Juvenile hormone biosynthesis in adult Blattella germanica requires nuclear receptors Seven-up and FTZ-F1

In insects, the transition from juvenile development to the adult stage is controlled by juvenile hormone (JH) synthesized from the corpora allata (CA) glands. Whereas a JH-free period during the last juvenile instar triggers metamorphosis and the end of the growth period, the reappearance of this hormone after the imaginal molt marks the onset of reproductive adulthood. Despite the importance of such transition, the regulatory mechanism that controls it remains mostly unknown. Here, using the hemimetabolous insect Blattella germanica, we show that nuclear hormone receptors Seven-up-B (BgSvp-B) and Fushi tarazu-factor 1 (BgFTZ-F1) have essential roles in the tissue-and stage-specific activation of adult CA JH-biosynthetic activity. Both factors are highly expressed in adult CA cells. Moreover, RNAi-knockdown of either BgSvp-B or BgFTZ-F1 results in adult animals with a complete block in two critical JH-dependent reproductive processes, vitellogenesis and oogenesis. We show that this reproductive blockage is the result of a dramatic impairment of JH biosynthesis, due to the CA-specific reduction in the expression of two key JH biosynthetic enzymes, 3-hydroxy-3-methylglutaryl coenzyme A synthase-1 (BgHMG-S1) and HMG-reductase (BgHMG-R). Our findings provide insights into the regulatory mechanisms underlying the specific changes in the CA gland necessary for the proper transition to adulthood.Support for this research was provided by the Spanish MINECO (grants BFU2009-10571 and CGL2014-55786-P to D.M. and CGL2012-36251 and CGL2015-64727-P to X.B.) and by the Catalan Government (2014 SGR 619 to D.M., J.L.M. and X.B.). The research has also benefited from FEDER funds. F.B.-C. is a recipient of a pre-doctoral research Grant from the MICINN. C.N. is a recipient of a postdoctoral research grant from CSIC. O.M. is recipient of a pre-doctoral research grant from Generalitat de Catalunya.Peer Reviewe

Measurement of top-pair cross section and top-quark mass in the di-lepton and full-hadronic channels with CMS

This note describes the selection and reconstruction of top-pair events with the CMS detector at the LHC, and the determination of the top-quark mass. Two of the three main channels, classified by the decay of the W boson arising in top decay, are considered here: di-lepton and fully hadronic \ttbar events. The performance of the selections, the resulting cross section measurements, and the mass reconstruction accuracy are evaluated based on a detailed simulation of the CMS detector

The Impact of Crystal Light Yield Non-Proportionality on a Typical Calorimetric Space Experiment: Beam Test Measurements and Monte Carlo Simulations

Calorimetric space experiments were employed for the direct measurements of cosmic-ray spectra above the TeV region. According to several theoretical models and recent measurements, relevant features in both electron and nucleus fluxes are expected. Unfortunately, sizable disagreements among the current results of different space calorimeters exist. In order to improve the accuracy of future experiments, it is fundamental to understand the reasons of these discrepancies, especially since they are not compatible with the quoted experimental errors. A few articles of different collaborations suggest that a systematic error of a few percentage points related to the energy-scale calibration could explain these differences. In this work, we analyze the impact of the nonproportionality of the light yield of scintillating crystals on the energy scale of typical calorimeters. Space calorimeters are usually calibrated by employing minimal ionizing particles (MIPs), e.g., nonshowering proton or helium nuclei, which feature different ionization density distributions with respect to particles included in showers. By using the experimental data obtained by the CaloCube collaboration and a minimalist model of the light yield as a function of the ionization density, several scintillating crystals (BGO, CsI(Tl), LYSO, YAP, YAG and BaF2) are characterized. Then, the response of a few crystals is implemented inside the Monte Carlo simulation of a space calorimeter to check the energy deposited by electromagnetic and hadronic showers. The results of this work show that the energy scale obtained by MIP calibration could be affected by sizable systematic errors if the nonproportionality of scintillation light is not properly taken into account

Studying the Impact of Different Field Environmental Conditions on Seed Quality of Quinoa: The Case of Three Different Years Changing Seed Nutritional Traits in Southern Europe

Chenopodium quinoa Willd (quinoa) has acquired an increased agronomical and nutritional relevance due to the capacity of adaptation to different environments and the exceptional nutritional properties of their seeds. These include high mineral and protein contents, a balanced amino acid composition, an elevated antioxidant capacity related to the high phenol content, and the absence of gluten. Although it is known that these properties can be determined by the environment, limited efforts have been made to determine the exact changes occurring at a nutritional level under changing environmental conditions in this crop. To shed light on this, this study aimed at characterizing variations in nutritional-related parameters associated with the year of cultivation and different genotypes. Various nutritional and physiological traits were analyzed in seeds of different quinoa cultivars grown in the field during three consecutive years. We found differences among cultivars for most of the nutritional parameters analyzed. It was observed that the year of cultivation was a determinant factor in every parameter studied, being 2018 the year with lower yields, germination rates, and antioxidant capacity, but higher seed weights and seed protein contents. Overall, this work will greatly contribute to increase our knowledge of the impact of the environment and genotype on the nutritional properties of quinoa seeds, especially in areas that share climatic conditions to Southern Europe.This work was supported by the Ministerio de Ciencia e Innovación (MICINN, Spain) (PID2019-105748RA-I00), the Madrid Government (Comunidad de Madrid-Spain) under the Multiannual Agreement with Universidad Autónoma de Madrid in the line of action encouraging youth research doctors, in the context of the V PRICIT (Regional Programme of Research and Technological Innovation) (SI1/PJI/2019-00124), the CYTED (ValSe-Food 119RT0567), the FPI UAM Fellowship Programme 2019 (to SG-R), and the Ramón y Cajal Programme 2019 (to MR).Peer reviewe

Long-Term Outcomes After Autologous Versus Allogeneic Stem Cell Transplantation in Molecularly-Stratified Patients With Intermediate Cytogenetic Risk Acute Myeloid Leukemia: A PETHEMA Study

PETHEMA (Programa Español de Tratamientos en Hematología) and GETH (Grupo Espa~nol de Trasplante Hematopoyético y Terapia Celular) Cooperative GroupsAcute myeloid leukemia (AML) with intermediate risk cytogenetics (IRcyto) comprises a variety of biological entities with distinct mutational landscapes that translate into differential risks of relapse and prognosis. Optimal postremission therapy choice in this heterogeneous patient population is currently unsettled. In the current study, we compared outcomes in IRcyto AML recipients of autologous (autoSCT) (n = 312) or allogeneic stem cell transplantation (alloSCT) (n = 279) in first complete remission (CR1). Molecular risk was defined based on CEBPA, NPM1, and FLT3-ITD mutational status, per European LeukemiaNet 2017 criteria. Five-year overall survival (OS) in patients with favorable molecular risk (FRmol) was 62% (95% confidence interval [CI], 50-72) after autoSCT and 66% (95% CI, 41-83) after matched sibling donor (MSD) alloSCT (P = .68). For patients of intermediate molecular risk (IRmol), MSD alloSCT was associated with lower cumulative incidence of relapse (P < .001), as well as with increased nonrelapse mortality (P = .01), as compared to autoSCT. The 5-year OS was 47% (95% CI, 34-58) after autoSCT and 70% (95% CI, 59-79) after MSD alloSCT (P = .02) in this patient subgroup. In a propensity-score matched IRmol subcohort (n = 106), MSD alloSCT was associated with superior leukemia-free survival (hazard ratio [HR] 0.33, P = .004) and increased OS in patients alive 1 year after transplantation (HR 0.20, P = .004). These results indicate that, within IRcyto AML in CR1, autoSCT may be a valid option for FRmol patients, whereas MSD alloSCT should be the preferred postremission strategy in IRmol patients.Supported by a Río Hortega academic clinical fellowship (CM19/00194) from the Instituto de Salud Carlos III, Spain (E.R.A.). Additional funding has been provided by CIBERONC grants to J.P.S. (CB16/12/00480), M.M.S. (CB16/12/00369) and B.V. (CB16/12/00233)

SIAMOC position paper on gait analysis in clinical practice: General requirements, methods and appropriateness. Results of an Italian consensus conference

Gait analysis is recognized as a useful assessment tool in the field of human movement research. However, doubts remain on its real effectiveness as a clinical tool, i.e. on its capability to change the diagnostic-therapeutic practice. In particular, the conditions in which evidence of a favorable cost-benefit ratio is found and the methodology for properly conducting and interpreting the exam are not identified clearly. To provide guidelines for the use of Gait Analysis in the context of rehabilitation medicine, SIAMOC (the Italian Society of Clinical Movement Analysis) promoted a National Consensus Conference which was held in Bologna on September 14th, 2013. The resulting recommendations were the result of a three-stage process entailing i) the preparation of working documents on specific open issues, ii) the holding of the consensus meeting, and iii) the drafting of consensus statements by an external Jury. The statements were formulated based on scientific evidence or experts' opinion, when the quality/quantity of the relevant literature was deemed insufficient. The aim of this work is to disseminate the consensus statements. These are divided into 13 questions grouped in three areas of interest: 1) General requirements and management, 2) Methodological and instrumental issues, and 3) Scientific evidence and clinical appropriateness. SIAMOC hopes that this document will contribute to improve clinical practice and help promoting further research in the field

Expression of juvenile hormone acid O-methyltransferase and juvenile hormone synthesis in Blattella germanica

Juvenile hormone (JH), a sesquiterpenoid synthetized by the insect corpora allata (CA), plays critical roles in metamorphosis and reproduction. Penultimate or last step of JH synthesis is catalyzed by juvenile hormone acid O-methyltransferase (JHAMT). Here we report the cloning and expression analysis of the JHAMT orthologue in the cockroach, Blattella germanica (L.) (BgJHAMT). BgJHAMT is mainly expressed in CA, with only expression traces in ovary. Three different isoforms, differing in the 3′-UTR sequence, were identified. Isoform A shows between 35 and 65 times higher expression than B and C in CA from penultimate nymphal instar and adult females. RNAi-triggered knock down of BgJHAMT produces a dramatic reduction of JH synthesis, concomitant with a decrease of fat body vitellogenin expression and basal follicle length. BgJHAMT mRNA levels in CA of females along the gonadotrophic cycle parallel, with a slight advancement, JH synthesis profile. BgJHAMT mRNA levels were reduced in starved females and in females in which we reduced nutritional signaling by knocking down insulin receptor and target of rapamycin (TOR). Results show that conditions that modify JH synthesis in adult B. germanica females show parallel changes of BgJHAMT mRNA levels and that the JH-specific branch of the JH synthesis pathway is regulated in the same way as the mevalonate branch. Furthermore, we demonstrate that nutrition and its signaling through the insulin receptor and TOR pathways are essential for activating BgJHAMT expression, which suggests that this enzyme can be a checkpoint for the regulation of JH production in relation to nutritional status.This work was supported by grants BFU2010-15906 (Spanish Ministry of Science and Innovation (MICINN)), CGL2016-76011-R (Spanish Ministry of Economy and Competitiveness (MINECO) and FEDER) and 2014-SGR-619 (Secretaria d’Universitats i Recerca, Catalan Goverment) to J.L.M.Peer reviewe

Regulation of JH biosynthesis enzymes by nuclear hormone receptors in Blattella germanica

Trabajo presentado en la 9th International Conference on Juvenile Hormones, celebrada en York (UK) del 5 al 10 de agosto de 2007.N

Regulation of insulin-like peptide expression in adult Blattella germanica females

The insulin-IGF-signalling (IIS) pathway regulates key processes in metazoans. The pathway is activated through the binding of the ligands, which in insects are usually referred to as insulin-like peptides (ILPs), to a class of receptor tyrosine kinases, the insect insulin receptor. To study the pathway regulation, it is therefore essential to understand how ILPs are produced and released. In this study we analysed the factors that regulate the expression of the seven ILPs (BgILPs) expressed in adult females of the German cockroach, Blattella germanica. The results showed that the starvation-induced expression reduction of brain BgILP3, 5 and 6 and fat body BgILP7 is not due to reduced juvenile hormone (JH) or decreased TOR pathway activity. In addition, depletion of FoxO in starved females did not correct the low levels of these BgILPs, but even reduced further BgILP5 expression, indicating the need to maintain certain basal levels of BgILP5 even during starvation. Furthermore, JH promoted increased BgILP5 and decreased BgILP3 expression in the brain, an effect that required Methoprene-tolerant (Met), the JH receptor, but not Krüppel homolog 1 (Kr-h1), the main JH transducer. On the other hand, JH inhibited the expression of BgILP7 in the fat body, although in this case, the action required both Met and Kr-h1. In addition, JH reduction treatments produced a decrease in the expression of the insulin receptor in the fat body, which suggests an increase in IIS. The results show a peculiar regulation of ILP expression in adult B. germanica females, which is clearly different than that seen in other species. This is understandable given that gene duplications in recent clades have resulted in different sets of ILP genes, involving substantial changes in gene regulatory networks.This work was supported by Agencia Estatal de Investigación (grant number PID2019-104483GB-I00/AEI/10.13039/501100011033), Secretaria d’Universitats i Recerca, Catalan Goverment (grant number 2017 SGR 1030) and Agencia Estatal Consejo Superior de Investigaciones Científicas (grant number 2019AEP029).Peer reviewe

Ecdysone meets juvenile hormone: nuclear receptors seven-up and FTZ-F1 control juvenile hormone biosynthesis during hemimetabolan metamorphosis

Trabajo presentado en el Insect Hormones (19th Ecdysone) International Workshop, celebrado en Minneapolis del 21 al 26 de julio de 2013.Ecdysone and juvenile hormone (JH) are critical coordinators of normal developmental transitions in insects. In the hemimetabolous insect Blattella germanica, as in all insects, the presence of JH during juvenile development ensures that the molt will produce another juvenile instar, whereas the natural fall of this hormone in the final instar leads to the imaginal molt. Interestingly, a characteristic endocrine feature of the final nymphal instar of B. germanica is the reappearance of JH at the molt to the adult stage, as this hormone has also a major role in the regulation of reproduction. Thus, the corpora allata, whose biosynthetic activity has been impaired during the final nymphal stage, is reactivated to synthesize JH during the adult stage. Unfortunately, the mechanism that accounts for the re-­‐induction of the corpora allata biosynthetic activity at the adult molt has not been identified. Here, we show that two nuclear hormone receptors expressed in the corpora allata, BgFTZ-­‐F1 (whose expression in the gland is tightly controlled by the ecdysone-­‐dependent transcriptional cascade of nuclear hormone receptors) and seven-­‐up (BgSvp), control the stage-­‐ specific activation of the JH-­‐biosynthetic activity of the gland during the nymphal to adult transition. Animals with reduced levels of BgSvp or BgFTZ-­‐F1 presented a dramatic reduction in JH biosynthesis due to the lack of activation of several key JH-­‐biosynthesis enzymes, such as HMG-­‐CoA Synthase and HMG-­‐CoA reductase. Finally, we show that this complex cross-­‐regulatory interplay between BgSvp and BgFTZ-­‐F1 also controls JH biosynthesis during the successive gonadotrophic cycles of B. germanica.Peer Reviewe