North Pyrenean populations of <em>Megabunus diadema</em> (Fabricius, 1779) (Arachnida: Opiliones) are characterized by highly male-biased sex ratios

<em>Megabunus diadema</em> (Fabricius, 1779) is an Atlantic and European harvestman species characterized by a discontinuous distribution from Scandinavia to the Iberian Peninsula. With very few male individuals ever observed in the field until now, the biological uniqueness of the species lies in its reproduction mode, hitherto regarded as asexual, facultative parthenogenesis. Based on a large sample of 741 sexed individuals, the study indicates a sex ratio much higher than what was formerly known, equal to 65.58% of males. Locally varying from 0 to 100% (median 75.5% of males), the sex ratio depends indeed on the altitude and the phenological cycle: the proportion of males decreases with increasing altitude and increases gradually during the spring to reach a plateau in summer. By describing populations locally dominated by male individuals and providing new information on the spatial and temporal patterns of tertiary sex ratio, we question the currently admitted reproduction mode of the species which could be normally sexual, at least locally, rather than asexual. A distribution map of the species on the northern slope of the Pyrenees is provided for the first time. Our study also complements the distribution for the southern slopes of the Pyrenees and the rest of the Iberian Peninsula published recently by Merino-Sáinz et al. (2013).<br><br><em>Megabunus diadema</em> (Fabricius 1779) es una especie de opilión Atlántica y Europea, caracterizada por una distribución discontinua desde Escandinavia a la Península Ibérica. La singularidad biológica de la especie se encuentra en el modo de reproducción, la partenogénesis facultativa, hasta ahora considerada como asexual. De hecho, hasta el momento se han observado muy pocos individuos masculinos en el campo. Los resultados de este estudio muestran, sobre una amplia muestra (741 individuos sexuados), que la proporción de sexo masculino es muy superior a lo conocido hasta ahora (65%). Localmente este porcentaje puede variar entre 0 y 100% (mediana del 75,5% para los machos). Los resultados muestran que la proporción de sexos depende de la altitud y del ciclo fenológico: la proporción de machos disminuye con la altitud y aumenta gradualmente durante la primavera hasta llegar a una meseta en verano. Para describir las poblaciones dominadas localmente por individuos masculinos y proporcionar nueva información sobre los patrones espaciales y temporales de la proporción de sexos en poblaciones adultas, cuestionamos el modo de reproducción actualmente admitido de la especie que podría ser normalmente sexual, al menos localmente, en lugar de asexual. Se proporciona, por primera vez, un mapa de distribución de la especie en la vertiente norte de los Pirineos. Nuestro estudio también complementa el estudio publicado recientemente por Merino-Sáinz et al. (2013) sobre su distribución en la vertiente sur de los Pirineos y en el resto de la Península Ibérica

Cytohistological and cytochemical features of the seeds of Malus domestica Borkh exposed to spring frosts

AbstractMalus domestica Borkh cv. Golden Delicious trees, exposed to spring frost, showed the occurrence of seeds with white (W), spotted (S) and black (B) integuments, with a different distribution, amount and damage in shedding and non-shedding fruits at several times after anthesis. While B seeds were completely degenerated, the S seeds showed hystological and cytochemical features that included a precocious embryo development stage, an embryonal cells shrinkage, an absence of reserves in the suspensor, endosperm and integuments, and a probable block of the routing of reserves, as a consequence of spring frost damages. All these features are the same occurring in seeds undergoing to natural abscission phenomenon and in the W seeds of shedding fruits observed in previous years. The S seeds damage is certainly attributable to meteorological events, because the S seeds were never found until the occurrence of the spring frosts. On the contrary, the damage in the W seeds, which do not show external symptom..

Differential Contributions of Conformation Extension and Domain Unfolding to Properties of Fibronectin Nanotextiles

Fibronectin (FN) textiles are built as nanometer-thick fabrics. When uniaxially loaded, these fabrics exhibit a distinct threshold between elastic and plastic deformation with increasing stretch. Fabric mechanics are modeled using an eight-chain network and two-state model, revealing that elastic properties of FN depend on conformational extension of the protein and that plastic deformation depends on domain unfolding. Our results suggest how the molecular architecture of a molecule can be exploited for designer mechanical properties of a bulk material.Engineering and Applied Science

Nerve growth factor improves the muscle regeneration capacity of muscle stem cells in dystrophic muscle.

Researchers have attempted to use gene- and cell-based therapies to restore dystrophin and alleviate the muscle weakness that results from Duchenne muscular dystrophy (DMD). Our research group has isolated populations of muscle-derived stem cells (MDSCs) from the postnatal skeletal muscle of mice. In comparison with satellite cells, MDSCs display an improved transplantation capacity in dystrophic mdx muscle that we attribute to their ability to undergo long-term proliferation, self-renewal, and multipotent differentiation, including differentiation toward endothelial and neuronal lineages. Here we tested whether the use of nerve growth factor (NGF) improves the transplantation efficiency of MDSCs. We used two methods of in vitro NGF stimulation: retroviral transduction of MDSCs with a CL-NGF vector and direct stimulation of MDSCs with NGF protein. Neither method of NGF treatment changed the marker profile or proliferation behavior of the MDSCs, but direct stimulation with NGF protein significantly reduced the in vitro differentiation ability of the cells. NGF stimulation also significantly enhanced the engraftment efficiency of MDSCs transplanted within the dystrophic muscle of mdx mice, resulting in the regeneration of numerous dystrophin-positive muscle fibers. These findings highlight the importance of NGF as a modulatory molecule, the study of which will broaden our understanding of its biologic role in the regeneration and repair of skeletal muscle by musclederived cells

Real-World Apremilast Use for Treatment of Plaque Psoriasis in Italy: Patient Perspective, Characteristics, and Clinical Outcomes from the DARWIN Study

IntroductionWhile several european studies have reported real-world apremilast use, patient-perceived benefits, and treatment satisfaction, local reimbursement criteria for apremilast vary and data from Italy are limited.methodsThe cross-sectional DARWIN study enrolled consecutive patients who had initiated apremilast for plaque psoriasis 6 (+/- 1) months prior to enrolment at a single visit across 24 Italian dermatological sites. disease severity was assessed using body surface area (BSA) and physician global assessment (PGA). patient-reported outcomes assessed 6 (+/- 1) months after apremilast initiation were dermatology life quality Index (DLQI), patient benefit Index (PBI), and 9-item treatment satisfaction questionnaire for medication (TSQM-9).ResultsOf 184 patients enrolled between July 2019 and January 2021, 180 were included in the analysis. at apremilast initiation, median (25th-75th percentile) time since psoriasis diagnosis was 8.6 (3.2-22.2) years; median BSA, 10.0% (5.0-16.0); mean (standard seviation, SD) DLQI total score, 13.5 (8.0). over half (54.9%) of patients with available data reported psoriasis had a very or extremely large effect on their quality of life (QoL); half reported itching (50.6%) and/or special areas involvement (50.0%). most (73.9%) had comorbidities and were biologic-naive (81.5%). the most common reasons for initiating apremilast were lack of efficacy of previous treatment (56.7%) and contraindications to other treatments (44.4%). At 6 (+/- 1) months, most patients were continuing apremilast and/or reported a global PBI score &gt;= 1 (minimum clinical benefit) (86.1% and 90.0%, respectively); approximately half achieved BSA &lt;= 3% and/or DLQI total score &lt;= 5 (47.1% and 48.5%); 18.8% achieved PGA = 0; mean (SD) TSQM-9 global treatment satisfaction score was 59.0 (24.8). apremilast was well tolerated; no new safety signals were identified .conclusions patients treated with apremilast for 6 months in Italian clinical practice reported improved QoL, clinically relevant improvements in symptoms, high treatment satisfaction, and high treatment persistence. our data indicate apremilast is a valuable treatment option for moderate plaque psoriasis. study registration clinical trials.gov identifier, NCT04031027

Involvement of MAF/SPP1 axis in the development of bone marrow fibrosis in PMF patients

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hyperplastic megakaryopoiesis and myelofibrosis. We recently described the upregulation of MAF (v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog) in PMF CD34+ hematopoietic progenitor cells (HPCs) compared to healthy donor. Here we demonstrated that MAF is also upregulated in PMF compared with the essential thrombocytemia (ET) and polycytemia vera (PV) HPCs. MAF overexpression and knockdown experiments shed some light into the role of MAF in PMF pathogenesis, by demonstrating that MAF favors the megakaryocyte and monocyte/macrophage commitment of HPCs and leads to the increased expression of proinflammatory and profibrotic mediators. Among them, we focused our further studies on SPP1 and LGALS3. We assessed SPP1 and LGALS3 protein levels in 115 PMF, 47 ET and 24 PV patients plasma samples and we found that SPP1 plasma levels are significantly higher in PMF compared with ET and PV patients. Furthermore, in vitro assays demonstrated that SPP1 promotes fibroblasts and mesenchymal stromal cells proliferation and collagen production. Strikingly, clinical correlation analyses uncovered that higher SPP1 plasma levels in PMF patients correlate with a more severe fibrosis degree and a shorter overall survival. Collectively our data unveil that MAF overexpression contributes to PMF pathogenesis by driving the deranged production of the profibrotic mediator SPP1

Deducing the source and composition of rare earth mineralising fluids in carbonatites: insights from isotopic (C, O, 87Sr/86Sr) data from Kangankunde, Malawi

This is the final version of the article. Available from Springer Verlag via the DOI in this record.Carbonatites host some of the largest and highest grade rare earth element (REE) deposits but the composition and source of their REE-mineralising fluids remains enigmatic. Using C, O and 87Sr/86Sr isotope data together with major and trace element compositions for the REE-rich Kangankunde carbonatite (Malawi), we show that the commonly observed, dark brown, Fe-rich carbonatite that hosts REE minerals in many carbonatites is decoupled from the REE mineral assemblage. REE-rich ferroan dolomite carbonatites, containing 8–15 wt% REE2O3, comprise assemblages of monazite-(Ce), strontianite and baryte forming hexagonal pseudomorphs after probable burbankite. The 87Sr/86Sr values (0.70302–0.70307) affirm a carbonatitic origin for these pseudomorph-forming fluids. Carbon and oxygen isotope ratios of strontianite, representing the REE mineral assemblage, indicate equilibrium between these assemblages and a carbonatite-derived, deuteric fluid between 250 and 400 °C (δ18O + 3 to + 5‰VSMOW and δ13C − 3.5 to − 3.2‰VPDB). In contrast, dolomite in the same samples has similar δ13C values but much higher δ18O, corresponding to increasing degrees of exchange with low-temperature fluids (< 125 °C), causing exsolution of Fe oxides resulting in the dark colour of these rocks. REE-rich quartz rocks, which occur outside of the intrusion, have similar δ18O and 87Sr/86Sr to those of the main complex, indicating both are carbonatite-derived and, locally, REE mineralisation can extend up to 1.5 km away from the intrusion. Early, REE-poor apatite-bearing dolomite carbonatite (beforsite: δ18O + 7.7 to + 10.3‰ and δ13C −5.2 to −6.0‰; 87Sr/86Sr 0.70296–0.70298) is not directly linked with the REE mineralisation.This project was funded by the UK Natural Environment Research Council (NERC) SoS RARE project (NE/M011429/1) and by NIGL (NERC Isotope Geoscience Laboratory) Project number 20135

Experimental Demonstration of Attosecond Pump-Probe Spectroscopy with an X-ray Free-Electron Laser

Pump-probe experiments with sub-femtosecond resolution are the key to understanding electronic dynamics in quantum systems. Here we demonstrate the generation and control of sub-femtosecond pulse pairs from a two-colour X-ray free-electron laser (XFEL). By measuring the delay between the two pulses with an angular streaking diagnostic, we characterise the group velocity of the XFEL and demonstrate control of the pulse delay down to 270 as. We demonstrate the application of this technique to a pump-probe measurement in core-excited para-aminophenol. These results demonstrate the ability to perform pump-probe experiments with sub-femtosecond resolution and atomic site specificity.Comment: 55 pages, main manuscript (5 figures) + supplementary materials (25 figures), 30 figures total. Submitted to Nature Photonic