available, yet present the great challenge of analyzing complex interactions within cell populations. We developed a plugin "Live Plant Cell Tracking" (LiPlaCeT) coupled to the publicly available ImageJ image analysis program and generated a pipeline that allows, with the aid of LiPlaCeT, 4D cell tracking and lineage analysis of populations of dividing and growing cells. The LiPlaCeT plugin contains ad hoc ergonomic curating tools, making it very simple to use for manual cell tracking, especially when the signal-to-noise ratio of images is low or variable in time or 3D space and when automated methods may fail. Performing time-lapse experiments and using cell-tracking data extracted with the assistance of LiPlaCeT, we accomplished deep analyses of cell proliferation and clonal relations in the whole developing LR primordia and constructed genealogical trees. We also used cell-tracking data for endodermis cells of the root apical meristem (RAM) and performed automated analyses of cell population dynamics using ParaView software (also publicly available). Using the RAM as an example, we also showed how LiPlaCeT can be used to generate information at the whole-tissue level regarding cell length, cell position, cell growth rate, cell displacement rate, and proliferation activity. The pipeline will be useful in live-imaging studies of roots and other plant organs to understand complex interactions within proliferating and growing cell populations. The plugin includes a step-by-step user manual and a dataset example that are available at https://www.ibt.unam.mx/documentos/diversos/LiPlaCeT.zip.

On the normalized power prior.

The power prior is a popular tool for constructing informative prior distributions based on historical data. The method consists of raising the likelihood to a discounting factor in order to control the amount of information borrowed from the historical data. However, one often wishes to assign this discounting factor a prior distribution and estimate it jointly with the parameters, which in turn necessitates the computation of a normalizing constant. In this article, we are concerned with how to approximately sample from joint posterior of the parameters and the discounting factor. We first show a few important properties of the normalizing constant and then use these results to motivate a bisection-type algorithm for computing it on a fixed budget of evaluations. We give a large array of illustrations and discuss cases where the normalizing constant is known in closed-form and where it is not. We show that the proposed method produces approximate posteriors that are very close to the exact distributions and also produces posteriors that cover the data-generating parameters with higher probability in the intractable case. Our results suggest that the proposed method is an accurate and easy to implement technique to include this normalization, being applicable to a large class of models. They also reinforce the notion that proper inclusion of the normalizing constant is crucial to the drawing of correct inferences and appropriate quantification of uncertainty.

The quiescent centre and root apical meristem: organization and function.

This special issue is dedicated to the 100th anniversary of the birth of Frederick Albert Lionel Clowes, who discovered the quiescent centre (QC) of the root apical meristem (RAM). His discovery was a foundation for contemporary studies of the QC and RAM function, maintenance, and organization. RAM function is fundamental for cell production and root growth. This special issue bundles reviews on the main tendencies, hypotheses, and future directions, and identifies unknowns in the field.

Interkingdom Comparison of Threonine Metabolism for Stem Cell Maintenance in Plants and Animals.

In multicellular organisms, tissue generation, maintenance, and homeostasis depend on stem cells. Cellular metabolic status is an essential component of different differentiated states, from stem to fully differentiated cells. Threonine (Thr) metabolism has emerged as a critical factor required to maintain pluripotent/multipotent stem cells in both plants and animals. Thus, both kingdoms conserved or converged upon this fundamental feature of stem cell function. Here, we examine similarities and differences in Thr metabolism-dependent mechanisms supporting stem cell maintenance in these two kingdoms. We then consider common features of Thr metabolism in stem cell maintenance and predict and speculate that some knowledge about Thr metabolism and its role in stem cell function in one kingdom may apply to the other. Finally, we outline future research directions to explore these hypotheses.

The quiescent centre of the root apical meristem: conceptual developments from Clowes to modern times.

In this review we discuss the concepts of the quiescent centre (QC) of the root apical meristem (RAM) and their change over time, from their formulation by F.A.L. Clowes to the present. This review is dedicated to the 100th anniversary of the birth of Clowes, and we present his short biography and a full bibliography of Clowes' work. Over time, the concept of the QC proved to be useful for the understanding of RAM organization and behaviour. We focus specifically on conceptual developments, from the organization of the QC to understanding its functions in RAM maintenance and activity, ranging from a model species, Arabidopsis thaliana, to crops. Concepts of initial cells, stem cells, and heterogeneity of the QC cells in the context of functional and structural stem cells are considered. We review the role of the QC in the context of cell flux in the RAM and the nature of quiescence of the QC cells. We discuss the origin of the QC and fluctuation of its size in ontogenesis and why the QC cells are more resistant to stress. Contemporary concepts of the organizer and stem cell niche are also considered. We also propose how the stem cell niche in the RAM can be defined in roots of a non-model species.

Work, Stressors, and Psychosocial Adjustment of Undocumented Guatemalan Adolescents in United States Agriculture: A Mixed-Methods Approach.

This research focused on undocumented male Guatemalan migrant adolescents' experiences and stressors in United States agriculture. Study 1 applied a phenomenological method to explore work-life experiences of Guatemalan minors (n = 10) aged 15-17 (Mage = 16.4). Findings highlighted three themes (1) "Just keep pushing forward," (2) "It feels ugly but that's life," and (3) "I have to do everything on my own." Using a separate sample, Study 2 examined the association between stressors and depressive symptoms among Guatemalan migrant adolescents (n = 28), aged 15-20 (Mage = 17.71). Results showed loneliness, social isolation, and work conditions as correlates for depressive symptoms. Findings highlighted a distinct developmental path among migrant farmworker adolescents and offered insight into their resilience and developmental threats.