Changing plastid dynamics within early root and shoot apical meristem-derived tissue of A. thaliana

Whilst plastids are fundamental to many aspects of plant biology and the production of enhanced crop cultivars, research into the dynamics of non-green plastids has remained somewhat disregarded by the scientific community compared to chloroplasts. They are equally pivotal to normal plant development however, and are now increasingly becoming the focus of research made possible by genetic manipulation and reporter gene constructs. The total plastid content of all plant cells originates from small, undifferentiated plastids termed proplastids found within the meristematic regions of both root and shoot tissue. The cellular regulatory mechanisms controlling the development of plastids in young tissues are poorly understood, especially in the case of non-green plastids in roots. This investigation consequently aimed to elucidate the differences in plastid content, morphology and subcellular localization within epidermal cells derived from the root and shoot apical meristems (RAM and SAM respectively) of Arabidopsis thaliana. Quantification of non-green plastids was facilitated via the use of confocal laser scanning microscopy in conjunction with the expression of plastid-targeted green fluorescent protein driven by a constitutive promoter. Characterization of early seedling development and tissue diversification was also achieved by assessing epidermal cell size relative to developmental progression, ultimately facilitating comparative analyses of plastid dynamics on both a temporal and tissue-varietal basis. The number of plastids in epidermal cells within RAM-derived tissue was shown to increase across regions of cell division before being regulated throughout subsequent zones of elongation and maturing root tissue. In contrast, epidermal cells of the hypocotyl exhibit a more generalized increase in plastid number and less strict maintenance of cell plan area coverage during tissue expansion. The findings presented here suggest the functioning of distinct mechanisms regulating plastid division and growth in relation to cell size within shoot and root apical meristem-derived tissues

The industrious revolution, the industriousness discourse, and the development of modern economies

ABSTRACTThe idea of industriousness has been an ever-recurring issue since Max Weber launched it as a putative explanation of the advent of economic modernity. The notion of ‘industrious revolution’ has provoked a renewed flourishing of publications focusing on this issue. Although most historians agree on the emergence of industriousness in seventeenth-century Europe, there is no consensus regarding the chronology, hence the real causes, of this mental and discursive shift. This article emphasizes the problematic role played by literary evidences in these social and cultural models of diffusion of new consumer values and desires. It then establishes the timing of the emergence of the ‘industriousness discourse’ using an original approach to diffusion based both on the quantitative analysis of very large corpora and a close reading of seventeenth-century economic pamphlets and educational literature. It concludes first that there was not one but several competing discourses on industriousness. It then identifies two crucial hinges which closely match the chronology proposed by Allen and Muldrew, but refutes that championed by de Vries and McCloskey. The industrious revolution as described by these authors would have happened both too late to fit its intellectual roots and too early to signal the beginning of a ‘consumer revolution’.This work was supported by the Arts and Humanities Research CouncilThis is the author accepted manuscript. The final version is available from Cambridge University Press via https://doi.org/10.1017/S0018246X1300052

RNAG: a new Gibbs sampler for predicting RNA secondary structure for unaligned sequences

Motivation: RNA secondary structure plays an important role in the function of many RNAs, and structural features are often key to their interaction with other cellular components. Thus, there has been considerable interest in the prediction of secondary structures for RNA families. In this article, we present a new global structural alignment algorithm, RNAG, to predict consensus secondary structures for unaligned sequences. It uses a blocked Gibbs sampling algorithm, which has a theoretical advantage in convergence time. This algorithm iteratively samples from the conditional probability distributions P(Structure | Alignment) and P(Alignment | Structure). Not surprisingly, there is considerable uncertainly in the high-dimensional space of this difficult problem, which has so far received limited attention in this field. We show how the samples drawn from this algorithm can be used to more fully characterize the posterior space and to assess the uncertainty of predictions

Climatic history of the northeastern United States during the past 3000 years

Many ecosystem processes that influence Earth system feedbacks – vegetation growth, water and nutrient cycling, disturbance regimes – are strongly influenced by multidecadal- to millennial-scale climate variations that cannot be directly observed. Paleoclimate records provide information about these variations, forming the basis of our understanding and modeling of them. Fossil pollen records are abundant in the NE US, but cannot simultaneously provide information about paleoclimate and past vegetation in a modeling context because this leads to circular logic. If pollen data are used to constrain past vegetation changes, then the remaining paleoclimate archives in the northeastern US (NE US) are quite limited. Nonetheless, a growing number of diverse reconstructions have been developed but have not yet been examined together. Here we conduct a systematic review, assessment, and comparison of paleotemperature and paleohydrological proxies from the NE US for the last 3000 years. Regional temperature reconstructions (primarily summer) show a long-term cooling trend (1000 BCE–1700 CE) consistent with hemispheric-scale reconstructions, while hydroclimate data show gradually wetter conditions through the present day. Multiple proxies suggest that a prolonged, widespread drought occurred between 550 and 750 CE. Dry conditions are also evident during the Medieval Climate Anomaly, which was warmer and drier than the Little Ice Age and drier than today. There is some evidence for an acceleration of the longer-term wetting trend in the NE US during the past century; coupled with an abrupt shift from decreasing to increasing temperatures in the past century, these changes could have wide-ranging implications for species distributions, ecosystem dynamics, and extreme weather events. More work is needed to gather paleoclimate data in the NE US to make inter-proxy comparisons and to improve estimates of uncertainty in reconstructions

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

The Tyrosine Kinase Pyk-2/Raftk Regulates Natural Killer (Nk) Cell Cytotoxic Response, and Is Translocated and Activated upon Specific Target Cell Recognition and Killing

The compartmentalization of plasma membrane proteins has a key role in regulation of lymphocyte activation and development of immunity. We found that the proline-rich tyrosine kinase-2 (PYK-2/RAFTK) colocalized with the microtubule-organizing center (MTOC) at the trailing edge of migrating natural killer (NK) cells. When polyclonal NK cells bound to K562 targets, PYK-2 translocated to the area of NK–target cell interaction. The specificity of this process was assessed with NK cell clones bearing activatory or inhibitory forms of CD94/NKG2. The translocation of PYK-2, MTOC, and paxillin to the area of NK–target cell contact was regulated upon specific recognition of target cells through NK cell receptors, controlling target cell killing. Furthermore, parallel in vitro kinase assays showed that PYK-2 was activated in response to signals that specifically triggered its translocation and NK cell mediated cytotoxicity. The overexpression of both the wt and a dominant-negative mutant of PYK-2, but not ZAP-70 wt, prevented the specific translocation of the MTOC and paxillin, and blocked the cytotoxic response of NK cells. Our data indicate that subcellular compartmentalization of PYK-2 correlates with effective signal transduction. Furthermore, they also suggest an important role for PYK-2 on the assembly of the signaling complexes that regulate the cytotoxic response

Molecular biomarkers in the context of focal therapy for prostate cancer: Recommendations of a delphi consensus from the focal therapy society

BACKGROUND: Focal therapy (FT) for prostate cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localized PCa. METHODS: A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, 1) the current/present role; 2) the potential/future role; 3) the recommended features for future studies. Consensus was defined using a 70% agreement threshold. RESULTS: Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (N.=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (N.=3), a consensus on a partial agreement (N.=1), and a consensus on uncertainty (N.=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localized PCa. Research efforts in this field should be considered a priority. CONCLUSIONS: The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject

Radial velocity confirmation of a hot super-Neptune discovered by TESS with a warm Saturn-mass companion

We report the discovery and confirmation of the planetary system TOI-1288. This late G dwarf harbours two planets: TOI-1288 b and TOI-1288 c. We combine TESS space-borne and ground-based transit photometry with HARPS-N and HIRES high-precision Doppler measurements, which we use to constrain the masses of both planets in the system and the radius of planet b. TOI-1288~b has a period of $2.699835^{+0.000004}_{-0.000003}$ d, a radius of $5.24 \pm 0.09$ R$_\oplus$, and a mass of $42 \pm 3$ M$_\oplus$, making this planet a hot transiting super-Neptune situated right in the Neptunian desert. This desert refers to a paucity of Neptune-sized planets on short period orbits. Our 2.4-year-long Doppler monitoring of TOI-1288 revealed the presence of a Saturn-mass planet on a moderately eccentric orbit ($0.13^{+0.07}_{-0.09}$) with a minimum mass of $84 \pm 7$ M$_\oplus$ and a period of $443^{+11}_{-13}$ d. The 5 sectors worth of TESS data do not cover our expected mid-transit time for TOI-1288 c, and we do not detect a transit for this planet in these sectors.Comment: 16 pages, 17 figures, under review MNRA