Haplotype Structure of FSHB, the Beta-Subunit Gene for Fertility-Associated Follicle-Stimulating Hormone: Possible Influence of Balancing Selection

Follicle-stimulating hormone (FSH) is essential for human reproduction. The unique functions of this hormone are provided by the FSH receptor-binding beta-subunit encoded by the FSHB gene. Resequencing and genotyping of FSHB in three European, two Asian and one African population, as well as in the great apes (chimpanzee, gorilla, orangutan), revealed low diversity and significant excess of polymorphisms with intermediate frequency alleles. Statistical tests for FSHB showed deviations from neutrality in all populations suggesting a possible effect of balancing selection. Two core haplotypes were identified (carried by 76-96.6% of each population's sample), the sequences of which are clearly separated from each other. As fertility most directly affects an organism's fitness, the carriers of these haplotypes have apparently had more success in human history to contribute to the next generation. There is a preliminary observation suggesting that the second most frequent FSHB haplotype may be associated with rapid conception success in females. Interestingly, the same haplotype is related to an ancestral FSHB variant shared with the ancestor of the great apes. The determination of the functional consequence of the two core FSHB variants may have implications for understanding and regulating human fertility, as well as in assisting infertility treatments

Fall, classification and cosmogenic records of the Sabrum (LL6) chondrite

The petrographic and chemical characteristics of a fresh Indian meteorite fall at Sabrum are described. Its mean mineral composition is defined by olivine (Fa31.4), orthopyroxene (Fs25.1,Wo2.0), clinopyroxene (Wo45En45.6Fs9.4) and plagioclase (An10.6Ab83.6Or5.8). The meteorite shows moderate shock features, which indicate that it belongs to the S4 category. Based on mineralogical and chemical criteria the meteorite is classified as an LL6 brecciated veined chondrite. Several cosmogenic radioisotopes (46Sc, 7Be, 54Mn, 22Na and 26Al), noble gas (He, Ne, Ar, Kr and Xe), nitrogen isotopes, and particle tracks density have been measured. Concentrations of cosmogenic 21Ne and 38Ar indicate that its cosmic-ray exposure age is 24.8 Ma. Small amounts of trapped Kr and Xe, consistent with petrologic class 5/6, are present. The track density in olivines is found to be (1.3 ± 0.3) × 106/cm2. Activities of most of the short-lived isotopes are lower than those expected from solar cycle variation. 22Na/26Al (1.12 ± 0.02) is found to be significantly anomalous, being ~25% lower than expected from the Climax neutron monitor data. These results indicate that the cosmic-ray flux during the terminal segment of the meteoroid orbit was low. The activities of 26Al and 60Co and the track density indicate small meteoroid size with a radius ~15 cm

Renal cell carcinoma metastasis to the ciliary body responds to proton beam radiotherapy: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report an unexpected presentation of metastatic renal cell carcinoma (RCC) to the ciliary body and an interesting response to proton beam radiotherapy.</p> <p>Case presentation</p> <p>We encountered a case of angle-closure glaucoma as the initial presentation of ocular metastasis to the ciliary body in a 65-year-old Caucasian man who had undergone right radical nephrectomy for RCC 15 years earlier. He underwent YAG (yttrium aluminium garnet) laser peripheral iridotomy while further metastatic workup took place. His condition was eventually diagnosed as stage IV metastatic RCC of the clear cell type and involved multiple sites, including the ciliary body, brain, lungs, liver, and pancreas. The progression of RCC metastasis to the ciliary body was studied for 16 months. The ciliary body mass continued to grow despite systemic treatment with temsirolimus and interleukin-2 and intravitreal injections of bevacizumab. The tumor size peaked at 6.11 × 6.06 mm before the start of proton therapy, which reduced the tumor size to 5.07 × 4.39 mm.</p> <p>Conclusions</p> <p>RCC can produce metastases involving unusual sites many years after resection of the primary tumor. Proton therapy was found to be effective in treating RCC metastasis to the ciliary body in settings in which other treatment modalities failed.</p

Predictors of 1- and 12-month mortality in bifurcation coronary intervention: a contemporary perspective

Aim: Bifurcation-PCI is performed frequently, although without extensive evidence to back up a definitive solution for its complexity. We set out to identify factors associated with 1- and 12-month mortality after bifurcation-PCI between 2017 and 2021 in our tertiary centre in Wales, UK. Results: Of 732 bifurcation PCI cases (mean age 69; 25% female), 67% were in ACS, 42% were left main PCI and 25.3% involved two-stent strategy. 30-day and 12-month mortality were 1.9% and 8.2%, respectively. Age, diabetes, smoking and renal failure are associated with mortality after bifurcation-PCI, while the choice between provisional and 2-stent strategies did not impact mortality/TLR. Conclusion: Awareness of ‘real-world’ outcomes of bifurcation-PCI should be used for appropriate patient selection, technique planning and procedural consent

Dopamine Regulates Mobilization of Mesenchymal Stem Cells during Wound Angiogenesis

Angiogenesis is an important step in the complex biological and molecular events leading to successful healing of dermal wounds. Among the different cellular effectors of wound angiogenesis, the role of mesenchymal stem cells (MSCs) is of current interest due to their transdifferentiation and proangiogenic potentials. Skin is richly innervated by sympathetic nerves which secrete dopamine (DA) and we have recently shown that concentration of DA present in synaptic cleft can significantly inhibit wound tissue neovascularization. As recent reports indicate that MSCs by mobilizing into wound bed play an important role in promoting wound angiogenesis, we therefore investigated the effect of DA on the migration of MSCs in wound tissues. DA acted through its D2 receptors present in the MSCs to inhibit their mobilization to the wound beds by suppressing Akt phosphorylation and actin polymerization. In contrast, this inhibitory effect of DA was reversed after treatment with specific DA D2 receptor antagonist. Increased mobilization of MSCs was demonstrated in the wound site following blockade of DA D2 receptor mediated actions, and this in turn was associated with significantly more angiogenesis in wound tissues. This study is of translational value and indicates use of DA D2 receptor antagonists to stimulate mobilization of these stem cells for faster regeneration of damaged tissues

Phospholipase D signaling: orchestration by PIP2 and small GTPases

Hydrolysis of phosphatidylcholine by phospholipase D (PLD) leads to the generation of the versatile lipid second messenger, phosphatidic acid (PA), which is involved in fundamental cellular processes, including membrane trafficking, actin cytoskeleton remodeling, cell proliferation and cell survival. PLD activity can be dramatically stimulated by a large number of cell surface receptors and is elaborately regulated by intracellular factors, including protein kinase C isoforms, small GTPases of the ARF, Rho and Ras families and, particularly, by the phosphoinositide, phosphatidylinositol 4,5-bisphosphate (PIP2). PIP2 is well known as substrate for the generation of second messengers by phospholipase C, but is now also understood to recruit and/or activate a variety of actin regulatory proteins, ion channels and other signaling proteins, including PLD, by direct interaction. The synthesis of PIP2 by phosphoinositide 5-kinase (PIP5K) isoforms is tightly regulated by small GTPases and, interestingly, by PA as well, and the concerted formation of PIP2 and PA has been shown to mediate receptor-regulated cellular events. This review highlights the regulation of PLD by membrane receptors, and describes how the close encounter of PLD and PIP5K isoforms with small GTPases permits the execution of specific cellular functions

Palaeobiology of latest Ediacaran phosphorites from the upper Khesen Formation, Khuvsgul Group, northern Mongolia

Microfossil assemblages that include large acritarchs with complex processes, known as Doushantuo-Pertatataka-type acritarchs, are recovered from early Ediacaran successions globally. They are commonly found in shale and chert lithologies, but their diversity and palaeobiological significance is greatest when they are phosphatized. The best-known examples are from the Doushantuo Formation, South China, which preserves over 60 taxa including possible embryonic forms which may represent the oldest fossil animals. Fossils have only been recorded in four Ediacaran phosphorite deposits. Here we report the fifth such occurrence, from phosphorites of the upper Khesen Formation, Khuvsgul Group, northern Mongolia, where preservation rivals that in the Doushantuo Formation. The assemblage includes the likely cyanobacteria Obruchevella delicata, O. magna, O. parvissima and O. valdaica, as well as various Siphonophycus filaments, the possible alga Archaeophycus yunnanensis, and the Doushantuo-Pertatataka-type acritarchs Appendisphaera grandis, A. fragilis, A. tenuis, Cavaspina basiconica, Variomargosphaeridium gracile and V. aculeiparvum, sp. nov. The phosphorites also preserve the multicellular embryo-like taxon Megasphaera, which is represented by M. minuscula sp. nov. and potentially by M. puncticulosa. Geological and chemostratigraphical data suggest a latest Ediacaran age for the Khesen assemblage, immediately prior to the Proterozoic–Phanerozoic boundary. Thus, this is the youngest Doushantuo-Pertatataka-type microfossil assemblage yet described. It extends the range of Appendisphaera, Cavaspina, Megasphaera and Variomargosphaeridium upward by tens of millions of years. The assemblage adds to a growing database of Ediacaran fossils and emphasizes the importance of Mongolian strata to understanding the transition from a broadly microbial Proterozoic Eon to a Phanerozoic Eon where macroscopic animals acted as geobiological agents

<smarttagtype namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="place"> Microbial L–asparaginase from mangroves of Andaman Islands </smarttagtype>

183-184Bacterial strains from mangroves of Andamans were assayed for L-asparaginase enzyme. One hundred and eight (54%), of total 200, isolates synthesized L–asparaginase, growing at pH 7.2 and 37°C temperature. Only two gram negative strains appeared to be potent for large-scale production

Bacterial flora in mangroves of Andaman – Part-I : Isolation, identification and antibiogram studies

97-98Bacterial flora of mangrove litter fall and underneath sediments froIn South Andaman was investigated. Thirtyeight bacterial isolates were obtained from Rhizophora, Avicennia and Nypa species inhabited areas. The cultural, morphological and biochemical features revealed that most of the isolates belong to Bacillus spp (50%). In addition Aeromonas, Vibrio, Escherichia, Enterobacter, Corynaebacterium, Kurthia, Staphyllococcus, Micrococcus, and Listeria were also present. Most isolates were gram positive (76.3%), motile (87%) and fermentative bacteria ranged from 6.9% for dulcitol to 82.1% for dextrose. Thirty per cent isolates were pigment producer (either diffusible or cell associated). The bacterial isolates showed a minimum of 50% resistance against chloramphenicol and a maximum of 100% resistance against polymixin B