Follicle development as an orchestrated signaling network in a 3D organoid

Abstract The ovarian follicle is the structural and functional unit of the ovary, composed of the female gamete (the oocyte) and supportive somatic cells. Follicles are not only the source of a female’s germ cell supply, but also secrete important hormones necessary for proper endocrine function. Folliculogenesis, the growth and maturation of the follicular unit, is a complex process governed by both intrafollicular crosstalk and pituitary-secreted hormones. While the later stages of this process are gonadotropin-dependent, early folliculogenesis appears to be controlled by the ovarian microenvironment and intrafollicular paracrine and autocrine signaling. In vitro follicle culture remains challenging because of the limited knowledge of growth factors and other cytokines influencing early follicle growth. Here we discuss the current state of knowledge on paracrine and autocrine signaling influencing primary follicles as they develop into the antral stage. Given the importance of intrafollicular signaling and the ovarian microenvironment, we reviewed the current engineering approaches for in vitro follicle culture, including 3D systems using natural hydrogels such as alginate and synthetic hydrogels such as poly(ethylene glycol). Our discussion is focused on what drives the proliferation of granulosa cells, development of the thecal layer, and antrum formation—three processes integral to follicle growth up to the antral stage. Further research in this area may reveal the mechanisms behind these complex signaling relationships within the follicle, leading to more successful and physiologically-relevant in vitro culture methods that will translate well to clinical applications.https://deepblue.lib.umich.edu/bitstream/2027.42/146779/1/13036_2018_Article_134.pd

First screening of bacterial communities of Microdon myrmicae and its ant host: do microbes facilitate the invasion of ant colonies by social parasites?

Abstract Many studies have highlighted how numerous bacteria provide their hosts essential nutrients or protection against pathogens, parasites and predators. Nevertheless, the role of symbiotic microorganisms in the interactions between social insects and their parasites is still poorly known. Microdon (Diptera, Syrphidae) is a peculiar fly genus whose larvae are able to successfully infiltrate ant colonies and feed upon the ant brood. Using high throughput 16S rRNA gene amplicon sequencing, we provide the first microbiome survey of Mi. myrmicae larvae and larvae and workers of its host, Myrmica scabrinodis, collected from two sites in England. We analyzed the microbiome of the external surface of the cuticle and the internal microbiome of the body separately. The results clearly show that the Mi. myrmicae microbiome significantly differs from that of its host, while no substantial dissimilarity was detected across the microbiome of ant workers and ant larvae. Microdon myrmicae microbiome varies across the two analyzed sites suggesting that bacteria communities of Mi. myrmicae are derived from the environment rather than by horizontal transmission between hosts and parasites. Families Streptococcaceae, Carnobacteriaceae and Rizhobiaceae are dominant in My. scabrinodis, and Spiroplasma is dominant in ant workers. Microbiome of Mi. myrmicae larvae is mainly characterized by the family Anaplasmataceae, with Wolbachia as predominant genus. Interestingly, we found Serratia within both Mi. myrmicae and Myrmica larvae. Bacteria of this genus are known to produce a family of pyrazines commonly involved in ant communication, which could play a role in Microdon/ant interaction

J-Band Infrared Spectroscopy of a Sample of Brown Dwarfs Using Nirspec on Keck II

Near-infrared spectroscopic observations of a sample of very cool, low-mass objects are presented with higher spectral resolution than in any previous studies. Six of the objects are L-dwarfs, ranging in spectral class from L2 to L8/9, and the seventh is a methane or T-dwarf. These new observations were obtained during commissioning of NIRSPEC, the first high-resolution near-infrared cryogenic spectrograph for the Keck II 10-meter telescope on Mauna Kea, Hawaii. Spectra with a resolving power of R=2500 from 1.135 to 1.360 microns (approximately J-band) are presented for each source. At this resolution, a rich spectral structure is revealed, much of which is due to blending of unresolved molecular transitions. Strong lines due to neutral potassium (K I), and bands due to iron hydride (FeH) and steam (H2O) change significantly throughout the L sequence. Iron hydride disappears between L5 and L8, the steam bands deepen and the K I lines gradually become weaker but wider due to pressure broadening. An unidentified feature occurs at 1.22 microns which has a temperature dependence like FeH but has no counterpart in the available FeH opacity data. Because these objects are 3-6 magnitudes brighter in the near-infrared compared to the I-band, spectral classification is efficient. One of the objects studied (2MASSW J1523+3014) is the coolest L-dwarf discovered so far by the 2-Micron All-Sky Survey (2MASS), but its spectrum is still significantly different from the methane-dominated objects such as Gl229B or SDSS 1624+0029.Comment: New paper, Latex format, 2 figures, accepted to ApJ Letter

Magnetohydrodynamics of Cloud Collisions in a Multi-phase Interstellar Medium

We extend previous studies of the physics of interstellar cloud collisions by beginning investigation of the role of magnetic fields through 2D magnetohydrodynamic (MHD) numerical simulations. We study head-on collisions between equal mass, mildly supersonic diffuse clouds. We include a moderate magnetic field and two limiting field geometries, with the field lines parallel (aligned) and perpendicular (transverse) to the colliding cloud motion. We explore both adiabatic and radiative cases, as well as symmetric and asymmetric ones. We also compute collisions between clouds evolved through prior motion in the intercloud medium and compare with unevolved cases. We find that: In the (i) aligned case, adiabatic collisions, like their HD counterparts, are very disruptive, independent of the cloud symmetry. However, when radiative processes are taken into account, partial coalescence takes place even in the asymmetric case, unlike the HD calculations. In the (ii) transverse case, collisions between initially adjacent unevolved clouds are almost unaffected by magnetic fields. However, the interaction with the magnetized intercloud gas during the pre-collision evolution produces a region of very high magnetic energy in front of the cloud. In collisions between evolved clouds with transverse field geometry, this region acts like a ``bumper'', preventing direct contact between the clouds, and eventually reverses their motion. The ``elasticity'', defined as the ratio of the final to the initial kinetic energy of each cloud, is about 0.5-0.6 in the cases we considered. This behavior is found both in adiabatic and radiative cases.Comment: 40 pages in AAS LaTeX v4.0, 13 figures (in degraded jpeg format). Full resolution images as well as mpeg animations are available at http://www.msi.umn.edu:80/Projects/twj/mhd-cc/ . Accepted for publication in The Astrophysical Journa

Acylpeptide hydrolase: inhibitors and some active site residues of the human enzyme.

Acylpeptide hydrolase may be involved in N-terminal deacetylation of nascent polypeptide chains and of bioactive peptides. The activity of this enzyme from human erythrocytes is sensitive to anions such as chloride, nitrate, and fluoride. Furthermore, blocked amino acids act as competitive inhibitors of the enzyme. Acetyl leucine chloromethyl ketone has been employed to identify one active site residue as His-707. Diisopropylfluorophosphate has been used to identify a second active site residue as Ser-587. Chemical modification studies with a water-soluble carbodiimide implicate a carboxyl group in catalytic activity. These results and the sequence around these active site residues, especially near Ser-587, suggest that acylpeptide hydrolase contains a catalytic triad. The presence of a cysteine residue in the vicinity of the active site is suggested by the inactivation of the enzyme by sulfhydryl-modifying agents and also by a low amount of modification by the peptide chloromethyl ketone inhibitor. Ebelactone A, an inhibitor of the formyl aminopeptidase, the bacterial counterpart of eukaryotic acylpeptide hydrolase, was found to be an effective inhibitor of this enzyme. These findings suggest that acylpeptidase hydrolase is a member of a family of enzymes with extremely diverse functions

Torus knots and mirror symmetry

We propose a spectral curve describing torus knots and links in the B-model. In particular, the application of the topological recursion to this curve generates all their colored HOMFLY invariants. The curve is obtained by exploiting the full Sl(2, Z) symmetry of the spectral curve of the resolved conifold, and should be regarded as the mirror of the topological D-brane associated to torus knots in the large N Gopakumar-Vafa duality. Moreover, we derive the curve as the large N limit of the matrix model computing torus knot invariants.Comment: 30 pages + appendix, 3 figure

Critical temperature of non-interacting Bose gases on disordered lattices

For a non-interacting Bose gas on a lattice we compute the shift of the critical temperature for condensation when random-bond and onsite disorder are present. We evidence that the shift depends on the space dimensionality D and the filling fraction f. For D -> infinity (infinite-range model), using results from the theory of random matrices, we show that the shift of the critical temperature is negative, depends on f, and vanishes only for large f. The connections with analogous results obtained for the spherical model are discussed. For D=3 we find that, for large f, the critical temperature Tc is enhanced by disorder and that the relative shift does not sensibly depend on f; at variance, for small f, Tc decreases in agreement with the results obtained for a Bose gas in the continuum. We also provide numerical estimates for the shift of the critical temperature due to disorder induced on a non-interacting Bose gas by a bichromatic incommensurate potential.Comment: 18 pages, 8 figures; Fig. 8 improved adding results for another value of q (q=830/1076

Development and validation of a new MRI simulation technique that can reliably estimate optimal in vivo scanning parameters in a glioblastoma murine model

BACKGROUND: Magnetic Resonance Imaging (MRI) relies on optimal scanning parameters to achieve maximal signal-to-noise ratio (SNR) and high contrast-to-noise ratio (CNR) between tissues resulting in high quality images. The optimization of such parameters is often laborious, time consuming, and user-dependent, making harmonization of imaging parameters a difficult task. In this report, we aim to develop and validate a computer simulation technique that can reliably provide optimal in vivo scanning parameters ready to be used for in vivo evaluation of disease models. METHODS: A glioblastoma murine model was investigated using several MRI imaging methods. Such MRI methods underwent a simulated and an in vivo scanning parameter optimization in pre- and post-contrast conditions that involved the investigation of tumor, brain parenchyma and cerebrospinal fluid (CSF) CNR values in addition to the time relaxation values of the related tissues. The CNR tissues information were analyzed and the derived scanning parameters compared in order to validate the simulated methodology as a reliable technique for optimal in vivo scanning parameters estimation. RESULTS: The CNRs and the related scanning parameters were better correlated when spin-echo-based sequences were used rather than the gradient-echo-based sequences due to augmented inhomogeneity artifacts affecting the latter methods. Optimal in vivo scanning parameters were generated successfully by the simulations after initial scanning parameter adjustments that conformed to some of the parameters derived from the in vivo experiment. CONCLUSION: Scanning parameter optimization using the computer simulation was shown to be a valid surrogate to the in vivo approach in a glioblastoma murine model yielding in a better delineation and differentiation of the tumor from the contralateral hemisphere. In addition to drastically reducing the time invested in choosing optimal scanning parameters when compared to an in vivo approach, this simulation program could also be used to harmonize MRI acquisition parameters across scanners from different vendors

NLL+NNLO predictions for jet-veto efficiencies in Higgs-boson and Drell-Yan production

Using the technology of the CAESAR approach to resummation, we examine the jet-veto efficiency in Higgs-boson and Drell-Yan production at hadron colliders and show that at next-to-leading logarithmic (NLL) accuracy the resummation reduces to just a Sudakov form factor. Matching with NNLO calculations results in stable predictions for the case of Drell-Yan production, but reveals substantial uncertainties in gluon-fusion Higgs production, connected in part with the poor behaviour of the perturbative series for the total cross section. We compare our results to those from POWHEG with and without reweighting by HqT, as used experimentally, and observe acceptable agreement. In an appendix we derive the part of the NNLL resummation corrections associated with the radius dependence of the jet algorithm.Comment: 30 pages, 8 figures; v2 as published in JHE

FTO and MC4R Gene Variants Are Associated with Obesity in Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility in women. It is also associated with metabolic disturbances that place women at increased risk for obesity and type 2 diabetes. There is strong evidence for familial clustering of PCOS and a genetic predisposition. However, the gene(s) responsible for the PCOS phenotypes have not been elucidated. This two-phase family-based and case-control genetic study was designed to address the question of whether SNPs identified as susceptibility loci for obesity in genome-wide association studies (GWAS) are also associated with PCOS and elevated BMI. Members of 439 families having at least one offspring with PCOS were genotyped for 15 SNPs previously shown to be associated with obesity. Linkage and association with PCOS was assessed using the transmission/disequilibrium test (TDT). These SNPs were also analyzed in an independent case-control study involving 395 women with PCOS and 176 healthy women with regular menstrual cycles. Only one of these 15 SNPs (rs2815752 in NEGR1) was found to have a nominally significant association with PCOS (χ2 = 6.11, P = 0.013), but this association failed to replicate in the case-control study. While not associated with PCOS itself, five SNPs in FTO and two in MC4R were associated with BMI as assessed with a quantitative-TDT analysis, several of which replicated association with BMI in the case-control cohort. These findings demonstrate that certain SNPs associated with obesity contribute to elevated BMI in PCOS, but do not appear to play a major role in PCOS per se. These findings support the notion that PCOS phenotypes are a consequence of an oligogenic/polygenic mechanism