Miracle-dz/UniFAR-FTUs huggingface dataset:
A G protein–coupled receptor mediates neuropeptide-induced oocyte maturation in the jellyfish Clytia

The reproductive hormones that trigger oocyte meiotic maturation and release from the ovary vary greatly between animal species. Identification of receptors for these Maturation Inducing Hormones (MIHs), and understanding how they initiate the largely conserved maturation process, remain important challenges. In hydrozoan cnidarians including the jellyfish Clytia hemisphaerica, MIH comprises neuropeptides released from somatic cells of the gonad. We identified the receptor (MIHR) for these MIH neuropeptides in Clytia using cell culture-based “deorphanization” of candidate oocyte-expressed GPCRs. MIHR mutant jellyfish generated using CRISPR-Cas9 had severe defects in gamete development or in spawning both in males and females. Female gonads, or oocytes isolated from MIHR mutants, failed to respond to synthetic MIH. Treatment with the cAMP analogue 5’Br-cAMP to mimic cAMP rise at maturation onset rescued meiotic maturation and spawning. Injection of inhibitory antibodies to GαS into wild type oocytes phenocopied the MIHR mutants. These results provide the molecular links between MIH stimulation and meiosis initiation in hydrozoan oocytes. Molecular phylogeny grouped Clytia MIHR with a subset of bilaterian neuropeptide receptors including Neuropeptide Y, Gonadotropin Inhibitory Hormone, pyroglutamylated RFamide and Luqin, all upstream regulators of sexual reproduction. This identification and functional characterisation of a cnidarian peptide GPCR advances our understanding of oocyte maturation initiation and sheds light on the evolution of neuropeptide-hormone systems.
The complete mitochondrial genome of Poecilia formosa (Poecilia, Cyprinodontidae) and phylogenetic studies of cyprinodontiformes

Abstract We report the complete mitochondrial genome sequence of Poecilia formosa. The genome is found to be 16636 bp in length and has a base composition of A (29.59%), G (14.61%), C (28.26%), and T (27.54%). Similar to other Poecilia species, it contains a typically conserved structure including 13 protein-coding genes, 2 rRNA genes, 1 control region (D-loop), and 22tRNA genes. The proportion of coding sequences with a total length of 11,533 bp is 69.33%, which encodes 3837 amino acids. All protein-coding genes started with Met, ND1, CO1, ATP8, ATP6, CO3, ND4L, ND5, ND6 and CytB ended by TAA as a stop codon, ND2 and ND3 ended by TAG as a stop codon, CO3 and ND4 ended by a single T. The lengths of 12S ribosomal RNA is 948 bp, ranging from 70 bp to 1018 bp, and the lengths of 16S ribosomal RNA is 1674 bp, ranging from 1090 bp to 2764 bp. The length of control region is 879 bp, ranging from 15757 bp to 16636 bp, respectively. The complete mitochondrial genome sequence provided here would be useful for further understanding the evolution of ratite and conservation genetics of Poecilia formosa.
Suppressor mutations in Mecp2-null mice reveal that the DNA damage response is key to Rett syndrome pathology

Mutations in X-linked methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome (RTT). We carried out a genetic screen for secondary mutations that improved phenotypes in Mecp2/Y mice after mutagenesis with N-ethyl-N-nitrosourea (ENU), aiming to identify potential therapeutic entry points. Here we report the isolation of 106 founder animals that show suppression of Mecp2-null traits from screening 3,177 Mecp2/Y genomes. Using exome sequencing, genetic crosses and association analysis, we identify 33 candidate genes in 30 of the suppressor lines. A network analysis shows that 61% of the candidate genes cluster into the functional categories of transcriptional repression, chromatin modification or DNA repair, delineating a pathway relationship with MECP2. Many mutations lie in genes that are predicted to modulate synaptic signaling or lipid homeostasis. Surprisingly, mutations in genes that function in the DNA damage response (DDR) also improve symptoms in Mecp2/Y mice. The combinatorial effects of multiple loci can be resolved by employing association analysis. One line, which was previously reported to carry a suppressor mutation in a gene required for cholesterol synthesis, Sqle, carries a second mutation in retinoblastoma binding protein 8 (Rbbp8 or CtIP), which regulates a DDR choice in double stranded break (DSB) repair. Cells from Mecp2/Y mice have increased DSBs, so this finding suggests that the balance between homology directed repair and non-homologous end joining is important for neuronal cells. In this and other lines, the presence of two suppressor mutations confers better symptom improvement than one locus alone, suggesting that combination therapies could be effective in RTT.
Impact of small RNAs in retrograde signalling pathways in Arabidopsis thaliana

Chloroplast perturbations activate retrograde signalling pathways causing dynamic changes of gene expression. Besides transcriptional control of gene expression different classes of small non-coding RNAs (sRNAs) act in gene expression control, but comprehensive analyses regarding their role in retrograde signalling is lacking. We performed sRNA profiling in response to norflurazon (NF) that provokes retrograde signals in A. thaliana wild type and the two retrograde signalling mutants gun1 and gun5. The RNA samples were also used for mRNA and long non-coding RNA (lncRNA) profiling to link altered sRNA levels to changes of their cognate target RNAs. We identified 122 sRNAs from all known sRNA classes that were responsive to NF in wild type. Strikingly, 140 and 213 sRNAs were found to be differentially regulated in both mutants indicating a retrograde control of these sRNAs. Concomitant with the changes in sRNA expression we detected about 1500 differentially expressed mRNAs in the NF treated wild type and around 900 and 1400 mRNAs that were differentially regulated in the gun1 and gun5 mutant with a high proportion (~30%) of genes encoding plastid proteins. Furthermore, around 20% of predicted miRNA targets code for plastid localised proteins. The analyses of sRNA-target pairs identified pairs with an anticorrelated expression as well pairs showing other expressional relations pointing to a role of sRNAs in balancing transcriptional changes upon retrograde signals. Based on the comprehensive changes in sRNA expression we assume a considerable impact of sRNAs in retrograde-dependent transcriptional changes to adjust plastidic and nuclear gene expression. Significance statement Perturbations of plastid functions trigger retrograde signalling to adjust plastidic and nuclear gene expression, however, the role of small non-coding RNAs acting as regulators in these pathways is not well understood. We analysed small non-coding RNA expression in response to retrograde signals in A. thaliana wild type and two retrograde signalling mutants and identified members of all known small non-coding RNA classes pointing to a functional role of these RNA classes in retrograde pathways.
PHARMACOKINETIC STUDY OF PROGESTERONE CAPSULES IN POST MENOPAUSAL FEMALES OF INDIA UNDER FASTING CONDITION

Summary The study was conducted to assess the pharmacokinetics of micronized progesterone administered in the capsule form. Ten post-menopausal females of India, with a mean age of 51.50 years, volunteered to participate in the study. The pharmacokinetics of 200 mg of progesterone evaluated by validated Liquid Chromatography Mass Sepectroscopy-Mass spectroscopy (LCMS-MS) method. After the initial administration of 200 mg, a mean serum Cmax of 3.59±0.66 was reached at a tmax of 3.50±0.59. The terminal half-life (t 1 /2) was 7.09±2.52. Micronized progesterone given as a capsule is well tolerated, safe and an easily administered.
Title: Real-life use of inhaled corticosteroids in COPD patients vs. GOLD proposals: a paradigm shift in GOLD 2011? Authors:

Affiliations: 1 Service de Pneumologie, Hôpital Cochin, AP-HP and Université Paris Descartes, Sorbonne Paris Cité, Paris, France 2 Service de Pneumologie, Hôpital Maison Blanche CHU de Reims – Reims France 3 Service de Pneumologie, Hôpital Bichat, AP-HP, Paris, France 4 Service de Pneumologie, Hôpital Pontchaillou, Rennes, France 5 Service de Pneumologie, Hôpital Gabriel Montpied, CHU Clermont-Ferrand, France 6 Département des Maladies Respiratoires, AP-HM, Aix Marseille Université, Marseille, France 7 Service de Pneumologie, CHU Saint Etienne, France 8 Clinique des voies respiratoires Hôpital Larrey, Toulouse, France 9 Service de pneumologie, Hôpital de la Croix Rousse, Lyon, France 10 EFFI-STAT, Paris, France 11 Service de Pneumologie, Hôpital Calmette, Lille, France
A Distinctive Pattern of Hippocampal-Prefrontal Cortical Network Activity during Stress Predicts Learned Resistance

The perception of control over a stressful experience may determine its impacts and generate resistance against future stressors. Although the medial prefrontal cortex (mPFC) and the hippocampus are implicated in the encoding of stressor controllability, the neural dynamics underlying this process are unknown. Here, we recorded CA1 and mPFC neural activities in rats during the exposure to controllable, uncontrollable, or no shocks, and investigated electrophysiological predictors of escape performance upon exposure to subsequent uncontrollable shocks. We were able to accurately discriminate stressed from non-stressed animals and predict resistant or helpless individuals based on neural oscillatory dynamics. We identified a pattern of enhanced CA1-mPFC theta power, synchrony, cross-frequency interaction, and neuronal coupling that strongly predicted learned resistance, and that was lacking in helpless individuals. Our findings suggest that hippocampal-prefrontal network theta activity supports cognitive mechanisms of stress coping, and its impairment may underlie vulnerability to stress-related disorders.
Two alanine aminopeptidase isoenzymes from the developing embryos of the camel tick Hyalomma dromedarii, Koch 1884 (Acari: Ixodidae)

ABSTRACT The specific activity of alanine aminopeptidase was monitored during embryonic development of the camel tick H. dromedarii and a lag period was observed during the first six days. The specific activity was increased gradually until days 15–16 and the maximum level was recorded at age 24–25 days. Two isoenzymes of alanine aminopeptidase were resolved and designated AAP1 and AAP2 and were purified from 24–25 day old eggs of H. dromedarii by chromatography on a DEAE cellulose column and gel filtration on a Sephacryl S-300 column. The purification of AAP1 and AAP2 were increased 9.8-fold and 8.75-fold over the crude extract with recovery percentages of 30.54% and 18.0%, respectively. The molecular weight of both isoenzymes was detected to be 75 ± 2 kDa and the optimum activity of both isoenzymes was found at pH 8. MgCl2 activated AAP1, while MnCl2 and CoCl2 activated AAP2, whereas Bestatin and DTT strongly inhibited AAP1 and AAP2, respectively. Two different isoelectric points were detected at pH 8.2–8.4 and 6.6–6.8 for AAP1 and AAP2, respectively. Both AAP1 and AAP2 isoenzymes did not hydrolyse the synthetic and natural substrates of endopeptidases, indicating the absence of endopeptidase activity. Although both isoenzymes are similar, the activators, inhibitors, and isoelectric point values distinguish them.
Adaptation by copy number variation increases insecticide resistance in fall armyworms

Insecticide resistance is a major main challenge in pest control, and understanding its genetic basis is a key topic in agricultural ecology. Detoxification genes are well-known genetic elements that play a key role in adaptation to xenobiotics. The adaptive evolution of detoxification genes by copy number variations has been interpreted as a cause of insecticide resistance. However, the same pattern can be generated by the adaptation to host-plant defense toxins as well. In this study, we tested in fall armyworms (Lepidoptera Spodoptera frugiperda) if adaptation by copy number variation is the cause of the increased level of insecticide resistance from two geographic populations with different levels of resistance and two strains with different host plants. Following the generation of an assembly with chromosome-sized scaffolds (N50 = 13.2Mb), we observed that these two populations show a significant allelic differentiation of copy number variations, which is not observed between strains. In particular, a locus with almost complete allelic differentiation (Fst > 0.8) includes a cluster of P450 genes, which are well-known key players in detoxification. Detoxification genes are overrepresented in the genes with copy number variations, and the observed copy number variation appears to have beneficial effects in general. From this result, we concluded that copy number variation of detoxification genes in fall armyworms plays a key role in the insecticide resistance but not in the adaptation to host-plants, suggesting that the evolution of insecticide resistance may occur independently from host-plant adaptation.
Exogenous application of salicylic acid at different plant growth stages improves physiological processes in marigold (Tagetes erecta L.).

Marigold (Tagetes erecta L.) belongs to genus Tagetes which is famous for its ornamental beauty and medicinal values. Marigold is an herbaceous annual plant with bright flowers of varying colors and sizes. China, India and Peru are leading producers of marigold in the world. In Pakistan, it is a major floricultural crop that is available in the market throughout the year. Due to its availability in various seasons, it has become a favorite bedding and container plant among the gardening community in Pakistan. Marigold is cultivated as crop to fulfill the demand of loose flowers and garlands for decoration at various ceremonies and as raw material in different industries in the country. Marigold is being used in folk medicine since ancient times. It is evident from history that this herb has been used in religious events as well as in different therapies (Khulbe, 2015). Its aromatic nature and essential oil contents make marigold more valuable for cosmetic and perfumery industry (Devika and Koilpillai, 2014). Petals of marigold contain lutein di-esters (xanthophyll) that is used for food value addition, manufacturing drugs, as natural colorant in textile dying and for manufacturing of poultry feed to get yellow egg skin and yolk naturally (Deineka et al., 2014). Its flower extract has mosquitocidal properties and can potentially be used as insecticide (Mavi, 2014). Extracts of leaves and roots of marigold have been reported to contain triterpene, thiophene, and steroids (Munhoza et al., 2014). For biological control of nematodes, marigold leaf extract is applied to nematode affected crops (Balbaa et al., 2008). Among all abiotic stresses, drought stress affects plant growth the most and it is considered the major reason of yield loss in important crops all over the world. Shortage of irrigation water, puts stress on plant growth and reduces crop yield (Ashraf, 2010). Drought causes disturbances in photosynthetic rate as stomata are closed to avoid water loss in plants (Moussa, 2006; Mastalerczuk et al., 2017) and activities of many enzymes involved in Calvin cycle (Monakhova and Chernyadev, 2002). Water deficit is major cause of reduction in plants water contents and growth which leads to crop failure (Zhang et al., 2011). As a result of these changes some allied changes, like production of various unstable molecules of oxygen produce in mitochondria and chloroplast which are known as active/reactive oxygen species (ROS) (Arora et al., 2002). When ROS are overproduced, they cause lipid peroxidation (Zhang et al., 2011) and damage chlorophyll, protein, deoxyribonucleic acid (DNA), lipids and various important organic molecules in plant cells (Jiang and Zhang, 2001). Pak. J. Agri. Sci., Vol. 56(3), 541-548; 2019 ISSN (Print) 0552-9034, ISSN (Online) 2076-0906 DOI: 10.21162/PAKJAS/19.7276 http://www.pakjas. com.pk
Short interval intracortical inhibition as measured by TMS-EEG

The diagnosis of amyotrophic lateral sclerosis (ALS) relies on involvement of both upper (UMN) lower motor neurons (LMN). Yet, there remains no objective marker of UMN involvement, limiting early diagnosis of ALS. This study establishes whether TMS combined with EEG can be used to measure short-interval intracortical inhibition (SICI) via TMS evoked potentials (TEP) in healthy volunteers - an essential first step in developing an independent marker of UMN involvement in ALS. We hypothesised that a SICI paradigm would result in characteristic changes in the TMS-evoked EEG potentials that directly mirror the changes in MEP. TMS was delivered to the left motor cortex using single-pulse and three inhibitory stimulation paradigms. SICI was present in all three conditions. TEP peaks were reduced predominantly under the SICI 70 protocol but less so for SICI 80 and not at all for SICI 90. There was a significant negative correlation between MEPs and N45 TEP peak for SICI 70 (rho = −0.54, p = 0.04). In other words, as MEPs becomes inhibited the N45 increases. The same trend was maintained across SICI 80 and 90 (SICI 80, rho = −0.5, p = 0.06; SICI 90, rho = −0.48, p = 0.07). Additional experiments suggest these results cannot be explained by artefact. We establish that motor cortical inhibition can be measured during a SICI 70 protocol expanding on previous work. We have carefully considered the role of artefact in TEPs and have taken a number of steps to show that artefact cannot explain these results and we suggesting the differences are cortical in origin. TMS-EEG has potential to aid early diagnosis and to further understand central and peripheral pathophysiology in MND.
A single-sample circadian biomarker that performs across populations and platforms

Background For circadian medicine to influence health, such as when to take a drug or undergo a procedure, a practical way to measure body time is needed. Recent machine learning algorithms show that gene expression data from blood and skin can provide reliable estimates of body time. However, for clinical viability, a biomarker must be easily measured and generalizable to a broad population. It is not clear that any circadian biomarker yet satisfies these criteria. Results We analyzed 24 h molecular rhythms in human dermis and epidermis at three distinct body sites, leveraging both longitudinal and population data. Circadian clock function was strongest in the epidermis, regardless of body site. We identified a 12-gene biomarker set that reported circadian phase to within 3 hours from a single sample of epidermis—the skin’s most superficial layer. This set performed well across body sites, ages, sexes, and detection platforms. Conclusions This research shows that the clock in epidermis is more robust than dermis regardless of body site. To encourage ongoing validation of this biomarker in diverse populations, diseases, and experimental designs, we developed SkinPhaser–a user-friendly app to test biomarker performance in datasets (https://github.com/gangwug/SkinPhaser).
Siglec‐F is induced by granulocyte–macrophage colony‐stimulating factor and enhances interleukin‐4‐induced expression of arginase‐1 in mouse macrophages

Siglecs are cell surface lectins that recognize sialic acids and are primarily expressed in hematopoietic cells. Previous studies showed that some Siglecs regulate macrophage function. In the present study, we examined the induction and putative roles of mouse Siglec‐F in bone‐marrow‐derived macrophages in mice. A quantitative RT‐PCR analysis showed that the basal expression of Siglec‐F was weak in bone‐marrow‐derived macrophages differentiated by macrophage colony‐stimulating factor. However, a 24‐hr stimulation with granulocyte–macrophage colony‐stimulating factor (GM‐CSF) enhanced Siglec‐F expression. GM‐CSF also enhanced Siglec‐F expression in thioglycollate‐induced peritoneal macrophages. The inhibition of signal transducer and activator of transcription 5 (STAT5), but not that of phosphoinositide 3‐kinase or mitogen‐activated protein kinase kinase, significantly reduced the induction of Siglec‐F. Interleukin‐3, which uses a common β‐chain shared with the GM‐CSF receptor to stimulate the STAT5 pathway, also enhanced Siglec‐F expression. The knockdown of Siglec‐F by a specific small interfering RNA enhanced GM‐CSF‐induced STAT5 phosphorylation, suggesting that Siglec‐F down‐regulates its own expression upon prolonged GM‐CSF stimulation. Furthermore, the knockdown of Siglec‐F reduced the STAT6 phosphorylation and expression of arginase‐1 in interleukin‐4‐stimulated macrophages. These results suggest that Siglec‐F fine‐tunes the immune responses of macrophages.
Origins of global mountain plant biodiversity: Testing the ‘mountain‐geobiodiversity hypothesis’

Our objective is to analyse global‐scale patterns of mountain biodiversity and the driving forces leading to the observed patterns. More specifically, we test the ‘mountain geobiodiversity hypothesis’ (MGH) which is based on the assumption that it is not mountain‐uplift alone which drives the evolution of mountain biodiversity, but rather the combination of geodiversity evolution and Neogene and Pleistocene climate changes. We address the following questions: (a) Do areas of high geodiversity and high biodiversity in mountains overlap, that is can mountain geodiversity predict mountain biodiversity? (b) What is the role of Pleistocene climate change in shaping mountain biodiversity? (c) Did diversification rate shifts occur predominantly with the onset of more pronounced climate fluctuations in the late Neogene and Pleistocene fostering a ‘species pump’ effect, as predicted by the MGH?
Sesenta y cuatro nuevos registros para la flora del Perú a través de inventarios biológicos rápidos en la Amazonía peruana

Durante el período 2000 – 2016, se llevaron a cabo 15 inventarios biológicos en áreas remotas en el pie de monte andino y el llano amazónico del Perú. En estos inventarios, 27 botánicos colectaron un total de 9397 especímenes de plantas vasculares fértiles. Hasta finales del 2017, más de la mitad de estos especímenes se han identificado a nivel de especie, de los cuales 64 especies y 2 géneros (Dicorynia y Monopteryx) representan nuevos registros para la flora del Perú. Si esta tasa de novedades se mantiene, el número de registros nuevos en el material de los inventarios podría aumentar, lo cual nos indica que aún queda mucho por descubrir en la flora andino-amazónica del Perú.