Models of in vitro spermatogenesis

Understanding the mechanisms that lead to the differentiation of male germ cells from their spermatogonial stem cells through meiosis to give rise to mature haploid spermatozoa has been a major quest for many decades. Unlike most other cell types this differentiation process is more or less completely dependent upon the cells being located within the strongly structured niche provided by mature Sertoli cells within an intact seminiferous epithelium. While much new information is currently being obtained through the application and description of relevant gene mutations, there is still a considerable need for in vitro models with which to explore the mechanisms involved. Not only are systems of in vitro spermatogenesis important for understanding the basic science, they have marked pragmatic value in offering ex vivo systems for the artificial maturation of immature germ cells from male infertility patients, as well as providing opportunities for the transgenic manipulation of male germ cells. In this review, we have summarized literature relating to simplistic culturing of germ cells, co-cultures of germ cells with other cell types, especially with Sertoli cells, cultures of seminiferous tubule fragments, and briefly mention the opportunities of xenografting larger testicular pieces. The majority of methods are successful in allowing the differentiation of small steps in the progress of spermatogonia to spermatozoa; few tolerate the chromosomal reduction division through meiosis, and even fewer seem able to complete the complex morphogenesis which results in freely swimming spermatozoa. However, recent progress with complex culture environments, such as 3-d matrices, suggest that possibly success is now not too far away

Universal time-dependent deformations of Schrodinger geometry

We investigate universal time-dependent exact deformations of Schrodinger geometry. We present 1) scale invariant but non-conformal deformation, 2) non-conformal but scale invariant deformation, and 3) both scale and conformal invariant deformation. All these solutions are universal in the sense that we could embed them in any supergravity constructions of the Schrodinger invariant geometry. We give a field theory interpretation of our time-dependent solutions. In particular, we argue that any time-dependent chemical potential can be treated exactly in our gravity dual approach.Comment: 24 pages, v2: references adde

A Longitudinal Cline Characterizes the Genetic Structure of Human Populations in the Tibetan Plateau

Indigenous populations of the Tibetan plateau have attracted much attention for their good performance at extreme high altitude. Most genetic studies of Tibetan adaptations have used genetic variation data at the genome scale, while genetic inferences about their de- mography and population structure are largely based on uniparental markers. To provide genome-wide information on population structure, we analyzed new and published data of 338 individuals from indigenous populations across the plateau in conjunction with world- wide genetic variation data. We found a clear signal of genetic stratification across the east- west axis within Tibetan samples. Samples from more eastern locations tend to have higher genetic affinity with lowland East Asians, which can be explained by more gene flow from lowland East Asia onto the plateau. Our findings corroborate a previous report of admixture signals in Tibetans, which were based on a subset of the samples analyzed here, but add evidence for isolation by distance in a broader geospatial context

Integration of airborne and ground observations of nitryl chloride in the Seoul metropolitan area and the implications on regional oxidation capacity during KORUS-AQ 2016

Nitryl chloride (ClNO2) is a radical reservoir species that releases chlorine radicals upon photolysis. An integrated analysis of the impact of ClNO2 on regional photochemistry in the Seoul metropolitan area (SMA) during the Korea-United States Air Quality Study (KORUS-AQ) 2016 field campaign is presented. Comprehensive multiplatform observations were conducted aboard the NASA DC-8 and at two ground sites (Olympic Park, OP; Taehwa Research Forest, TRF), representing an urbanized area and a forested suburban region, respectively. Positive correlations between daytime Cl2 and ClNO2 were observed at both sites, the slope of which was dependent on O3 levels. The possible mechanisms are explored through box model simulations constrained with observations. The overall diurnal variations in ClNO2 at both sites appeared similar but the nighttime variations were systematically different. For about half of the observation days at the OP site the level of ClNO2 increased at sunset but rapidly decreased at around midnight. On the other hand, high levels were observed throughout the night at the TRF site. Significant levels of ClNO2 were observed at both sites for 4-5 h after sunrise. Airborne observations, box model calculations, and back-trajectory analysis consistently show that these high levels of ClNO2 in the morning are likely from vertical or horizontal transport of air masses from the west. Box model results show that chlorine-radical-initiated chemistry can impact the regional photochemistry by elevating net chemical production rates of ozone by 25% in the morning

Light Higgsino from Axion Dark Radiation

The recent observations imply that there is an extra relativistic degree of freedom coined dark radiation. We argue that the QCD axion is a plausible candidate for the dark radiation, not only because of its extremely small mass, but also because in the supersymmetric extension of the Peccei-Quinn mechanism the saxion tends to dominate the Universe and decays into axions with a sizable branching fraction. We show that the Higgsino mixing parameter mu is bounded from above when the axions produced at the saxion decays constitute the dark radiation: mu \lesssim 300 GeV for a saxion lighter than 2m_W, and mu less than the saxion mass otherwise. Interestingly, the Higgsino can be light enough to be within the reach of LHC and/or ILC even when the other superparticles are heavy with mass about 1 TeV or higher. We also estimate the abundance of axino produced by the decays of Higgsino and saxion.Comment: 18 pages, 1 figure; published in JHE

String theoretic QCD axions in the light of PLANCK and BICEP2

The QCD axion solving the strong CP problem may originate from antisymmetric tensor gauge fields in compactified string theory, with a decay constant around the GUT scale. Such possibility appears to be ruled out now by the detection of tensor modes by BICEP2 and the PLANCK constraints on isocurvature density perturbations. A more interesting and still viable possibility is that the string theoretic QCD axion is charged under an anomalous U(1)_A gauge symmetry. In such case, the axion decay constant can be much lower than the GUT scale if moduli are stabilized near the point of vanishing Fayet-Illiopoulos term, and U(1)_A-charged matter fields get a vacuum value far below the GUT scale due to a tachyonic SUSY breaking scalar mass. We examine the symmetry breaking pattern of such models during the inflationary epoch with the Hubble expansion rate 10^{14} GeV, and identify the range of the QCD axion decay constant, as well as the corresponding relic axion abundance, consistent with known cosmological constraints. In addition to the case that the PQ symmetry is restored during inflation, there are other viable scenarios, including that the PQ symmetry is broken during inflation at high scales around 10^{16}-10^{17} GeV due to a large Hubble-induced tachyonic scalar mass from the U(1)_A D-term, while the present axion scale is in the range 10^{9}-5\times 10^{13} GeV, where the present value larger than 10^{12} GeV requires a fine-tuning of the axion misalignment angle. We also discuss the implications of our results for the size of SUSY breaking soft masses.Comment: 29 pages, 1 figure; v3: analysis updated including the full anharmonic effects, references added, version accepted for publication in JHE

Beyond the tip of the iceberg: A meta-analysis of the anatomy of the clitoris.

An understanding of ranges in clitoral anatomy is important for clinicians caring for patients including those who have had female genital mutilation, women seeking genital cosmetic surgery, or trans women seeking reconstructive surgery. The aim of this meta-analysis is to investigate the ranges in clitoral measurements within the literature. A meta-analysis was performed on Ovid Medline and Embase databases following the PRISMA protocol. Measurements of clitoral structures from magnetic imaging resonance, ultrasound, cadaveric, and living women were extracted and analyzed. Twenty-one studies met the inclusion criteria. The range in addition to the average length and width of the glans (6.40 mm; 5.14 mm), body (25.46 mm; 9.00 mm), crura (52.41 mm; 8.71 mm), bulb (52.00 mm; 10.33 mm), and prepuce (23.19 mm) was calculated. Furthermore, the range and average distance from the clitoris to the external urethral meatus (22.27 mm), vagina (43.14 mm), and anus (76.30 mm) was documented. All erectile and non-erectile structures of the clitoris present with substantial range. It is imperative to expand the literature on clitoral measurements and disseminate the new results to healthcare professionals and the public to reduce the sense of inadequacy and the chances of iatrogenic damage during surgery

Satellite Data-Based Phenological Evaluation of the Nationwide Reforestation of South Korea

Through the past 60 years, forests, now of various age classes, have been established in the southern part of the Korean Peninsula through nationwide efforts to reestablish forests since the Korean War (1950-53), during which more than 65% of the nation's forest was destroyed. Careful evaluation of long-term changes in vegetation growth after reforestation is one of the essential steps to ensuring sustainable forest management. This study investigated nationwide variations in vegetation phenology using satellite-based growing season estimates for 1982-2008. The start of the growing season calculated from the normalized difference vegetation index (NDVI) agrees reasonably with the ground-observed first flowering date both temporally (correlation coefficient, r = 0.54) and spatially (r = 0.64) at the 95% confidence level. Over the entire 27-year period, South Korea, on average, experienced a lengthening of the growing season of 4.5 days decade(-1), perhaps due to recent global warming. The lengthening of the growing season is attributed mostly to delays in the end of the growing season. The retrieved nationwide growing season data were used to compare the spatial variations in forest biomass carbon density with the time-averaged growing season length for 61 forests. Relatively higher forest biomass carbon density was observed over the regions having a longer growing season, especially for the regions dominated by young (<30 year) forests. These results imply that a lengthening of the growing season related to the ongoing global warming may have positive impacts on carbon sequestration, an important aspect of large-scale forest management for sustainable development.open2

MCL-CAw: A refinement of MCL for detecting yeast complexes from weighted PPI networks by incorporating core-attachment structure

Abstract Background The reconstruction of protein complexes from the physical interactome of organisms serves as a building block towards understanding the higher level organization of the cell. Over the past few years, several independent high-throughput experiments have helped to catalogue enormous amount of physical protein interaction data from organisms such as yeast. However, these individual datasets show lack of correlation with each other and also contain substantial number of false positives (noise). Over these years, several affinity scoring schemes have also been devised to improve the qualities of these datasets. Therefore, the challenge now is to detect meaningful as well as novel complexes from protein interaction (PPI) networks derived by combining datasets from multiple sources and by making use of these affinity scoring schemes. In the attempt towards tackling this challenge, the Markov Clustering algorithm (MCL) has proved to be a popular and reasonably successful method, mainly due to its scalability, robustness, and ability to work on scored (weighted) networks. However, MCL produces many noisy clusters, which either do not match known complexes or have additional proteins that reduce the accuracies of correctly predicted complexes. Results Inspired by recent experimental observations by Gavin and colleagues on the modularity structure in yeast complexes and the distinctive properties of "core" and "attachment" proteins, we develop a core-attachment based refinement method coupled to MCL for reconstruction of yeast complexes from scored (weighted) PPI networks. We combine physical interactions from two recent "pull-down" experiments to generate an unscored PPI network. We then score this network using available affinity scoring schemes to generate multiple scored PPI networks. The evaluation of our method (called MCL-CAw) on these networks shows that: (i) MCL-CAw derives larger number of yeast complexes and with better accuracies than MCL, particularly in the presence of natural noise; (ii) Affinity scoring can effectively reduce the impact of noise on MCL-CAw and thereby improve the quality (precision and recall) of its predicted complexes; (iii) MCL-CAw responds well to most available scoring schemes. We discuss several instances where MCL-CAw was successful in deriving meaningful complexes, and where it missed a few proteins or whole complexes due to affinity scoring of the networks. We compare MCL-CAw with several recent complex detection algorithms on unscored and scored networks, and assess the relative performance of the algorithms on these networks. Further, we study the impact of augmenting physical datasets with computationally inferred interactions for complex detection. Finally, we analyse the essentiality of proteins within predicted complexes to understand a possible correlation between protein essentiality and their ability to form complexes. Conclusions We demonstrate that core-attachment based refinement in MCL-CAw improves the predictions of MCL on yeast PPI networks. We show that affinity scoring improves the performance of MCL-CAw.http://deepblue.lib.umich.edu/bitstream/2027.42/78256/1/1471-2105-11-504.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/2/1471-2105-11-504-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/3/1471-2105-11-504-S2.ZIPhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/4/1471-2105-11-504.pdfPeer Reviewe

Shigella sonnei genome sequencing and phylogenetic analysis indicate recent global dissemination from Europe

Shigella are human-adapted Escherichia coli that have gained the ability to invade the human gut mucosa and cause dysentery1,2, spreading efficiently via low-dose fecal-oral transmission3,4. Historically, S. sonnei has been predominantly responsible for dysentery in developed countries, but is now emerging as a problem in the developing world, apparently replacing the more diverse S. flexneri in areas undergoing economic development and improvements in water quality4-6. Classical approaches have shown S. sonnei is genetically conserved and clonal7. We report here whole-genome sequencing of 132 globally-distributed isolates. Our phylogenetic analysis shows that the current S. sonnei population descends from a common ancestor that existed less than 500 years ago and has diversified into several distinct lineages with unique characteristics. Our analysis suggests the majority of this diversification occurred in Europe, followed by more recent establishment of local pathogen populations in other continents predominantly due to the pandemic spread of a single, rapidly-evolving, multidrug resistant lineage