Fungal Planet description sheets: 1383-1435.

Novel species of fungi described in this study include those from various countries as follows: Australia, Agaricus albofoetidus, Agaricus aureoelephanti and Agaricus parviumbrus on soil, Fusarium ramsdenii from stem cankers of Araucaria cunninghamii, Keissleriella sporoboli from stem of Sporobolus natalensis, Leptosphaerulina queenslandica and Pestalotiopsis chiaroscuro from leaves of Sporobolus natalensis, Serendipita petricolae as endophyte from roots of Eriochilus petricola, Stagonospora tauntonensis from stem of Sporobolus natalensis, Teratosphaeria carnegiei from leaves of Eucalyptus grandis × E. camaldulensis and Wongia ficherai from roots of Eragrostis curvula. Canada, Lulworthia fundyensis from intertidal wood and Newbrunswickomyces abietophilus (incl. Newbrunswickomyces gen. nov.) on buds of Abies balsamea. Czech Republic, Geosmithia funiculosa from a bark beetle gallery on Ulmus minor and Neoherpotrichiella juglandicola (incl. Neoherpotrichiella gen. nov.) from wood of Juglans regia. France, Aspergillus rouenensis and Neoacrodontium gallica (incl. Neoacrodontium gen. nov.) from bore dust of Xestobium rufovillosum feeding on Quercus wood, Endoradiciella communis (incl. Endoradiciella gen. nov.) endophytic in roots of Microthlaspi perfoliatum and Entoloma simulans on soil. India, Amanita konajensis on soil and Keithomyces indicus from soil. Israel, Microascus rothbergiorum from Stylophora pistillata. Italy, Calonarius ligusticus on soil. Netherlands, Appendopyricularia juncicola (incl. Appendopyricularia gen. nov.), Eriospora juncicola and Tetraploa juncicola on dead culms of Juncus effusus, Gonatophragmium physciae on Physcia caesia and Paracosmospora physciae (incl. Paracosmospora gen. nov.) on Physcia tenella, Myrmecridium phragmitigenum on dead culm of Phragmites australis, Neochalara lolae on stems of Pteridium aquilinum, Niesslia nieuwwulvenica on dead culm of undetermined Poaceae, Nothodevriesia narthecii (incl. Nothodevriesia gen. nov.) on dead leaves of Narthecium ossifragum and Parastenospora pini (incl. Parastenospora gen. nov.) on dead twigs of Pinus sylvestris. Norway, Verticillium bjoernoeyanum from sand grains attached to a piece of driftwood on a sandy beach. Portugal, Collybiopsis cimrmanii on the base of living Quercus ilex and amongst dead leaves of Laurus and herbs. South Africa, Paraproliferophorum hyphaenes (incl. Paraproliferophorum gen. nov.) on living leaves of Hyphaene sp. and Saccothecium widdringtoniae on twigs of Widdringtonia wallichii. Spain, Cortinarius dryosalor on soil, Cyphellophora endoradicis endophytic in roots of Microthlaspi perfoliatum, Geoglossum lauri-silvae on soil, Leptographium gemmatum from fluvial sediments, Physalacria auricularioides from a dead twig of Castanea sativa, Terfezia bertae and Tuber davidlopezii in soil. Sweden, Alpova larskersii, Inocybe alpestris and Inocybe boreogodeyi on soil. Thailand, Russula banwatchanensis, Russula purpureoviridis and Russula lilacina on soil. Ukraine, Nectriella adonidis on overwintered stems of Adonis vernalis. USA, Microcyclus jacquiniae from living leaves of Jacquinia keyensis and Penicillium neoherquei from a minute mushroom sporocarp. Morphological and culture characteristics are supported by DNA barcodes. Citation: Crous PW, Boers J, Holdom D, et al. 2022. Fungal Planet description sheets: 1383-1435. Persoonia 48: 261-371. https://doi.org/10.3767/persoonia.2022.48.08.

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 from a grassland. Croatia, Mollisia inferiseptata from a rotten Laurus nobilis trunk. Cyprus, Amanita exilis on calcareous soil. Czech Republic, Cytospora hippophaicola from wood of symptomatic Vaccinium corymbosum. Denmark, Lasiosphaeria deviata on pieces of wood and herbaceous debris. Dominican Republic, Calocybella goethei among grass on a lawn. France (Corsica), Inocybe corsica on wet ground. 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.) on dead stems of 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 broadleaved 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.), from dead culms of Juncus effusus, Cylindromonium everniae and Rhodoveronaea everniae from Evernia prunastri, Cyphellophora sambuci and Myrmecridium sambuci from Sambucus nigra, Kiflimonium junci, Sarocladium 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.) from leaves of 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 a biofilm covering a deteriorated 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 on litter in a mixed forest, Papiliotrema horticola from Malus communis, Paramacroventuria ribis (incl. Paramacroventuria gen. nov.) from leaves 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 on corticated wood. UK, Parasitella quercicola from Quercus robur. USA, Aspergillus arizonicus from indoor air in a hospital, Caeliomyces tampanus (incl. Caeliomyces gen. nov.) from office dust, Cippumomyces mortalis (incl. Cippumomyces gen. nov.) from a tombstone, 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 air in men's locker room and 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 forests and Phytophthora docyniae from soil and roots of Docynia indica. Morphological and culture characteristics are supported by DNA barcodes. Citation: Crous PW, Osieck ER, Jurjevic Z, et al. 2021. Fungal Planet description sheets: 1284-1382. Persoonia 47: 178-374. https://doi.org/10.3767/persoonia.2021.47.06.

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 from a grassland. Croatia, Mollisia inferiseptata from a rotten Laurus nobilis trunk. Cyprus, Amanita exilis on calcareous soil. Czech Republic, Cytospora hippophaicola from wood of symptomatic Vaccinium corymbosum. Denmark, Lasiosphaeria deviata on pieces of wood and herbaceous debris. Dominican Republic, Calocybella goethei among grass on a lawn. France (Corsica), Inocybe corsica on wet ground. 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.) on dead stems of 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 broadleaved 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.), from dead culms of Juncus effusus, Cylindromonium everniae and Rhodoveronaea everniae from Evernia prunastri, Cyphellophora sambuci and Myrmecridium sambuci from Sambucus nigra, Kiflimonium junci, Sarocladium 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.) from leaves of 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 a biofilm covering a deteriorated 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 on litter in a mixed forest, Papiliotrema horticola from Malus communis, Paramacroventuria ribis (incl. Paramacroventuria gen. nov.) from leaves 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 on corticated wood. UK, Parasitella quercicola from Quercus robur. USA, Aspergillus arizonicus from indoor air in a hospital, Caeliomyces tampanus (incl. Caeliomyces gen. nov.) from office dust, Cippumomyces mortalis (incl. Cippumomyces gen. nov.) from a tombstone, 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 air in men's locker room and 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 forests and Phytophthora docyniae from soil and roots of Docynia indica. Morphological and culture characteristics are supported by DNA barcodes. Citation: Crous PW, Osieck ER, Jurjevic Z, et al. 2021. Fungal Planet description sheets: 1284-1382. Persoonia 47: 178-374. https://doi.org/10.3767/persoonia.2021.47.06.

Quality assessment of estrogen receptor and progesterone receptor testing in breast cancer using a tissue microarray-based approach.

Assessing hormone receptor status is an essential part of the breast cancer diagnosis, as this biomarker greatly predicts response to hormonal treatment strategies. As such, hormone receptor testing laboratories are strongly encouraged to participate in external quality control schemes to achieve optimization of their immunohistochemical assays. Nine Dutch pathology departments provided tissue blocks containing invasive breast cancers which were all previously tested for estrogen receptor and/or progesterone receptor expression during routine practice. From these tissue blocks, tissue microarrays were constructed and tested for hormone receptor expression. When a discordant result was found between the local and TMA result, the original testing slide was revised and staining was repeated on a whole-tissue block. Sensitivity and specificity of individual laboratories for testing estrogen receptor expression were high, with an overall sensitivity and specificity [corrected] of 99.7 and 95.4%, respectively. Overall sensitivity and specificity of progesterone receptor testing were 94.8 and 92.6%, respectively. Out of 96 discordant cases, 36 cases would have been concordant if the recommended cut-off value of 1% instead of 10% was followed. Overall sensitivity and specificity of estrogen and progesterone receptor testing were high among participating laboratories. Continued enrollment of laboratories into quality control schemes is essential for achieving and maintaining the highest standard of care for breast cancer patients.

Human epidermal growth factor receptor 2 overexpression and amplification in endoscopic biopsies and resection specimens in esophageal and junctional adenocarcinoma.

Human epidermal growth factor receptor 2 (HER2) is overexpressed in a subset of esophageal adenocarcinomas. Frequently, biopsy material is used for evaluation of HER2 status. The aim of the study was to determine if HER2 expression in preoperative endoscopic biopsies is representative for the entire tumor. Preoperative endoscopic biopsies and matched resection specimens were collected from 75 patients who underwent esophagectomy for esophageal adenocarcinoma. Immunohistochemical staining (IHC) on HER2 and dual-color in situ hybridization (ISH) were performed. HER2 status was determined by following a clinical algorithm, first determining HER2 overexpression on immunohistochemistry and, when equivocal (2+), determining HER2 amplification on ISH. Seventy-one of 75 (95%) biopsies and 69/75 (92%) resection specimens could be analyzed due to technical failure. HER2 positivity was seen in 18/71 (25%) biopsies and in 15/69 (22%) resection specimens. Overall, HER2 status in the biopsy was concordant with HER2 status in the resection specimen in 94% of cases. Interobserver agreement on IHC scoring for all three observers was 83% in biopsies and 85% in resection specimens. HER2 positivity was detected in 22% of esophageal adenocarcinomas. Although interobserver agreement was moderate, HER2 status of a primary tumor can be reliably determined based on the endoscopically obtained pretreatment biopsy.

Predicting non-adherence in patients with familial hypercholesterolemia.

PURPOSE: Familial hypercholesterolemia (FH) is an autosomal dominant disorder associated with a high risk of premature coronary heart disease (CHD). CHD prevention consists of lifestyle changes combined with lifelong statin treatment. Good adherence to statins reduces the risk of events substantially. This study was designed to identify determinants of non-adherence and to develop a model predicting non-adherence. METHODS: A single centre survey included all consecutive heterozygous FH patients above age 18 years, who were treated by a specialized team in the outpatient clinic of a university hospital in The Netherlands between 2008 and 2009. In addition to clinical data, patients completed a questionnaire concerning medication adherence. RESULTS: We analyzed 321 patients (169 women) with a statin prescription whose mean age was 46 ± 14 years (± S.D.), and 13 % of the patients had CHD. The untreated mean total cholesterol was 10 ± 2.3 mmol/l. On average, patients were ten years on cholesterol-lowering therapy (range 1-29 years). Adherence was reported by 89 % of the patients (> 90 % adherence). Non-adherence was associated with younger age (OR = 10.64, 95 % CI 2.86-39.68), high total cholesterol level during prescription (OR = 4.29, 95 % CI 1.86-9.89) and a relatively low untreated total cholesterol level (OR = 3.94 95 % CI 1.39-11.14). A prediction model based on these three determinants had a c-index of 0.78 and a calibration with P = 0.88. CONCLUSION: Based on three independent determinants, a prediction model is developed to identify non-adherent FH patients. This model needs to be tested in future prospective research. It might be a first step in improving statin adherence in this extremely high risk group.

Discordance in ERα, PR and HER2 receptor status across different distant breast cancer metastases within the same patient.

BACKGROUND: We studied discordance in estrogen receptor alpha (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status between multiple distant metastases from the same breast cancer patient. MATERIAL AND METHODS: Multiple distant metastases from 55 female patients were stained for ERα, PR and HER2 by immunohistochemistry and in situ hybridization for confirmation of the HER2 status. RESULTS: Different metastatic sites within the same patient showed discordance in ERα receptor status in 7.3% or 10.9% of patients (using a 10% or 1% threshold for positivity, respectively). For PR, 29.1% or 30.9% of patients showed discordance. Taking ERα and PR together, 36.4% of cases (both thresholds) showed discrepancy between metastases. In 10.9% (10% threshold) or 14.5% of patients (1% threshold), such discordance could have clinical consequences with regard to hormonal treatment. For HER2, there was 3.6% discordance on the immunohistochemical level but 0% on the gene level. CONCLUSION: In a significant proportion of metastatic breast cancer patients, discordance in ERα and PR receptor status between different metastatic sites was observed. This implies that multiple metastases may need to be biopsied to optimally reassess receptors.

New and Interesting Fungi. 6.

Three new genera, six new species, three combinations, six epitypes, and 25 interesting new host and / or geographical records are introduced in this study. New genera: Neoleptodontidium (based on Neoleptodontidium aquaticum), and Nothoramularia (based on Nothoramularia ragnhildianicola). New species: Acremonium aquaticum (from cooling pad water, USA, Cladophialophora laricicola (on dead wood of Larix sp., Netherlands), Cyphellophora neerlandica (on lichen on brick wall, Netherlands), Geonectria muralis (on moss growing on a wall, Netherlands), Harposporium illinoisense (from rockwool, USA), and Neoleptodontidium aquaticum (from hydroponic water, USA). New combinations: Cyphellophora deltoidea (based on Anthopsis deltoidea), Neoleptodontidium aciculare (based on Leptodontidium aciculare), and Nothoramularia ragnhildianicola (based on Ramularia ragnhildianicola). Epitypes: Cephaliophora tropica (from water, USA), Miricatena prunicola (on leaves of Prunus serotina, Netherlands), Nothoramularia ragnhildianicola (on Ragnhildiana ferruginea, parasitic on Artemisia vulgaris, Germany), Phyllosticta multicorniculata (on needles of Abietis balsamea, Canada), Thyronectria caraganae (on twigs of Caragana arborescens, Ukraine), and Trichosphaeria pilosa (on decayed Salix branch, Netherlands). Furthermore, the higher order phylogeny of three genera regarded as incertae sedis is resolved, namely Cephaliophora (Ascodesmidaceae, Pezizales), Miricatena (Helotiales, Leotiomycetes), and Trichosphaeria (Trichosphaeriaceae, Trichosphaeriales), with Trichosphaeriaceae being an older name for Plectosphaerellaceae. Citation: Crous PW, Akulov A, Balashov S, Boers J, Braun U, Castillo J, Delgado MA, Denman S, Erhard A, Gusella G, Jurjevic Z, Kruse J, Malloch DW, Osieck ER, Polizzi G, Schumacher RK, Slootweg E, Starink-Willemse M, van Iperen AL, Verkley GJM, Groenewald JZ (2023). New and Interesting Fungi. 6. Fungal Systematics and Evolution 11: 109-156. doi: 10.3114/fuse.2023.11.09.

Genetic and epigenetic determinants of reactivation of Mecp2 and the inactive X chromosome in neural stem cells.

Rett syndrome may be treated by reactivating the silent copy of Mecp2 from the inactive X chromosome in female cells. Most studies that model Mecp2 reactivation have used mouse fibroblasts rather than neural cells, which would be critical for phenotypic reversal, and rely on fluorescent reporters that lack adequate sensitivity. Here, we present a mouse model based on a dual bioluminescent and fluorescent reporter to assess the level of reactivation of Mecp2 and the inactive X chromosome by treating neural stem cells with 5-azacytidine and Xist knockdown. We show that reactivation of Mecp2 and other X-linked genes correlates with CpG density, with distance from escapees, and, very strongly, with the presence of short interspersed nuclear elements. In addition, X-linked genes reactivated in neural stem cells overlap substantially with early reactivating genes by induced pluripotent stem cell reprogramming of fibroblasts or neuronal progenitors, indicating that X chromosome reactivation follows similar paths regardless of the technique or cell type used.

New and Interesting Fungi. 5.

Nine new genera, 17 new species, nine new combinations, seven epitypes, three lectotypes, one neotype, and 14 interesting new host and / or geographical records are introduced in this study. New genera: Neobarrmaelia (based on Neobarrmaelia hyphaenes), Neobryochiton (based on Neobryochiton narthecii), Neocamarographium (based on Neocamarographium carpini), Nothocladosporium (based on Nothocladosporium syzygii), Nothopseudocercospora (based on Nothopseudocercospora dictamni), Paracamarographium (based on Paracamarographium koreanum), Pseudohormonema (based on Pseudohormonema sordidus), Quasiphoma (based on Quasiphoma hyphaenes), Rapidomyces (based on Rapidomyces narthecii). New species: Ascocorticium sorbicola (on leaves of Sorbus aucuparia, Belgium), Dactylaria retrophylli (on leaves of Retrophyllum rospigliosii, Colombia), Dactylellina miltoniae (on twigs of Miltonia clowesii, Colombia), Exophiala eucalyptigena (on dead leaves of Eucalyptus viminalis subsp. viminalis supporting Idolothrips spectrum, Australia), Idriellomyces syzygii (on leaves of Syzygium chordatum, South Africa), Microcera lichenicola (on Parmelia sulcata, Netherlands), Neobarrmaelia hyphaenes (on leaves of Hyphaene sp., South Africa), Neobryochiton narthecii (on dead leaves of Narthecium ossifragum, Netherlands), Niesslia pseudoexilis (on dead leaf of Quercus petraea, Serbia), Nothocladosporium syzygii (on leaves of Syzygium chordatum, South Africa), Nothotrimmatostroma corymbiae (on leaves of Corymbia henryi, South Africa), Phaeosphaeria hyphaenes (on leaves of Hyphaene sp., South Africa), Pseudohormonema sordidus (on a from human pacemaker, USA), Quasiphoma hyphaenes (on leaves of Hyphaene sp., South Africa), Rapidomyces narthecii (on dead leaves of Narthecium ossifragum, Netherlands), Reticulascus parahennebertii (on dead culm of Juncus inflexus, Netherlands), Scytalidium philadelphianum (from compressed air in a factory, USA). New combinations: Neobarrmaelia serenoae, Nothopseudocercospora dictamni, Dothiora viticola, Floricola sulcata, Neocamarographium carpini, Paracamarographium koreanum, Rhexocercosporidium bellocense, Russula lilacina. Epitypes: Elsinoe corni (on leaves of Cornus florida, USA), Leptopeltis litigiosa (on dead leaf fronds of Pteridium aquilinum, Netherlands), Nothopseudocercospora dictamni (on living leaves of Dictamnus albus, Russia), Ramularia arvensis (on leaves of Potentilla reptans, Netherlands), Rhexocercosporidium bellocense (on leaves of Verbascum sp., Germany), Rhopographus filicinus (on dead leaf fronds of Pteridium aquilinum, Netherlands), Septoria robiniae (on leaves of Robinia pseudoacacia, Belgium). Lectotypes: Leptopeltis litigiosa (on Pteridium aquilinum, France), Rhopographus filicinus (on dead leaf fronds of Pteridium aquilinum, Netherlands), Septoria robiniae (on leaves of Robinia pseudoacacia, Belgium). Neotype: Camarographium stephensii (on dead leaf fronds of Pteridium aquilinum, Netherlands). Citation: Crous PW, Begoude BAD, Boers J, Braun U, Declercq B, Dijksterhuis J, Elliott TF, Garay-Rodriguez GA, Jurjevic Z, Kruse J, Linde CC, Loyd A, Mound L, Osieck ER, Rivera-Vargas LI, Quimbita AM, Rodas CA, Roux J, Schumacher RK, Starink-Willemse M, Thangavel R, Trappe JM, van Iperen AL, Van Steenwinkel C, Wells A, Wingfield MJ, Yilmaz N, Groenewald JZ (2022) New and Interesting Fungi. 5. Fungal Systematics and Evolution 10: 19-90. doi: 10.3114/fuse.2022.10.02.

An aid to the diagnosis of genetic disorders underlying adult-onset renal failure: a literature review.

Several genetic disorders can present in adult patients with renal insufficiency. Genetic renal disease other than ADPKD accounts for ESRD in 3% of the adult Dutch population. Because of this low prevalence and their clinical heterogeneity most adult nephrologists are less familiar with these disorders. As a guideline to differential diagnosis, we provide an overview of the clinical manifestations and the pathogenesis of the main genetic disorders with chronic renal insufficiency surfacing in adulthood and add an algorithm plus 4 tables. We also indicate where molecular genetics nowadays can be of aid in the diagnostic process. The following disorders are discussed by mode of inheritance: 1) Autosomal dominant: autosomal dominant polycystic kidney disease, nephropathies associated with uromodulin (medullary cystic disease and familial juvenile hyperuricemic nephropathy), renal cysts and diabetes syndrome, nail-patella syndrome, glomerulopathy with fibronectin deposits. 2) Not autosomal dominant: Nephronophthisis, Fabry disease, primary oxalosis, Adenine Phosphoribosyl Transferase deficiency, Alport syndrome, Lecithin-cholesterol acyltransferase deficiency, adult-onset cystinosis.

No effect of PCSK9 inhibitors on D-dimer and fibrinogen levels in patients with familial hypercholesterolemia.

Statins are generally believed to have cardiovascular protective effects independent of low-density lipoprotein-cholesterol (LDL-C) lowering, such as antithrombotic effects characterized by a decrease in D-dimer levels. For the recently introduced Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors antithrombotic effects are yet unknown. We determined the effect of starting PCSK9 inhibitors on D-dimer and fibrinogen levels as most robust markers for thrombogenicity in statin-intolerant patients with familial hypercholesterolemia. We determined D-dimer and fibrinogen levels before and after start of evolocumab (n = 19) or alirocumab (n = 11). Baseline median D-dimer levels were 0.34 mg/L (IQR 0.24-0.59 mg/L) and baseline median fibrinogen levels 3.2 g/L (IQR 2.88-3.63 g/L). At follow-up D-dimer levels (median 0.31 mg/L (IQR 0.25-0.59 mg/L); p = 0.37), and fibrinogen levels (median 3.4 g/L (IQR 2.98-3.62 g/L); p = 0.38) did not change significantly. We therefore conclude PCSK9 inhibitors do not seem to have a profound antithrombotic effect, although a more subtle effect can not been excluded.

Ultrastructural evidence for direct excitatory retroambiguus projections to cutaneous trunci and abdominal external oblique muscle motoneurons in the cat.

The nucleus retroambiguus (NRA) is a group of neurons, located laterally in the caudal medulla oblongata. The NRA is thought to modulate abdominal pressure in the framework of respiration, vomiting, vocalization, probably parturition, and, in all likelihood mating behavior. The NRA exerts this control through its projections to motoneurons to the nucleus ambiguus in the lateral medulla (innervating pharynx, larynx), and spinal cord (innervating cutaneous trunci, intercostal, abdominal, pelvic floor, and lower limb muscles). The nature of these NRA-motoneuronal projections is unknown. In this study we have determined the ultrastructure of the NRA-motoneuronal projections, and especially those to the abdominal external oblique and cutaneous trunci muscles. In four cats 0.1% cholera toxin subunit b was injected in the external oblique and cutaneous trunci muscles to retrogradely label their motoneurons in the spinal cord. Wheat germ agglutinin-conjugated horseradish peroxidase was injected into the NRA to anterogradely label its contralaterally descending fibers to the motoneurons of both muscles. In order to prevent anterograde labeling of ipsilaterally descending systems not originating from the NRA, a hemisection was made at the level of C2 prior to the NRA injection. The ultrastructural results indicate that the majority (60-74%) of the anterogradely labeled NRA-terminals made monosynaptic contacts with retrogradely labeled dendrites of the external oblique and the cutaneous trunci muscle motoneurons. The majority (86-95%) of the NRA terminals made asymmetric synaptic contacts and 79-84% contained round vesicles. These results demonstrate the existence of direct, presumably excitatory, projections from NRA to external oblique and cutaneous trunci muscle motoneurons.

[Weight loss, serum sodium concentration and residual symptoms in patients with hypernatremic dehydration caused by insufficient breastfeeding]. / Gewichtsverlies, serumnatriumconcentratie en restverschijnselen bij patiëntjes met hypertone dehydratie door onvoldoende borstvoeding.

OBJECTIVE: To determine the relationship between serum sodium concentration and weight loss as well as residual symptoms in newborns with hypernatremic dehydration caused by insufficient breastfeeding; and to determine the sensitivity of the following rule of thumb 'if weight loss is less than 10%, the baby does not have hypernatremic dehydration caused by insufficient breastfeeding'. DESIGN: Systematic literature search. METHOD: Medline was searched using the terms 'dehydration AND breastfeeding' for case reports on patients with 'hypernatremic dehydration caused by insufficient breastfeeding'. Reference lists from the articles retrieved were also searched. Articles published in 1970-2004 in Dutch, English, French, and German were included. All cases that the author diagnosed as 'hypernatremic dehydration caused by insufficient breastfeeding' were included. RESULTS: A total of 47 articles were found, containing 128 relevant cases. Of these, 9 had less than 10% weight loss. Therefore, the sensitivity of the 10% rule was 93%. We found a linear relationship between the degree of weight loss and serum sodium concentration (Pearson's correlation coefficient = 0.71; p < 0.001). For every 10% increase in weight loss, the serum sodium concentration increased by 16 mmol/l (95% CI: 13-19). As the serum sodium concentration increased, the prevalence of residual symptoms increased. No residual symptoms were reported in patients with less than 10% weight loss. CONCLUSION: A relatively strong linear relationship was found between weight loss and serum sodium concentration. If the weight loss was more than 10%, the serum sodium concentration was beyond the range of normal values. The rule of thumb had a high sensitivity; however, the specificity should be determined before the rule of thumb is implemented.

In cat four times as many lamina I neurons project to the parabrachial nuclei and twice as many to the periaqueductal gray as to the thalamus.

The spinothalamic tract, and especially its fibers originating in lamina I, is the best known pathway for transmission of nociceptive information. On the other hand, different studies have suggested that more lamina I cells project to the parabrachial nuclei (PBN) and periaqueductal gray (PAG) than to the thalamus. The exact ratio of the number of lamina I projections to PBN, PAG and thalamus is not known, because comprehensive studies examining these three projections from all spinal segments, using the same tracers and counting methods, do not exist. In the present study, the differences in number and distribution of retrogradely labeled lamina I cells in each segment of the cat spinal cord (C1-Coc2) were determined after large wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) injections in either PBN, PAG or thalamus. We estimate that approximately 6000 lamina I cells project to PBN, 3000 to PAG and less than 1500 to the thalamus. Of the lamina I cells projecting to thalamus or PAG more than 80%, and of the lamina I-PBN cells approximately 60%, were located on the contralateral side. In all cases, most labeled lamina I cells were found in the upper two cervical segments and in the cervical and lumbar enlargements.

Dyslipidemia testing: Why, for whom and when.

Dyslipidemia is a major risk factor for cardiovascular disease. This review addresses why, who and when to test for dyslipidemia. The essence why to test lipids is that those individuals recognized to potentially benefit from primary cardiovascular risk prevention, have a complete cardiovascular risk assessment. Who and when to test lipids differs among the major European, English and American guidelines regarding the recommended age and approach. It is important to note that the threshold and the frequency in whom to perform risk assessment is not established. Most important in decisions concerning lipid testing is communication and to involve individual circumstances.

Cascade screening of familial hypercholesterolemia must go on.

PURPOSE: This study assesses the success of the recently terminated Dutch nationwide cascade screening by examining whether children with familial hypercholesterolemia (FH) were identified through family screening or due to cardiovascular (CVD) events in the FH parent. METHODS: We collected clinical information of all children (0-18 years) with FH with a pathogenic variant at our outpatient lipid clinic between 1992 and 2014 and their FH parents and FH grandparents. RESULTS: We analysed 292 FH children from 205 parents with FH. A history of premature CVD was present in 20% of the parents (29% of the fathers, 9% of the mothers) and 49% of the FH grandparents. CONCLUSION: The fact that CVD is still a presenting event of FH in especially fathers shows that nationwide screening might have been terminated too early. Therefore we recommend to proceed the cascade screening.

Neuroendocrine-specific protein C (NSP-C): subcellular localization and differential expression in relation to NSP-A.

A mouse monoclonal antibody RNL-4, as well as rabbit polyclonal antiserum POL-8 were raised against a synthetic peptide, encompassing the first twenty unique amino-terminal amino acid residues of NSP-C. The specificity of both immunoreagents was established in an ELISA assay using the synthetic peptide and by their immunoreactivity to NSP-C fusion proteins. Immunofluorescence analysis of COS-1 cells, transfected with NSP-C cDNA, showed staining of the endoplasmic reticulum with RNL-4 and POL-8. No cross-reactivity of these reagents with NSP-A or NSP-B was seen. Immunohistochemical studies in normal human tissues showed expression of NSP-C in tissues of neural and neuroendocrine origin, i.e. neurons of the central and peripheral nervous system, the neurohypophysis, adrenal medulla, adenohypophysis, pars intermedia, and in sporadic neuroedocrine cells of the lung. Expression of NSP-C was found in several small cell lung cancer (SCLC) cell lines, in non-SCLC cell lines with neuroendocrine features, but not in typical non-SCLC cell lines. Also, in a neuroblastoma cell line NSP-C expression was observed. Immunoblotting and immunoprecipitation studies with RNL-4 and POL-8 identified the 23 kDa NSP-C polypeptide in these cell lines. Immunofluorescence microscopy showed that also in these cell lines NSP-C is located at the endoplasmic reticulum, as shown before for NSP-A and NSP-B. In some of the cell lines coexpression of NSP-A and NSP-C was observed, while in others only one of the two could be detected. The differential expression of NSP-A and NSP-C in these cell lines is confirmed by immunoblotting and was also evident at the mRNA level. When NSP-A and NSP-C were coexpressed, the number of NSP-C-positive cells was always less than the number of NSP-A-positive cells. A partial colocalization of NSPs was observed in the endoplasmic reticulum. Cell fractionation studies revealed that both proteins are retained in the membranous fraction of the cell, from which they can be solubilized by Triton X-100. Immunoprecipitation analyses under native conditions indicate that NSP-C does not need to associate with NSP-A to form high molecular weight NSP-reticulons.

Genetic localization of Bethlem myopathy.

Bethlem myopathy is a rare autosomal dominant myopathy characterized by slowly progressive limb-girdle muscular atrophy and weakness, and contractures of multiple joints. To identify the genetic localization we used highly polymorphic microsatellite markers in a genome-wide search in six Dutch families. After excluding genetic linkage with 52 markers distributed evenly over the autosomes, significant linkage was present with the 21q22.3 locus PFKL (two-point lod score of Zmax = 6.86 at theta = 0.03). There was no indication of genetic heterogeneity. The pattern of recombinations observed with adjacent markers indicated a localization distal to PFKL. Recombination of a marker within the collagen 6a1 gene (COL6A1) excluded this apparent candidate gene in one of the Bethlem myopathy families. The disease gene is most likely located in the region between COL6A1 and the telomere of chromosome 21q.