Stem cell populations in meristematic tissues at distinct locations in the plant body provide the potency of continuous plant growth. Primary meristems, at the apices of the plant body, contribute ...mainly to the elongation of the main plant axes, whereas secondary meristems in lateral positions are responsible for the thickening of these axes. The stem cells of the vascular cambium-a secondary lateral meristem-produce the secondary phloem (bast) and secondary xylem (wood). The sites of primary and secondary growth are spatially separated, and mobile signals are expected to coordinate growth rates between apical and lateral stem cell populations. Although the underlying mechanisms have not yet been uncovered, it seems likely that hormones, peptides, and mechanical cues orchestrate primary and secondary growth. In this review, we highlight the current knowledge and recent discoveries of how cambial stem cell activity is regulated, with a focus on mobile signals and the response of cambial activity to environmental and stress factors.
Summary Background Unexplained differences between classes of antihypertensive drugs in their effectiveness in preventing stroke might be due to class effects on intraindividual variability in blood ...pressure. We did a systematic review to assess any such effects in randomised controlled trials. Methods Baseline and follow-up data for mean (SD) of systolic blood pressure (SBP) were extracted from trial reports. Effect of treatment on interindividual variance (SD2 ) in blood pressure (a surrogate for within-individual variability), expressed as the ratio of the variances (VR), was related to effects on clinical outcomes. Pooled estimates were derived by use of random-effects meta-analysis. Findings Mean (SD) SBP at follow-up was reported in 389 (28%) of 1372 eligible trials. There was substantial heterogeneity between trials in VR (p<1×10−40 ), 68% of which was attributable to allocated drug class. Compared with other drugs, interindividual variation in SBP was reduced by calcium-channel blockers (VR 0·81, 95% CI 0·76–0·86, p<0·0001) and non-loop diuretic drugs (0·87, 0·79–0·96, p=0·007), and increased by angiotensin-converting enzyme (ACE) inhibitors (1·08, 1·02–1·15, p=0·008), angiotensin-receptor blockers (1·16, 1·07–1·25, p=0·0002), and β blockers (1·17, 1·07–1·28, p=0·0007). Compared with placebo only, interindividual variation in SBP was reduced the most by calcium-channel blockers (0·76, 0·67–0·85, p<0·0001). Effects were consistent in parallel group and crossover design trials, and in analyses of dose-response. Across all trials, effects of treatment on VR of SBP ( r2 =0·372, p=0·0006) and on mean SBP ( r2 =0·328, p=0·0015) accounted for effects on stroke risk (eg, odds ratio 0·79, 0·71–0·87, p<0·0001, for VR≤0·80), and both remained significant in a combined model. Interpretation Drug-class effects on interindividual variation in blood pressure can account for differences in effects of antihypertensive drugs on risk of stroke independently of effects on mean SBP. Funding None.
Intravenous thrombolytics and endovascular thrombectomy for ischemic stroke have evolved in parallel. However, the best approach to combine these reperfusion therapies in patients eligible for both ...strategies remains uncertain. Initial randomized trials of endovascular thrombectomy included administration of intravenous thrombolytics to all eligible patients. However, whether that is of net benefit has been questioned and parallels drawn with treatment of ST-segment-elevation myocardial infarction, where intravenous thrombolytics are only given if first medical contact to percutaneous intervention is expected to be >90 minutes. Six randomized trials of a direct thrombectomy approach versus intravenous thrombolytics followed by endovascular thrombectomy have now reported their results. With exception of a minority of patients in one trial, the trials all used alteplase rather than potentially more effective tenecteplase. This review examines the current state of evidence and implications for clinical practice. Importantly, these trials only apply to patients who present to a hospital with immediate access to endovascular thrombectomy and are not relevant to patients who receive thrombolytic and are then transferred to an endovascular-capable hospital. Although 2 of the 6 randomized trials met their prespecified noninferiority margin, these margins were large compared with the absolute benefit of alteplase. Overall, functional outcome was similar, with slight trends favoring bridging thrombolytics and a significant increase in final reperfusion. Symptomatic hemorrhage was increased by ≈1.8% in the bridging group but death was nonsignificantly lower. The workflow in direct thrombectomy trials involved delaying thrombolytic administration until eligibility for thrombectomy and the trials was established and randomization completed. This reduced the time available for thrombolytics to occur prethrombectomy compared with standard practice. We conclude that, pending individual-patient data meta-analyses, intravenous thrombolytics retain an important role alongside endovascular thrombectomy. Further efforts to accelerate and enhance reperfusion with thrombolytics and perform individual patient-level pooled subgroup analyses are warranted.
Since 2015, a series of endovascular trials transformed the management of patients with large vessel occlusion stroke. Most thrombectomy trials used restrictive eligibility criteria to optimize the ...chances of showing that thrombectomy could work. The problem arises when generalizing trial results into evidence-based recommendations. Many organizations, oblivious of this problem, translated verbatim restrictive trial eligibility criteria into authoritative guidelines, which limit the use of thrombectomy to highly selected patients. The clinical problem becomes as follows: what to do for all other stroke patients equally in need of care? The cycle of restrictive trial eligibility criteria, corresponding restrictive guidelines, observational studies of unvalidated practices showing other patients benefit, a new trial is needed, has been repeated often. Thrombectomy trials ought to have included all patients that could potentially benefit. If the signal that was looked for by restricting eligibility is at risk of being lost in the noise generated by the heterogeneity of patients, D. Sackett proposed a solution: to use the same criteria, not to select some patients and exclude others but to prespecify the subgroup of patients most likely to benefit. In this commentary, we propose a tiered approach, where the boundaries of treatment beneficiaries can be more rigorously tested and confirmed. Identification of these patients before the development of guidelines, which would have otherwise neglected these individuals, may open innumerable treatment opportunities to those who will instead be denied of them.
Endovascular treatment is a highly effective therapy for acute ischemic stroke due to large vessel occlusion and has recently revolutionized stroke care. Oftentimes, ischemic core extent on baseline ...imaging is used to determine endovascular treatment-eligibility. There are, however, 3 fundamental issues with the core conceptFirst, computed tomography and magnetic resonance imaging, which are mostly used in the acute stroke setting, are not able to precisely determine whether and to what extent brain tissue is infarcted (core) or still viable, due to variability in tissue vulnerability, the phenomenon of selective neuronal loss and lack of a reliable gold standard. Second, treatment decision-making in acute stroke is multifactorial, and as such, the relative importance of single variables, including imaging factors, is reduced. Third, there are often discrepancies between core volume and clinical outcome. This review will address the uncertainty in terminology and proposes a direction towards more clarity. This theoretical exercise needs empirical data that clarify the definitions further and prove its value.
Trees represent the largest terrestrial carbon sink and a renewable source of ligno-cellulose. There is significant scope for yield and quality improvement in these largely undomesticated species, ...and efforts to engineer elite varieties will benefit from improved understanding of the transcriptional network underlying cambial growth and wood formation. We generated highspatial- resolution RNA sequencing data spanning the secondary phloem, vascular cambium, and wood-forming tissues of Populus tremula. The transcriptome comprised 28,294 expressed, annotated genes, 78 novel protein-coding genes, and 567 putative long intergenic noncoding RNAs. Most paralogs originating from the Salicaceae whole-genome duplication had diverged expression, with the exception of those highly expressed during secondary cell wall deposition. Coexpression network analyses revealed that regulation of the transcriptome underlying cambial growth and wood formation comprises numerous modules forming a continuum of active processes across the tissues. A comparative analysis revealed that a majority of these modules are conserved in Picea abies. The high spatial resolution of our data enabled identification of novel roles for characterized genes involved in xylan and cellulose biosynthesis, regulators of xylem vessel and fiber differentiation and lignification. An associated web resource (AspWood, http://aspwood.popgenie.org) provides interactive tools for exploring the expression profiles and coexpression network.
Organ size homeostasis, compensatory growth to replace lost tissue, requires constant measurement of size and adjustment of growth rates. Morphogen gradients control organ and tissue sizes by ...regulating stem cell activity, cell differentiation, and removal in animals 1–3. In plants, control of tissue size is of specific importance in root caps to protect the growing root tip from mechanical damage 4. New root cap tissue is formed by the columella and lateral root-cap-epidermal stem cells, whose activity is regulated through non-dividing niche-like cells, the quiescent center (QC) 4, 5. Columella daughter cells in contact with the QC retain the potency to divide, while derivatives oriented toward the mature cap undergo differentiation. The outermost columella layers are sequentially separated from the root body, involving remodeling of cell walls 6. Factors regulating the balance between cell division, elongation, and separation to keep root cap size constant are currently unknown 4. Here, we report that stem cell proliferation induced cell separation at the periphery of the root cap, resulting in tissue size homeostasis. An auxin response gradient with a maximum in the QC and a minimum in the detaching layer was established prior to the onset of cell separation. In agreement with a mathematical model, tissue size was positively regulated by the amount of auxin released from the source. Auxin transporters localized non-polarly to plasma membranes of the inner cap, partly isolating separating layers from the auxin source. Together, these results are in support of an auxin gradient measuring and regulating tissue size.
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•Root cap size is kept constant through repetitive cell division-separation cycles•A local auxin gradient orchestrates cell division and separation•Cell division occurs at an auxin maximum—separation at a minimum•The gradient is independent of active directional auxin transport
Dubreuil et al. investigated the regulation of tissue size homeostasis of the apical root cap in Arabidopsis. They show that the root cap size is kept constant by successive cycles of cell division and separation. Tissue size homeostasis is coordinated by an auxin gradient with a maximum in the stem cells and a minimum in the separating cells.
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