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Gut microbiota in non-obese adolescent girls with polycystic ovary syndrome: effects of randomized treatments
<p class="Paragraph"><span><span><span><span><span><span><span><span><span><span><span><b>Context:</b> Women and obese adolescent girls with polycystic ovary syndrome (PCOS) have altered gut microbiota. </span></span></span></span></span></span></span></span></span></span></span></p> <p class="Paragraph"><span><span><span><span><span><span><span><span><span><span><span><b>Objective:</b> To study the gut microbiota composition of non-obese adolescent girls with PCOS and the effects of randomized pharmacological treatments.</span></span></span></span></span></span></span></span></span></span></span></p> <p class="Paragraph"><span><span><span><span><span><span><span><span><span><span><span><b>Design:</b> Randomized, open-label, single-center controlled trial. </span></span></span></span></span></span></span></span></span></span></span></p> <p class="Paragraph"><span><span><span><span><span><span><span><span><span><span><span><b>Settings:</b> Endocrinology Department, University Hospital. </span></span></span></span></span></span></span></span></span></span></span></p> <p class="Paragraph"><span><span><span><span><span><span><span><span><span><span><span><b>Participants: </b>30 girls with PCOS [age 15.8 years; body mass index (BMI) 25 kg/ m<sup>2</sup>] and 31 controls [age 15.9 years; BMI 22 kg/ m<sup>2</sup>]. </span></span></span></span></span></span></span></span></span></span></span></p> <p class="Paragraph"><span><span><span><span><span><span><span><span><span><span><span><b>Intervention:</b> PCOS girls were randomized to receive an oral contraceptive (OC, N= 15) or spironolactone-pioglitazone-metformin (SPIOMET, N= 15) for 1 year. </span></span></span></span></span></span></span></span></span></span></span></p> <p class="Paragraph"><span><span><span><span><span><span><span><span><span><span><span><b>Outcomes: </b>16S ribosomal subunit gene amplicon sequencing was used to describe and quantify microbial diversity and taxonomic profiles in stool samples from all subjects. Samples from 23 out of 30 girls with PCOS (OC, N= 11; SPIOMET, N= 12) were available for analysis post-treatment. Correlations between bacterial results and endocrine-metabolic variables were performed before and after randomized treatments. </span></span></span></span></span></span></span></span></span></span></span></p> <p class="Paragraph"><span><span><span><span><span><span><span><span><span><span><span><b>Results:</b> Girls with PCOS had decreased diversity alpha, altered microbiota pattern and taxonomic profile with more abundance of <i>Family XI</i> (<i>P</i>= 0.002), and less abundance of family <i>Prevotellaceae</i> (<i>P</i>= 0.0006) and the genus <i>Prevotella</i> (<i>P</i>= 0.0001) and <i>Senegalimassilia</i> (<i>P</i>< 0.0001), as compared to controls. <i>Family XI</i>abundance related positively to hepato-visceral fat (R= 0.453; <i>P</i>= 0.0003). SPIOMET treatment, but not OC, normalized the abundance of <i>Family XI</i>. <i>Prevotellaceae</i>, <i>Prevotella</i> and <i>Senegalimassilia</i> abundance remained unchanged after either treatment. </span></span></span></span></span></span></span></span></span></span></span></p> <p class="Paragraph"><span><span><span><span><span><span><span><span><span><span><span><b>Conclusion:</b> SPIOMET's spectrum of normalizing effects in non-obese girls with PCOS is herewith broadened as to include <i>Family XI</i> abundance in gut microbiota. </span></span></span></span></span></span></span></span></span></span></span></p>
Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome
<p><span>The effects of how obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring are unclear. We found that daughters of PCOS mothers are more likely to be diagnosed with PCOS in a Swedish nationwide register-based cohort and a clinical case-control study from Chile. Further, female mice (F0) with PCOS-like traits induced by late gestation injection of dihydrotestosterone, with and without obesity, produced female F1–F3 offspring with a PCOS-like reproductive and metabolic phenotypes. Sequencing of single MII oocytes from F1–F3 offspring revealed common and unique altered gene expression across all generations. Notably, four genes were also differentially expressed in serum samples from daughters in the case-control study and unrelated women with PCOS. Our findings provide evidence of transgenerational effects in female offspring of PCOS mothers and identify possible candidate genes for the prediction of a PCOS phenotype in future generations.</span></p>
Characterization and mutagenesis of Chinese hamster ovary cells endogenous retroviruses to inactivate viral particle release
<p>The Chinese hamster ovary (CHO) cells used to produce biopharmaceutical proteins are known to contain type‐C endogenous retrovirus (ERV) sequences in their genome and to release retroviral‐like particles. Although evidence for their infectivity is missing, this has raised safety concerns. As the genomic origin of these particles remained unclear, we characterized type‐C ERV elements at the genome, transcriptome, and viral particle RNA levels. We identified 173 type‐C ERV sequences clustering into three functionally conserved groups. Transcripts from one type‐C ERV group were full‐ length, with intact open reading frames, and cognate viral genome RNA was loaded into retroviral‐like particles, suggesting that this ERV group may produce functional viruses. CRISPR‐Cas9 genome editing was used to disrupt the gag gene of the expressed type‐C ERV group. Comparison of CRISPR‐derived mutations at the DNA and RNA level led to the identification of a single ERV as the main source of the release of RNA‐loaded viral particles. Clones bearing a Gag loss‐of‐function mutation in this ERV showed a reduction of RNA‐containing viral particle release down to detection limits, without compromising cell growth or therapeutic protein production. Overall, our study provides a strategy to mitigate potential viral particle contaminations resulting from ERVs during biopharmaceutical manufacturing.</p>
DOES OBESITY DRIVE THE DEVELOPMENT OF POLYCYSTIC OVARY SYNDROME? AN EPIDEMIOLOGIC STUDY (SUPPLEMENTARY TABLES)
<p>These are the Supplementary tables for manuscript entitled 'Does Obesity Drive the Development of Polycystic Ovary Syndrome? An Epidemiologic Study', denoting: Table 1: the search strategy for the systematic review; Table 2: the NOS quality scoring of included studies; and Table 3: the association between mean BMI or obesity prevalence and PCOS prevalence by PCOS diagnostic criteria. </p>
Characterisation of large transgene integrations in Chinese hamster ovary cells using a bioengineered mammalian transposase
<p>Supporting information for "Characterisation of large transgene integrations in Chinese hamster ovary cells using a bioengineered mammalian transposase"</p>
FIGURE 2. Bulbophyllum versicolor. A. Column with ovary. B. Lip. C. Dorsal sepal. D. Petal. E. Anther cap and pollinarium. F. Lateral sepal. G in Bulbophyllum versicolor (Orchidaceae, Malaxideae), a new species from Yunnan, China: evidence from morphology and molecular analyses
FIGURE 2. Bulbophyllum versicolor. A. Column with ovary. B. Lip. C. Dorsal sepal. D. Petal. E. Anther cap and pollinarium. F. Lateral sepal. G. Plant.
Effect of acupuncture and metformin on insulin sensitivity in women with polycystic ovary syndrome and insulin resistance: a three-armed randomized controlled trial
<p>STUDY QUESTION</p> <p>Does acupuncture improve insulin sensitivity more effectively than metformin or sham acupuncture in women with polycystic ovary syndrome (PCOS) and insulin resistance (IR)?</p> <p>SUMMARY ANSWER</p> <p>Among women with PCOS and IR, acupuncture was not more effective than metformin or sham acupuncture in improving insulin sensitivity.</p> <p>WHAT IS KNOWN ALREADY</p> <p>Uncontrolled trials have shown that acupuncture improved insulin sensitivity with fewer side effects compared with metformin in women with PCOS and IR. However, data from randomized trials between acupuncture and metformin or sham acupuncture are lacking.</p> <p>STUDY DESIGN, SIZE, DURATION</p> <p>This was a three-armed randomized controlled trial enrolling a total of 342 women with PCOS and IR from three hospitals between November 2015 and February 2018, with a 3-month follow-up until October 2018.</p> <p>PARTICIPANTS/MATERIALS, SETTING, METHODS</p> <p>Women aged from 18 to 40 years with PCOS and homeostasis model assessment of insulin resistance (HOMA-IR) ≥2.14 were randomly assigned (n = 114 per group) to receive true acupuncture plus placebo (true acupuncture), metformin plus sham acupuncture (metformin, 0.5 g three times daily) or sham acupuncture plus placebo (sham acupuncture) for 4 months, with an additional 3-month follow-up. True or sham acupuncture was given three times per week, and 0.5 g metformin or placebo was given three times daily. The primary outcome was change in HOMA-IR from baseline to 4 months after baseline visit. Secondary outcomes included changes in the glucose AUC during an oral glucose tolerance test, BMI and side effects at 4 months after baseline visit.</p> <p>MAIN RESULTS AND THE ROLE OF CHANCE</p> <p>After 4 months of treatment, the changes of HOMA-IR were –0.5 (decreased 14.7%) in the true acupuncture group, –1.0 (decreased 25.0%) in the metformin group and –0.3 (decreased 8.6%) in the sham acupuncture group, when compared with baseline. True acupuncture is not as effective as metformin in improving HOMA-IR at 4 months after baseline visit (difference, 0.6; 95% CI, 0.1–1.1). No significant difference was found in change in HOMA-IR between true and sham acupuncture groups at 4 months after baseline visit (difference, –0.2; 95% CI, –0.7 to 0.3). During the 4 months of treatment, gastrointestinal side effects were more frequent in the metformin group, including diarrhea, nausea, loss of appetite, fatigue, vomiting and stomach discomfort (31.6%, 13.2%, 11.4%, 8.8%, 14.0% and 8.8%, respectively). Bruising was more common in the true acupuncture group (14.9%).</p> <p>LIMITATIONS, REASONS FOR CAUTION</p> <p>This study might have underestimated the sample size in the true acupuncture group with 4 months of treatment to enable detection of statistically significant changes in HOMA-IR with fixed acupuncture (i.e. a non-personalized protocol). Participants who withdrew because of pregnancy did not have further blood tests and this can introduce bias.</p> <p>WIDER IMPLICATIONS OF THE FINDINGS</p> <p>True acupuncture did not improve insulin sensitivity as effectively as metformin in women with PCOS and IR, but it is better than metformin in improving glucose metabolism (which might reduce the risk of type 2 diabetes) and has less side effects. Metformin had a higher incidence of gastrointestinal adverse effects than acupuncture groups, and thus acupuncture might be a non-pharmacological treatment with low risk for women with PCOS. Further studies are needed to evaluate the effect of acupuncture combined with metformin on insulin sensitivity in these women.</p> <p>STUDY FUNDING/COMPETING INTEREST(S)</p> <p>This work was supported by grants 2017A020213004 and 2014A020221060 from the Science and Technology Planning Project of Guangdong Province. The authors have no conflicts of interest.</p> <p>TRIAL REGISTRATION NUMBER</p> <p>Clinicaltrials.gov number: NCT02491333.</p> <p>TRIAL REGISTRATION DATE</p> <p>8 July 2015.</p> <p>DATE OF FIRST PATIENT'S ENROLLMENT</p> <p>11 November 2015.</p>
FIGURE. Images of representative members of tribe Phyllantheae. (A) Flowers of Nellica maderaspatensis. (B) Pistillate flowers of Cathetus gracilis, note the unique disc covering the ovary. (C) Pistillate and staminate flowers of Cathetus glaucophyllus. (D) Staminate flowers of Nymphanthus glaucescens. (E) Fruits of Kirganelia muelleriana. (F) Fruits of Lysiandra subcrenulata. (G) Phylloclade with flowers of Phyllanthus angustifolius. (H) Flowering branchlet of Phyllanthus incrustatus, note the ornamentation on the axes. (I) Habit of Moeroris tenella. (J) Fruiting branch of Dendrophyllanthus tenuirhachis. (K) Fruits of Cicca profusa. (L) Fruiting branch of Emblica officinalis. (M) Flowering plant of Emblica urinaria. (N) Pistillate flower of Breynia disticha. (O) Staminate flower of Breynia disticha. (P) flower of Glochidion dunnianum. (Q) Staminate of Glochidion lanceolarium. (R) Dehisced capsule of Glochidion sp. showing seeds covered with a red sarcotesta. Photos: A & F by J.J. Bruhl; B & P by M.S. Nuraliev; C by T. Williams; E & K by C. Jongkind; H by B. Falcón; J by R.-Y. Yu; D, G, I, L, M, N, O, Q & R by R.W.Bouman. in A revised phylogenetic classification of tribe Phyllantheae (Phyllanthaceae)
FIGURE. Images of representative members of tribe Phyllantheae. (A) Flowers of Nellica maderaspatensis. (B) Pistillate flowers of Cathetus gracilis, note the unique disc covering the ovary. (C) Pistillate and staminate flowers of Cathetus glaucophyllus. (D) Staminate flowers of Nymphanthus glaucescens. (E) Fruits of Kirganelia muelleriana. (F) Fruits of Lysiandra subcrenulata. (G) Phylloclade with flowers of Phyllanthus angustifolius. (H) Flowering branchlet of Phyllanthus incrustatus, note the ornamentation on the axes. (I) Habit of Moeroris tenella. (J) Fruiting branch of Dendrophyllanthus tenuirhachis. (K) Fruits of Cicca profusa. (L) Fruiting branch of Emblica officinalis. (M) Flowering plant of Emblica urinaria. (N) Pistillate flower of Breynia disticha. (O) Staminate flower of Breynia disticha. (P) flower of Glochidion dunnianum. (Q) Staminate of Glochidion lanceolarium. (R) Dehisced capsule of Glochidion sp. showing seeds covered with a red sarcotesta. Photos: A & F by J.J. Bruhl; B & P by M.S. Nuraliev; C by T. Williams; E & K by C. Jongkind; H by B. Falcón; J by R.-Y. Yu; D, G, I, L, M, N, O, Q & R by R.W.Bouman.
FIGURE. Scanning electron micrographs of the disc ovaries/cypselae in Callilepis taxa with imbricate involucral bracts.A. Disc cypsela of C. caerulea showing glabrous surface and twin hairy ciliate margins and B. higher magnification showing the twin hairs along the margin in C. caerulea (Hemm 404, PRE). C. Disc ovary of C. corymbosa showing glabrous surface and twin hairy ciliate margins and D. higher magnification showing the twin hairs along the margin in C. corymbosa (Koekemoer 2596, PRE). in A taxonomic revision of the genus Callilepis (Asteraceae) in South Africa
FIGURE. Scanning electron micrographs of the disc ovaries/cypselae in Callilepis taxa with imbricate involucral bracts.A. Disc cypsela of C. caerulea showing glabrous surface and twin hairy ciliate margins and B. higher magnification showing the twin hairs along the margin in C. caerulea (Hemm 404, PRE). C. Disc ovary of C. corymbosa showing glabrous surface and twin hairy ciliate margins and D. higher magnification showing the twin hairs along the margin in C. corymbosa (Koekemoer 2596, PRE).
FIGURE. Disc ovary in a taxon of Callilepis with imbricate involucral bracts. A. Digital image of the disc ovary of C. normae (Koekemoer 4573, PRE) showing the entire surface twin hairy. B. Scanning electron micrograph of the surface of the disc ovary of C. normae (Koekemoer 4573, PRE) showing the twin hairs on the surface. in A taxonomic revision of the genus Callilepis (Asteraceae) in South Africa
FIGURE. Disc ovary in a taxon of Callilepis with imbricate involucral bracts. A. Digital image of the disc ovary of C. normae (Koekemoer 4573, PRE) showing the entire surface twin hairy. B. Scanning electron micrograph of the surface of the disc ovary of C. normae (Koekemoer 4573, PRE) showing the twin hairs on the surface.
FIGURE. Disc cypselae and pappus in Callilepis taxa. A. Scanning electron micrograph of the laterally compressed disc cypsela of C. laureola var. laureola with one long and one short awn (Bester 13813, PRE). B. Digital image of the inner ray floret of C. leptophylla with laterally compressed ovary, one long awn and one short awn (Van Vuuren 1307, PRE). C. and D. Scanning electron micrographs of the disc cypselae of C. lancifolia: C, with one pappus awn and scales and D, no pappus awns, only scales (Koekemoer 5555, PRE). in A taxonomic revision of the genus Callilepis (Asteraceae) in South Africa
FIGURE. Disc cypselae and pappus in Callilepis taxa. A. Scanning electron micrograph of the laterally compressed disc cypsela of C. laureola var. laureola with one long and one short awn (Bester 13813, PRE). B. Digital image of the inner ray floret of C. leptophylla with laterally compressed ovary, one long awn and one short awn (Van Vuuren 1307, PRE). C. and D. Scanning electron micrographs of the disc cypselae of C. lancifolia: C, with one pappus awn and scales and D, no pappus awns, only scales (Koekemoer 5555, PRE).
FIGURE. The receptacle and paleae in the genus Callilepis. A. Digital image of the conical receptacle in the solitary capitulum of C. lancifolia (Galpin 12433, PRE). B. Digital image of the conical receptacle in the capitulum from the corymbose synflorescence in C. normae (Theron 3568, PRE). C. Digital image of the palea clasping the disc ovary of C. leptophylla (Hobson 1970, PRE). D. Digital image of the palea enveloping the disc ovary of C normae (Koekemoer 4573, PRE). Arrows in C and D indicate the centre of the capitulum. in A taxonomic revision of the genus Callilepis (Asteraceae) in South Africa
FIGURE. The receptacle and paleae in the genus Callilepis. A. Digital image of the conical receptacle in the solitary capitulum of C. lancifolia (Galpin 12433, PRE). B. Digital image of the conical receptacle in the capitulum from the corymbose synflorescence in C. normae (Theron 3568, PRE). C. Digital image of the palea clasping the disc ovary of C. leptophylla (Hobson 1970, PRE). D. Digital image of the palea enveloping the disc ovary of C normae (Koekemoer 4573, PRE). Arrows in C and D indicate the centre of the capitulum.
FIGURE. Aristolochia rethyae—A. Flower in pre-anthesis; B. Frontal view of flower; C. Lateral view of flower; D. Longitudinal section of utricle showing the gynostemium; E. Tip of the gynostemium; F. Stamens on gynostemium; G. Cross section of gynostemium showing the stamen arrangement; H. Cross section of ovary; I. Hair on capsule. A–C photographed by Soyala Kashung; D–I photographed by Rimi Barman. in Aristolochia rethyae, a new species from Arunachal Pradesh, north-east India
FIGURE. Aristolochia rethyae—A. Flower in pre-anthesis; B. Frontal view of flower; C. Lateral view of flower; D. Longitudinal section of utricle showing the gynostemium; E. Tip of the gynostemium; F. Stamens on gynostemium; G. Cross section of gynostemium showing the stamen arrangement; H. Cross section of ovary; I. Hair on capsule. A–C photographed by Soyala Kashung; D–I photographed by Rimi Barman.
FIGURE 11 in A Comparative Study Of The Ovaries In Some Brazilian Bees (Hymenoptera; Apoidea) G F M J E S Abstract
FIGURE 11. Relationship between the ovariole size and intertegular distance of bees (Linear regression). Data on Meliponini and Apini were excluded. Numbers regards to number of the species listed in the Table 1.
FIGURE 8 in A Comparative Study Of The Ovaries In Some Brazilian Bees (Hymenoptera; Apoidea) G F M J E S Abstract
FIGURE 8: Oocyte-nurse cell complex in the posterior region of the germarium of Melipona bicolor. Notice the presence of accessory nuclei (a) into the oocyte cytoplasm. The nurse cells present a linear arrangement and they are connected with the oocyte; tp: tunica propria; (o): oocyte; (on): oocyte nucleus; (N): nurse cell; (n): nurse cell nucleus. Bar = 10 µm.
FIGURE 5 in A Comparative Study Of The Ovaries In Some Brazilian Bees (Hymenoptera; Apoidea) G F M J E S Abstract
FIGURE 5. Longitudinal section of mature oocyte of Pseudaugochlora graminea with accessory nuclei placed in the peripheral oocyte region. The follicular cells are flattened; E: follicular epithelium; a: accessory nucleus; en: follicular epithelial cell nucleus. Bar = 10 µm.
FIGURE 3 in A Comparative Study Of The Ovaries In Some Brazilian Bees (Hymenoptera; Apoidea) G F M J E S Abstract
FIGURE 3. Longitudinal section of a follicle of Epicharis affinis, observed under phase contrast microscope, Methyl Green-Pyronin stained, showing one vitellogenic growing oocyte (o) that have the nucleus (on) and the accessory nuclei (a) placed in the peripheral region of the cytoplasm; E: follicular epithelium covering the oocyte chamber; e: follicular layer of the nutritive chamber; m: muscle; N: nurse cells; pm: peritoneal membrane; T: trachea; tp: tunica propria. Bar = 10 µm.
FIGURE 7 in A Comparative Study Of The Ovaries In Some Brazilian Bees (Hymenoptera; Apoidea) G F M J E S Abstract
FIGURE 7. Longitudinal section of the ovariole of Epicharis affinis obeserved under phase contrast microscope, Bromophenol Blue stained, showing the follicular epithelium (E) of two successive follicles with different developmental stages. Covering the mature oocyte, the follicular projection (p) that penetrate the corion (c). Notice that the epithelium cover the vitellogenic growing oocyte (o) without projections and with cells presenting different staining tonalities (*); en: follicular epithelial cell nucleus; (tp) tunica propria; (pm) peritoneal membrane; en: follicular epithelial cell nucleus. Bar = 10 µm.
FIGURE 12 in A Comparative Study Of The Ovaries In Some Brazilian Bees (Hymenoptera; Apoidea) G F M J E S Abstract
FIGURE 12. Relationship between the oocyte size and intertegular distance of bees (Linear regression). Numbers regards to number of the species listed in the Table 1
FIGURE 1 in A Comparative Study Of The Ovaries In Some Brazilian Bees (Hymenoptera; Apoidea) G F M J E S Abstract
FIGURE 1. Longitudinal section of the germarium position of Melipona quadrifasciata. The anterior region have undifferentiated cells and the posterior region have many oocyte-nurse cell complexes; o: young oocyte; on: oocyte nucleus; uc: undifferentiated cells; pm: peritoneal membrane; T: trachea; tp: tunica propria. Bar = 10 µm.
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