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Organ formation in animals and plants relies on precise control of cell state transitions to turn stem cell daughters into fully differentiated cells. In plants, cells cannot rearrange due to shared cell walls. Thus, differentiation progression and the accompanying cell expansion must be tightly coordinated across tissues. PLETHORA (PLT) transcription factor gradients are unique in their ability to guide the progression of cell differentiation at different positions in the growing Arabidopsis thaliana root, which contrasts with well-described transcription factor gradients in animals specifying distinct cell fates within an essentially static context. To understand the output of the PLT gradient, we studied the gene set transcriptionally controlled by PLTs. Our work reveals how the PLT gradient can regulate cell state by region-specific induction of cell proliferation genes and repression of differentiation. Moreover, PLT targets include major patterning genes and autoregulatory feedback components, enforcing their role as master regulators of organ development., (© 2016 American Society of Plant Biologists. All rights reserved.)

Directional transport of auxin is essential for plant development, with PIN auxin transport proteins representing an integral part of the machinery that controls hormone distribution. However, unlike the rapidly emerging framework of molecular determinants regulating PIN protein abundance and subcellular localization, insights into mechanisms controlling PIN transcription are still limited. Here we describe PIN2 PROMOTER BINDING PROTEIN 1 (PPP1), an evolutionary conserved plant-specific DNA binding protein that acts on transcription of PIN genes. Consistent with PPP1 DNA-binding activity, PPP1 reporter proteins are nuclear localized and analysis of PPP1 null alleles and knockdown lines indicated a function as a positive regulator of PIN expression. Furthermore, we show that ppp1 pleiotropic mutant phenotypes are partially reverted by PIN overexpression, and results are presented that underline a role of PPP1-PIN promoter interaction in PIN expression control. Collectively, our findings identify an elementary, thus far unknown, plant-specific DNA-binding protein required for post-embryonic plant development, in general, and correct expression of PIN genes, in particular.

Main Conclusion: SCARECROW controls Arabidopsis root meristem size from the root endodermis tissue by regulating the DELLA protein RGA that in turn mediates the regulation of ARR1 levels at the transition zone. Coherent organ growth requires a fine balance between cell division and cell differentiation. Intriguingly, plants continuously develop organs post-embryonically thanks to the activity of meristems that allow growth and environmental plasticity. In Arabidopsis thaliana, continued root growth is assured when division of the distal stem cell and their daughters is balanced with cell differentiation at the meristematic transition zone (TZ). We have previously shown that at the TZ, the cytokinin-dependent transcription factor ARR1 controls the rate of differentiation commitment of meristematic cells and that its activities are coordinated with those of the distal stem cells by the gene SCARECROW (SCR). In the stem cell organizer (the quiescent center, QC), SCR directly suppresses ARR1 both sustaining stem cell activities and titrating non-autonomously the ARR1 transcript levels at the TZ via auxin. Here, we show that SCR also exerts a fine control on ARR1 levels at the TZ from the endodermis by sustaining gibberellin signals. From the endodermis, SCR controls the RGA REPRESSOR OF ga1-3 (RGA) DELLA protein stability throughout the root meristem, thus controlling ARR1 transcriptional activation at the TZ. This guarantees robustness and fineness to the control of ARR1 levels necessary to balance cell division to cell differentiation in sustaining coherent root growth. Therefore, this work advances the state of the art in the field of root meristem development by integrating the activity of three hormones, auxin, gibberellin, and cytokinin, under the control of different tissue-specific activities of a single root key regulator, SCR.

Intercellular signaling through trafficking of regulatory proteins is a widespread phenomenon in plants and can deliver positional information for the determination of cell fate. In the Arabidopsis root meristem, the cell fate determinant SHORT-ROOT (SHR), a GRAS domain transcription factor, acts as a signaling molecule from the stele to the adjacent layer to specify endodermal cell fate. Upon exiting the stele, SHR activates another GRAS domain transcription factor, SCARCROW (SCR), which, together with several BIRD/INDETERMINATE DOMAIN proteins, restricts movement of SHR to define a single cell layer of endodermis. Here we report that endodermal cell fate also requires the joint activity of both SCR and its closest homologue SCARECROW-LIKE23 (SCL23). We show that SCL23 protein moves with zonation-dependent directionality. Within the meristem, SCL23 exhibits short-ranged movement from ground tissue to vasculature. Away from the meristem, SCL23 displays long-range rootward movement into meristematic vasculature and a bidirectional radial spread, respectively. As a known target of SHR and SCR, SCL23 also interacts with SCR and SHR and can restrict intercellular outspread of SHR without relying on nuclear retention as SCR does. Collectively, our data show that SCL23 is a mobile protein that controls movement of SHR and acts redundantly with SCR to specify endodermal fate in the root meristem., (© 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.)

There is an increasing interest in complementing RNA-seq experiments with small-RNA (sRNA) expression data to obtain a comprehensive view of a transcriptome. Currently, two main experimental challenges concerning sRNA-seq exist: how to check the size distribution of isolated sRNAs, given the sensitive size-selection steps in the protocol; and how to normalize data between samples, given the low complexity of sRNA types. We here present two separate sets of synthetic RNA spike-ins for monitoring size-selection and for performing data normalization in sRNA-seq. The size-range quality control (SRQC) spike-in set, consisting of 11 oligoribonucleotides (10-70 nucleotides), was tested by intentionally altering the size-selection protocol and verified via several comparative experiments. We demonstrate that the SRQC set is useful to reproducibly track down biases in the size-selection in sRNA-seq. The external reference for data-normalization (ERDN) spike-in set, consisting of 19 oligoribonucleotides, was developed for sample-to-sample normalization in differential-expression analysis of sRNA-seq data. Testing and applying the ERDN set showed that it can reproducibly detect differential expression over a dynamic range of 2(18). Hence, biological variation in sRNA composition and content between samples is preserved while technical variation is effectively minimized. Together, both spike-in sets can significantly improve the technical reproducibility of sRNA-seq., (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objectives: We assessed the association between herpes zoster (HZ) and herpes simplex (HS) occurrence whilst controlling for risk factors of HZ., Methods: Using a Belgian general practitioner network, a retrospective cohort study with 3736 HZ patients and 14,076 age-gender-practice matched controls was performed, covering over 1.5 million patient-years. Multiple logistic regression was used with HZ as outcome and several diagnoses (malignancy, depression, diabetes mellitus, auto-immune diseases, asthma, multiple sclerosis, HIV, fractures), medications (systemic corticosteroids, biologicals, vaccination), HS and other infections as variables., Results: HS was significantly associated with HZ for all analysed time intervals (up to five years) post HZ (OR of 3.51 [2.09 5.88] 95%CI one year post HZ) and to a lesser extent for time ranges pre HZ. Registration of other infections was significantly associated with HZ in all time intervals pre and post HZ (OR up to 1.37). Malignancy up to five years pre HZ, depression up to one year pre or post HZ, fractures up to two years pre HZ, asthma, auto-immune diseases, and immunosuppressive medication one year pre or post HZ were also associated with HZ., Conclusions: HZ and HS occurrences are significantly associated and potentially share a common susceptibility beyond the known risk factors., (Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

A critical issue in development is the coordination of the activity of stem cell niches with differentiation of their progeny to ensure coherent organ growth. In the plant root, these processes take place at opposite ends of the meristem and must be coordinated with each other at a distance. Here, we show that in Arabidopsis, the gene SCR presides over this spatial coordination. In the organizing center of the root stem cell niche, SCR directly represses the expression of the cytokinin-response transcription factor ARR1, which promotes cell differentiation, controlling auxin production via the ASB1 gene and sustaining stem cell activity. This allows SCR to regulate, via auxin, the level of ARR1 expression in the transition zone where the stem cell progeny leaves the meristem, thus controlling the rate of differentiation. In this way, SCR simultaneously controls stem cell division and differentiation, ensuring coherent root growth., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The plant basic body plan is laid down during embryogenesis. All post-embryonic development has its origin in the stem cells located in niches in the heart of the shoot and root meristems. Creating the root niche requires auxin dependent patterning cues that provide positional information in combination with parallel inputs to specify and maintain the root stem cell niche from embryogenesis onwards. Once established, the architecture of the root niche differs from that in the shoot but recent findings reveal a conserved module for stem cell control. Important for stem cell maintenance is the balance between cell division and differentiation. Dealing with the environment is the biggest challenge for plants and that includes complete regeneration of stem cell systems upon damage. Here we will address these issues as we follow the formation, function and maintenance of the root stem cell niche during development.

A commercial assay for the measurement of the free thyroxine concentration in serum has been subjected to a change of method of calculation, together with a change of antibody. The clinical significance of both methods of calculation, before and after the change of antibody, has been investigated. Before the change of antibody the results of the original method of calculation were in slightly better agreement with the clinical data. After the change of antibody the results of the modified method of calculation were in better agreement with the clinical data.

Both total thyroxine and free thyroxine concentrations are measured in the Immophase free thyroxine assay. These total and free thyroxine results allow a prediction of the accessory concentrations of thyroxine-binding globulin (TBG). Since abnormal concentrations of TBG often cause problems in the evaluation of thyroid function, we evaluated the possibility of predicting these abnormal values from total and free thyroxine results. Two ways of predicting abnormal concentrations of TBG were evaluated on statistical grounds. The first method, a simple total thyroxine/free thyroxine ratio, proved to be better than the second method, which corrected for the influence of the other thyroxine binding proteins (result: a calculated concentration of TBG). The total thyroxine/free thyroxine ratio predicts abnormally low TBG values, below a ratio fo 4,000 (certainty 45%) and abnormally high TBG values, above a ratio of 6,400 (certainty 89%).