1,042 research outputs found

    Evidence for the prepattern/cooption model of vertebrate jaw evolution

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    The appearance of jaws was a turning point in vertebrate evolution because it allowed primitive vertebrates to capture and process large, motile prey. The vertebrate jaw consists of separate dorsal and ventral skeletal elements connected by a joint. How this structure evolved from the unjointed gill bar of a jawless ancestor is an unresolved question in vertebrate evolution. To understand the developmental bases of this evolutionary transition, we examined the expression of 12 genes involved in vertebrate pharyngeal patterning in the modern jawless fish lamprey. We find nested expression of Dlx genes, as well as combinatorial expression of Msx, Hand and Gsc genes along the dorso-ventral (DV) axis of the lamprey pharynx, indicating gnathostome-type pharyngeal patterning evolved before the appearance of the jaw. In addition, we find that Bapx and Gdf5/6/7, key regulators of joint formation in gnathostomes, are not expressed in the lamprey first arch, whereas Barx, which is absent from the intermediate first arch in gnathostomes, marks this domain in lamprey. Taken together, these data support a new scenario for jaw evolution in which incorporation of Bapx and Gdf5/6/7 into a preexisting DV patterning program drove the evolution of the jaw by altering the identity of intermediate first-arch chondrocytes. We present this “Pre-pattern/Cooption” model as an alternative to current models linking the evolution of the jaw to the de novo appearance of sophisticated pharyngeal DV patterning

    The Use of HCG‐Based Combination Therapy for Recovery of Spermatogenesis after Testosterone Use

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    Introduction and AimAbout 3 million men take testosterone in the United States with many reproductive‐age men unaware of the negative impact of testosterone supplementation on fertility. Addressing this population, we provide an early report on the use of human chorionic gonadotropin (HCG)‐based combination therapy in the treatment of a series of men with likely testosterone‐related azoospermia or severe oligospermia. MethodsWe retrospectively reviewed charts from two tertiary care infertility clinics to identify men presenting with azoospermia or severe oligospermia (<1 million sperm/mL) while taking exogenous testosterone. All were noted to have been placed on combination therapy, which included 3,000 units HCG subcutaneously every other day supplemented with clomiphene citrate, tamoxifen, anastrozole, or recombinant follicle‐stimulating hormone (or combination) according to physician preference.Main Outcome MeasureClinical outcomes, including hormone values, semen analyses, and clinical pregnancies, were tracked. ResultsForty‐nine men were included in this case series. Return of spermatogenesis for azoospermic men or improved counts for men with severe oligospermia was documented in 47 men (95.9%), with one additional man (2.1%) having a documented pregnancy without follow‐up semen analysis. The average time to return of spermatogenesis was 4.6 months with a mean first density of 22.6 million/mL. There was no significant difference in recovery by type of testosterone administered or supplemental therapy. No men stopped HCG or supplemental medications because of adverse events. ConclusionsWe here provide an early report of the feasibility of using combination therapy with HCG and supplemental medications in treating men with testosterone‐related infertility. Future discussion and studies are needed to further characterize this therapeutic approach and document the presumed improved tolerability and speed of recovery compared with unaided withdrawal of exogenous testosterone. Wenker EP, Dupree JM, Langille GM, Kovac J, Ramasamy R, Lamb D, Mills JN, and Lipshultz LI. The use of HCG‐based combination therapy for recovery of spermatogenesis after testosterone use. J Sex Med 2015;12:1334–1337.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111925/1/jsm12890.pd

    Simple gene assembly as a rewriting of directed overlap-inclusion graphs

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    The simple intramolecular model for gene assembly in ciliates consists of three molecular operations, simple Id, simple hi and simple dlad. Mathematical models in terms of signed permutations and signed strings proved limited in capturing some of the combinatorial details of the simple gene assembly process. Brijder and Hoogeboom introduced a new model in terms of overlap-inclusion graphs which could describe two of the three operations of the model and their combinatorial properties. To capture the third operation, we extended their framework to directed overlap-inclusion (DOI) graphs in Azimi et al. (2011) [1]. In this paper we introduce DOI graph-based rewriting rules that capture all three operations of the simple gene assembly model and prove that they are equivalent to the string-based formalization of the model. (C) 2012 Elsevier B.V. All rights reserved

    G(alpha)11 signaling through ARF6 regulates F-actin mobilization and GLUT4 glucose transporter translocation to the plasma membrane

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    The action of insulin to recruit the intracellular GLUT4 glucose transporter to the plasma membrane of 3T3-L1 adipocytes is mimicked by endothelin 1, which signals through trimeric G(alpha)q or G(alpha)11 proteins. Here we report that murine G(alpha)11 is most abundant in fat and that expression of the constitutively active form of G(alpha)11 [G(alpha)11(Q209L)] in 3T3-L1 adipocytes causes recruitment of GLUT4 to the plasma membrane and stimulation of 2-deoxyglucose uptake. In contrast to the action of insulin on GLUT4, the effects of endothelin 1 and G(alpha)11 were not inhibited by the phosphatidylinositol 3-kinase inhibitor wortmannin at 100 nM. Signaling by insulin, endothelin 1, or G(alpha)11(Q209L) also mobilized cortical F-actin in cultured adipocytes. Importantly, GLUT4 translocation caused by all three agents was blocked upon disassembly of F-actin by latrunculin B, suggesting that the F-actin polymerization caused by these agents may be required for their effects on GLUT4. Remarkably, expression of a dominant inhibitory form of the actin-regulatory GTPase ARF6 [ARF6(T27N)] in cultured adipocytes selectively inhibited both F-actin formation and GLUT4 translocation in response to endothelin 1 but not insulin. These data indicate that ARF6 is a required downstream element in endothelin 1 signaling through G(alpha)11 to regulate cortical actin and GLUT4 translocation in cultured adipocytes, while insulin action involves different signaling pathways

    New Cryogenian, Neoproterozoic, and middle Paleozoic U–Pb zircon ages from the Caledonia terrane, southern New Brunswick, Canada: better constrained but more complex volcanic stratigraphy

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    New U–Pb zircon ages from volcanic, plutonic, and sedimentary units in the Avalonian Caledonia terrane of southern New Brunswick provide better timing constraints in this geologically complex area. Previous ca. 620 Ma ages from the Broad River Group are now corroborated by additional dates from felsic tuff in the Gordon Falls Formation and rhyolite in the former Fairfield (now East Branch Black River) Formation of 620 ± 5 Ma and 622 ± 1.9 Ma, respectively. Combined with ages ranging from ca. 625 Ma to 615 Ma from crosscutting plutons, the data suggest that the minimum age of the Broad River Group is about 615 Ma. A quartzfeldspar porphyry dyke in mafic volcanic rocks of the previously undated Long Beach Formation yielded an igneous crystallization age of 685 ± 10 Ma, the oldest unit yet dated in the Caledonia terrane but similar in age to porphyry in the Stirling belt in the Avalonian Mira terrane of Nova Scotia. The age of the Coldbrook Group was constrained previously by U–Pb (zircon) ages of volcanic rocks between 560 and 550 Ma as well as by similar ages from comagmatic plutons. Five additional samples from both volcanic and plutonic units lie in the same range of 560–550 Ma, including errors, demonstrating that the Coldbrook Group and related plutons formed in less than 10 million years. Such a large volume of mainly felsic magma erupted and emplaced in a short time span suggests a “supereruption/supervolcano” environment such as the late Cenozoic southwestern USA but not yet recognized at ca. 560–550 Ma elsewhere in Avalonia. Two units yielded Paleozoic ages: felsite of the Bloomsbury Mountain Formation with a zircon population at 427 ± 9 Ma, indicating a Silurian maximum emplacement age, and dacite of the Grassy Lake Formation with several zircon grains at 382.8 ± 8.3 Ma, indicating a maximum age of middle Devonian, the first rocks of this age to be identified in the Caledonia terrane

    Detection of Helicobacter pylori Microevolution and Multiple Infection from Gastric Biopsies by Housekeeping Gene Amplicon Sequencing

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    Despite the great efforts devoted to research on Helicobacter pylori, the prevalence of single-strain infection or H. pylori mixed infection and its implications in the mode of transmission of this bacterium are still controversial. In this study, we explored the usefulness of housekeeping gene amplicon sequencing in the detection of H. pylori microevolution and multiple infections. DNA was extracted from five gastric biopsies from four patients infected with distinct histopathological diagnoses. PCR amplification of six H. pylori-specific housekeeping genes was then assessed on each sample. Optimal results were obtained for the cgt and luxS genes, which were selected for amplicon sequencing. A total of 11,833 cgt and 403 luxS amplicon sequences were obtained, 2042 and 112 of which were unique sequences, respectively. All cgt and luxS sequences were clustered at 97% to 9 and 13 operational taxonomic units (OTUs), respectively. For each sample from a different patient, a single OTU comprised the majority of sequences in both genes, but more than one OTU was detected in all samples. These results suggest that multiple infections with a predominant strain together with other minority strains are the main way by which H. pylori colonizes the human stomach
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