1,3-Dimethyl­benzo[b]dibenzothio­phene

The molecule of the title compound, C18H14S, is approximately planar (r.m.s. deviation = 0.029 Å). The crystal packing is stabilized by weak inter­molecular C—H⋯π inter­actions

Integrating Extrinsic and Intrinsic Cues into a Minimal Model of Lineage Commitment for Hematopoietic Progenitors

Autoregulation of transcription factors and cross-antagonism between lineage-specific transcription factors are a recurrent theme in cell differentiation. An equally prevalent event that is frequently overlooked in lineage commitment models is the upregulation of lineage-specific receptors, often through lineage-specific transcription factors. Here, we use a minimal model that combines cell-extrinsic and cell-intrinsic elements of regulation in order to understand how both instructive and stochastic events can inform cell commitment decisions in hematopoiesis. Our results suggest that cytokine-mediated positive receptor feedback can induce a “switch-like” response to external stimuli during multilineage differentiation by providing robustness to both bipotent and committed states while protecting progenitors from noise-induced differentiation or decommitment. Our model provides support to both the instructive and stochastic theories of commitment: cell fates are ultimately driven by lineage-specific transcription factors, but cytokine signaling can strongly bias lineage commitment by regulating these inherently noisy cell-fate decisions with complex, pertinent behaviors such as ligand-mediated ultrasensitivity and robust multistability. The simulations further suggest that the kinetics of differentiation to a mature cell state can depend on the starting progenitor state as well as on the route of commitment that is chosen. Lastly, our model shows good agreement with lineage-specific receptor expression kinetics from microarray experiments and provides a computational framework that can integrate both classical and alternative commitment paths in hematopoiesis that have been observed experimentally

Antisperm Antibody Testing: A Comprehensive Review of Its Role in the Management of Immunological Male Infertility and Results of a Global Survey of Clinical Practices

Antisperm antibodies (ASA), as a cause of male infertility, have been detected in infertile males as early as 1954. Multiple causes of ASA production have been identified, and they are due to an abnormal exposure of mature germ cells to the immune system. ASA testing (with mixed anti-globulin reaction, and immunobead binding test) was described in the WHO manual 5th edition and is most recently listed among the extended semen tests in the WHO manual 6th edition. The relationship between ASA and infertility is somewhat complex. The presence of sperm agglutination, while insufficient to diagnose immunological infertility, may indicate the presence of ASA. However, ASA can also be present in the absence of any sperm agglutination. The andrological management of ASA depends on the etiology and individual practices of clinicians. In this article, we provide a comprehensive review of the causes of ASA production, its role in immunological male infertility, clinical indications of ASA testing, and the available therapeutic options. We also provide the details of laboratory procedures for assessment of ASA together with important measures for quality control. Additionally, laboratory and clinical scenarios are presented to guide the reader in the management of ASA and immunological male infertility. Furthermore, we report the results of a recent worldwide survey, conducted to gather information about clinical practices in the management of immunological male infertility

Expression of the chemokine receptor CCR5 in psoriasis and results of a randomized placebo controlled trial with a CCR5 inhibitor

Several reports have indicated that the chemokine receptor CCR5 and its ligands, especially CCL5 (formerly known as RANTES), may play a role in the pathogenesis of psoriasis. The purpose of this investigation was to examine the expression of CCR5 and its ligands in chronic plaque psoriasis and to evaluate the clinical and immunohistochemical effect of a CCR5 receptor inhibitor. Immunohistochemical analysis showed low but significant increased total numbers of CCR5 positive cells in epidermis and dermis of lesional skin in comparison to non-lesional skin. However, relative expression of CCR5 proportional to the cells observed revealed that the difference between lesional and non-lesional skin was only statistically significant in the epidermis for CD3 positive cells and in the dermis for CD68 positive cells. Quantification of mRNA by reverse transcriptase-polymerase chain reaction only showed an increased expression of CCL5 (RANTES) in lesional skin. A randomized placebo-controlled clinical trial in 32 psoriasis patients revealed no significant clinical effect and no changes at the immunohistochemical level comparing patients treated with placebo or a CCR5 inhibitor SCH351125. We conclude that although CCR5 expression is increased in psoriatic lesions, this receptor does not play a crucial role in the pathogenesis of psoriasis

Controversy and consensus on the management of elevated sperm DNA fragmentation in male infertility: a global survey, current guidelines, and expert recommendations

PURPOSE: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. MATERIALS AND METHODS: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method. RESULTS: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4-6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. CONCLUSIONS: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians

Controversy and consensus on indications for sperm DNA fragmentation testing in male infertility: a global survey, current guidelines, and expert recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. MATERIALS AND METHODS: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. RESULTS: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. CONCLUSIONS: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians

Fungal Planet description sheets: 1284–1382

Novel species of fungi described in this study include those from various countries as follows: Antartica, Cladosporium austrolitorale from coastal sea sand. Australia, Austroboletus yourkae on soil, Crepidotus innuopurpureus on dead wood, Curvularia stenotaphri from roots and leaves of Stenotaphrum secundatum and Thecaphora stajsicii from capsules of Oxalis radicosa. Belgium, Paraxerochrysium coryli (incl. Paraxerochrysium gen. nov.) from Corylus avellana. Brazil, Calvatia nordestina on soil, Didymella tabebuiicola from leaf spots on Tabebuia aurea, Fusarium subflagellisporum from hypertrophied floral and vegetative branches of Mangifera indica and Microdochium maculosum from living leaves of Digitaria insularis. Canada, Cuphophyllus bondii fromagrassland. Croatia, Mollisia inferiseptata from a rotten Laurus nobilis trunk. Cyprus, Amanita exilis oncalcareoussoil. Czech Republic, Cytospora hippophaicola from wood of symptomatic Vaccinium corymbosum. Denmark, Lasiosphaeria deviata on pieces of wood and herbaceousdebris. Dominican Republic, Calocybella goethei among grass on a lawn. France (Corsica) , Inocybe corsica onwetground. France (French Guiana) , Trechispora patawaensis on decayed branch of unknown angiosperm tree and Trechispora subregularis on decayed log of unknown angiosperm tree. Germany, Paramicrothecium sambuci (incl. Paramicrothecium gen. nov.)ondeadstemsof Sambucus nigra. India, Aureobasidium microtermitis from the gut of a Microtermes sp. termite, Laccaria diospyricola on soil and Phylloporia tamilnadensis on branches of Catunaregam spinosa. Iran, Pythium serotinoosporum from soil under Prunus dulcis. Italy, Pluteus brunneovenosus on twigs of broad leaved trees on the ground. Japan, Heterophoma rehmanniae on leaves of Rehmannia glutinosa f. hueichingensis. Kazakhstan, Murispora kazachstanica from healthy roots of Triticum aestivum. Namibia, Caespitomonium euphorbiae (incl. Caespitomonium gen. nov.)from stems of an Euphorbia sp. Netherlands, Alfaria junci, Myrmecridium junci, Myrmecridium juncicola, Myrmecridium juncigenum, Ophioceras junci, Paradinemasporium junci (incl. Paradinemasporium gen. nov.), Phialoseptomonium junci, Sporidesmiella juncicola, Xenopyricularia junci and Zaanenomyces quadripartis (incl. Zaanenomyces gen. nov.), fromdeadculmsof Juncus effusus, Cylindromonium everniae and Rhodoveronaea everniae from Evernia prunastri, Cyphellophora sambuci and Myrmecridium sambuci from Sambucus nigra, Kiflimonium junci, Saro cladium junci, Zaanenomyces moderatricis academiae and Zaanenomyces versatilis from dead culms of Juncus inflexus, Microcera physciae from Physcia tenella, Myrmecridium dactylidis from dead culms of Dactylis glomerata, Neochalara spiraeae and Sporidesmium spiraeae from leaves of Spiraea japonica, Neofabraea salicina from Salix sp., Paradissoconium narthecii (incl. Paradissoconium gen. nov.)from dead leaves of Narthecium ossifragum, Polyscytalum vaccinii from Vaccinium myrtillus, Pseudosoloacrosporiella cryptomeriae (incl. Pseudosoloacrosporiella gen. nov.)fromleavesof Cryptomeria japonica, Ramularia pararhabdospora from Plantago lanceolata, Sporidesmiella pini from needles of Pinus sylvestris and Xenoacrodontium juglandis (incl. Xenoacrodontium gen. nov. and Xenoacrodontiaceae fam. nov.)from Juglans regia. New Zealand, Cryptometrion metrosideri from twigs of Metrosideros sp., Coccomyces pycnophyllocladi from dead leaves of Phyllocladus alpinus, Hypoderma aliforme from fallen leaves Fuscopora solandri and Hypoderma subiculatum from dead leaves Phormium tenax. Norway, Neodevriesia kalakoutskii from permafrost and Variabilispora viridis from driftwood of Picea abies. Portugal, Entomortierella hereditatis from abio film covering adeteriorated limestone wall. Russia, Colpoma junipericola from needles of Juniperus sabina, Entoloma cinnamomeum on soil in grasslands, Entoloma verae on soil in grasslands, Hyphodermella pallidostraminea on a dry dead branch of Actinidia sp., Lepiota sayanensis onlitterinamixedforest, Papiliotrema horticola from Malus communis , Paramacroventuria ribis (incl. Paramacroventuria gen. nov.)fromleaves of Ribes aureum and Paramyrothecium lathyri from leaves of Lathyrus tuberosus. South Africa, Harzia combreti from leaf litter of Combretum collinum ssp. sulvense, Penicillium xyleborini from Xyleborinus saxesenii , Phaeoisaria dalbergiae from bark of Dalbergia armata, Protocreopsis euphorbiae from leaf litter of Euphorbia ingens and Roigiella syzygii from twigs of Syzygium chordatum. Spain, Genea zamorana on sandy soil, Gymnopus nigrescens on Scleropodium touretii, Hesperomyces parexochomi on Parexochomus quadriplagiatus, Paraphoma variabilis from dung, Phaeococcomyces kinklidomatophilus from a blackened metal railing of an industrial warehouse and Tuber suaveolens in soil under Quercus faginea. Svalbard and Jan Mayen, Inocybe nivea associated with Salix polaris. Thailand, Biscogniauxia whalleyi oncorticatedwood. UK, Parasitella quercicola from Quercus robur. USA , Aspergillus arizonicus from indoor air in a hospital, Caeliomyces tampanus (incl. Caeliomyces gen. nov.)fromoffice dust, Cippumomyces mortalis (incl. Cippumomyces gen. nov.)fromatombstone, Cylindrium desperesense from air in a store, Tetracoccosporium pseudoaerium from air sample in house, Toxicocladosporium glendoranum from air in a brick room, Toxicocladosporium losalamitosense from air in a classroom, Valsonectria portsmouthensis from airinmen'slockerroomand Varicosporellopsis americana from sludge in a water reservoir. Vietnam, Entoloma kovalenkoi on rotten wood, Fusarium chuoi inside seed of Musa itinerans , Micropsalliota albofelina on soil in tropical evergreen mixed forest sand Phytophthora docyniae from soil and roots of Docynia indica. Morphological and culture characteristics are supported by DNA barcodes

Micropropagation and conservation of selected endangered anticancer medicinal plants from the Western Ghats of India

Globally, cancer is a constant battle which severely affects the human population. The major limitations of the anticancer drugs are the deleterious side effects on the quality of life. Plants play a vital role in curing many diseases with minimal or no side effects. Phytocompounds derived from various medicinal plants serve as the best source of drugs to treat cancer. The global demand for phytomedicines is mostly reached by the medicinal herbs from the tropical nations of the world even though many plant species are threatened with extinction. India is one of the mega diverse countries of the world due to its ecological habitats, latitudinal variation, and diverse climatic range. Western Ghats of India is one of the most important depositories of endemic herbs. It is found along the stretch of south western part of India and constitutes rain forest with more than 4000 diverse medicinal plant species. In recent times, many of these therapeutically valued herbs have become endangered and are being included under the red-listed plant category in this region. Due to a sharp rise in the demand for plant-based products, this rich collection is diminishing at an alarming rate that eventually triggered dangerous to biodiversity. Thus, conservation of the endangered medicinal plants has become a matter of importance. The conservation by using only in situ approaches may not be sufficient enough to safeguard such a huge bio-resource of endangered medicinal plants. Hence, the use of biotechnological methods would be vital to complement the ex vitro protection programs and help to reestablish endangered plant species. In this backdrop, the key tools of biotechnology that could assist plant conservation were developed in terms of in vitro regeneration, seed banking, DNA storage, pollen storage, germplasm storage, gene bank (field gene banking), tissue bank, and cryopreservation. In this chapter, an attempt has been made to critically review major endangered medicinal plants that possess anticancer compounds and their conservation aspects by integrating various biotechnological tool