Re-examination of the Southern Hemisphere truffle genus Amylascus (Pezizaceae, Ascomycota) and characterization of the sister genus Nothoamylascus gen. nov.

Amylascus is a genus of ectomycorrhizal truffles within Pezizaceae that is known from Australia and contains only two described species, A. herbertianus and A. tasmanicus. Species of Amylascus are closely related to truffles (Pachyphlodes, Luteoamylascus) and cup fungi (Plicariella) from the Northern Hemisphere. Here we reevaluate the species diversity of Amylascus and related taxa from southern South America and Australia based on new morphological and molecular data. We identify previously undocumented diversity and morphological variability in ascospore color, ascospore ornamentation, hymenial construction, epithecium structure and the amyloid reaction of the ascus in Melzer's reagent. We redescribe two Amylascus species from Australia and describe seven new Amylascus species, five from South America and two from Australia. This is the first report of Amylascus species from South America. We also describe the new South American genus Nothoamylascus as sister lineage to the Pachyphlodes-Amylascus-Luteoamylascus clade (including Amylascus, Luteoamylascus, Pachyphlodes, and Plicariella). We obtained ITS sequences of mitotic spore mats from Nothoamylascus erubescens gen. & sp. nov. and four of the seven newly described Amylascus species, providing the first evidence of mitotic spore mats in Amylascus. Additional ITS sequences from mitotic spore mats reveal the presence of nine additional undescribed Amylascus and one Nothoamylascus species that do not correspond to any sampled ascomata. We also identify three additional undescribed Amylascus species based on environmental sequences from the feces of two grounddwelling bird species from Chile, Scelorchilus rubecula and Pteroptochos tarnii. Our results indicate that ascomata from Amylascus and Nothoamylascus species are rarely collected, but molecular data from ectomycorrhizal roots and mitotic spore mats indicate that these species are probably common and widespread in southern South America. Finally, we present a time-calibrated phylogeny that is consistent with a late Gondwanan distribution. The time since the most recent common ancestor of: 1) the family Pezizaceae had a mean of 276 Ma (217-337 HPD); 2) the Amylascus-Pachyphlodes-Nothoamylascus-Luteoamylascus clade had a mean of 79 Ma (60-100 HPD); and 3) the Amylascus-Pachyphlodes clade had a mean of 50 Ma (38-62 HPD). The crown age of Pachyphlodes had a mean of 39 Ma (25-42 HPD) and Amylascus had a mean age of 28 Ma (20-37 HPD), falling near the Eocene-Oligocene boundary and the onset of the Antarctic glaciation (c. 35 Ma). Citation: Healy RA, Truong C, Castellano MA, et al. 2023. Re-examination of the Southern Hemisphere truffle genus Amylascus (Pezizaceae, Ascomycota) and characterization of the sister genus Nothoamylascus gen. nov. Persoonia 51: 125-151. doi: 10.3767/persoonia.2023.51.03.

Precipitation of greigite and pyrite induced by Thermococcales: an advantage to live in Fe- and S-rich environments?

Thermococcales, a major order of archaea inhabiting the iron- and sulfur-rich anaerobic parts of hydrothermal deep-sea vents, have been shown to rapidly produce abundant quantities of pyrite FeS2 in iron-sulfur-rich fluids at 85°C, suggesting that they may contribute to the formation of 'low temperature' FeS2 in their ecosystem. We show that this process operates in Thermococcus kodakarensis only when zero-valent sulfur is directly available as intracellular sulfur vesicles. Whether in the presence or absence of zero-valent sulfur, significant amounts of Fe3 S4 greigite nanocrystals are formed extracellularly. We also show that mineralization of iron sulfides induces massive cell mortality but that concomitantly with the formation of greigite and/or pyrite, a new generation of cells can grow. This phenomenon is observed for Fe concentrations of 5 mM but not higher suggesting that above a threshold in the iron pulse all cells are lysed. We hypothesize that iron sulfides precipitation on former cell materials might induce the release of nutrients in the mineralization medium further used by a fraction of surviving non-mineralized cells allowing production of new alive cells. This suggests that biologically induced mineralization of iron-sulfides could be part of a survival strategy employed by Thermococcales to cope with mineralizing high-temperature hydrothermal environments.

Resurrecting the genus Geomorium: Systematic study of fungi in the genera Underwoodia and Gymnohydnotrya (Pezizales) with the description of three new South American species.

Molecular phylogenetic analyses have addressed the systematic position of several major Northern Hemisphere lineages of Pezizales but the taxa of the Southern Hemisphere remain understudied. This study focuses on the molecular systematics and taxonomy of Southern Hemisphere species currently treated in the genera Underwoodia and Gymnohydnotrya. Species in these genera have been identified as the monophyletic /gymnohydnotrya lineage, but no further research has been conducted to determine the evolutionary origin of this lineage or its relationship with other Pezizales lineages. Here, we present a phylogenetic study of fungal species previously described in Underwoodia and Gymnohydnotrya, with sampling of all but one described species. We revise the taxonomy of this lineage and describe three new species from the Patagonian region of South America. Our results show that none of these Southern Hemisphere species are closely related to Underwoodia columnaris, the type species of the genus Underwoodia. Accordingly, we recognize the genus Geomorium described by Spegazzini in 1922 for G. fuegianum. We propose the new family, Geomoriaceae fam. nov., to accommodate this phylogenetically and morphologically unique Southern Hemisphere lineage. Molecular dating estimated that Geomoriaceae started to diverge from its sister clade Tuberaceae c. 112 MYA, with a crown age for the family in the late Cretaceous (c. 67 MYA). This scenario fits well with a Gondwanan origin of the family before the split of Australia and South America from Antarctica during the Paleocene-Eocene boundary (c. 50 MYA).

Mammalian mycophagy: A global review of ecosystem interactions between mammals and fungi.

The consumption of fungi by animals is a significant trophic interaction in most terrestrial ecosystems, yet the role mammals play in these associations has been incompletely studied. In this review, we compile 1 154 references published over the last 146 years and provide the first comprehensive global review of mammal species known to eat fungi (508 species in 15 orders). We review experimental studies that found viable fungal inoculum in the scats of at least 40 mammal species, including spores from at least 58 mycorrhizal fungal species that remained viable after ingestion by mammals. We provide a summary of mammal behaviours relating to the consumption of fungi, the nutritional importance of fungi for mammals, and the role of mammals in fungal spore dispersal. We also provide evidence to suggest that the morphological evolution of sequestrate fungal sporocarps (fruiting bodies) has likely been driven in part by the dispersal advantages provided by mammals. Finally, we demonstrate how these interconnected associations are widespread globally and have far-reaching ecological implications for mammals, fungi and associated plants in most terrestrial ecosystems. Citation: Elliott TF, Truong C, Jackson S, Zúñiga CL, Trappe JM, Vernes K (2022). Mammalian mycophagy: a global review of ecosystem interactions between mammals and fungi. Fungal Systematics and Evolution 9: 99-159. doi: 10.3114/fuse.2022.09.07.

The role of self-disclosure by peer mentors: Using personal narratives in depression care.

OBJECTIVE: Self-disclosure is recognized as an important aspect of peer support, but little is known about its use by peers. This study aimed to qualitatively understand peer self-disclosure in the context of depression care delivery to older adults. METHODS: 69 audio-recordings of peer-client meetings were coded for self-disclosure using the Roter Interaction Analysis System (RIAS). Peer self-disclosure was defined as a statement describing personal life experience with physical and/or emotional relevance for the client. A total of 3421 discrete statements were organized into 770 disclosure episodes. The episodes were qualitatively analyzed to identify themes related to the content and function of self-disclosure within the peer-counseling context. RESULTS: Peer self-disclosure was used to 1) counsel through reframing perspectives, modeling positive behaviors, offering coping skills, and sharing mental health resources and health information; 2) establish rapport by emphasizing similarities unrelated to depression; and 3) show empathy and understanding of personal struggles. In addition, self-disclosure rarely only focused on the peer experience without relevance for the client. CONCLUSIONS & PRACTICE IMPLICATIONS: Peer self-disclosure can be purposively used in depression care delivery with older adults. Training and supervision in appropriate self-disclosure should be provided to peers to ensure purposive use.

Challenges on the road to recovery: Exploring attitudes and experiences of clients in a community-based buprenorphine program in Baltimore City.

OBJECTIVE: This qualitative study identifies and describes experiences and challenges to retention of individuals with opioid use disorder (OUD) who participated in a low-threshold combined buprenorphine-peer support treatment program in Baltimore. METHODS: In-depth semi-structured interviews with staff and former clients of the Project Connections Buprenorphine Program (PCBP) (9 people) and focus group discussions with current and previous clients of PCBP (7 people) were conducted. Content analysis was used to extract themes regarding barriers to enrolling and remaining in, and transitioning from the program. RESULTS: Primary challenges identified by the participants included struggles with cravings and symptoms of withdrawal, comorbid mental health issues, criminal justice system involvement, medication stigma, and conflicts over level of flexibility regarding program requirements and the role of employment. CONCLUSIONS: This study identified several obstacles clients face when seeking care through a combined buprenorphine-peer support model. Findings highlight potential programmatic factors that can be improved and additional resources that may support treatment retention rates and better outcomes. Despite challenges, low-threshold and community-based programs can increase access to effective maintenance treatment for OUD, especially among vulnerable populations who may not have access to formal health services.

Clinical and molecular features of mitochondrial DNA depletion due to mutations in deoxyguanosine kinase.

Published mutations in deoxyguanosine kinase (DGUOK) cause mitochondrial DNA depletion and a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia. In this series, we have identified 15 different mutations in the DGUOK gene from 9 kindreds. Among them, 12 have not previously been reported. Nonsense, splice site, or frame-shift mutations that produce truncated proteins predominate over missense mutations. All patients who harbor null mutations had early onset liver failure and significant neurological disease. These patients have all died before 2-years of age. Conversely, two patients carrying missense mutations had isolated liver disease and are alive in their 4th year of life without liver transplant. Five subjects were detected by newborn screening, with elevated tyrosine or phenylalanine. Consequently, this disease should be considered if elevated tyrosine is identified by newborn screening. Mitochondrial DNA content was below 10% of controls in liver in all but one case and modestly reduced in blood cells. With this paper a total of 39 different mutations in DGUOK have been identified. The most frequent mutation, c.763_c.766dupGATT, occurs in 8 unrelated kindreds. 70% of mutations occur in only one kindred, suggesting full sequencing of this gene is required for diagnosis. The presentation of one case with apparent viral hepatitis, without neurological disease, suggests that this disease should be considered in patients with infantile liver failure regardless of the presence of neurological features or apparent infectious etiology.

Metabolism and function of platelet-activating factor in fetal rabbit lung development.

Previously, platelet-activating factor (PAF, PAF-acether, 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) had been identified in association with a lamellar-body-enriched fraction of human amniotic fluid obtained from women in labor. In consideration of the fact that fetal lung is the source of lamellar bodies, we have investigated the capacity of the developing lung to synthesize PAF. The specific activity of the PAF biosynthetic enzyme, 1-alkyl-2-lyso-sn-glycero-3-phosphocholine: acetyl-CoA acetyltransferase, increased from 116 pmol/min per mg protein in day 21 fetal rabbit lung to 332 pmol/min per mg protein by day 31. Although this enzymatic activity in fetal kidney also increased, it never reached the level found in lung. In contrast, the actyltransferase activity decreased by 80% in fetal liver between days 21 and 31. The acetyltransferase activity in lung was primarily localized in the microsomal fraction (105 000 X g pellet); however a significant proportion of the activity was found in the 18 000 X g pellet. The specific activity of acetyltransferase in adult alveolar type II rat pneumonocytes was significantly higher than that of adult rat lung or rat alveolar macrophages, suggesting that type II cells make a significant contribution to the actyltransferase activity of lung tissue. PAF acetylhydrolase remained relatively constant throughout the gestation in all tissues. The concentration of PAF in the fetal lung increased by 3-fold from 12 to 35 fmol/mg protein, between day 21 and day 31 of development. The concentrations of the PAF precursors, 2-lyso-PAF (1-alkyl-2-lyso-sn-glycero-3-phosphocholine) and the 2-acyl derivative, were several orders of magnitude higher than the PAF concentration. The pulmonary glycogen content decreased from 163 at day 21 to 35 micrograms/mg protein at day 31 of gestation. We suggest that the increase in PAF concentration may participate in the regulation of glycogen breakdown in fetal lung as it does in perfused rat liver (Shukla, S.D., Buxton, D.B., Olson, M.S. and Hanahan, D.J. (1983) J. Biol. Chem. 258, 10212-10214). The formation of PAF in the developing lung and its secretion, in association with lamellar bodies, into amniotic fluid is discussed in relation to parturition.

Assembly and immunogenicity of chimeric Gag-Env proteins derived from the human immunodeficiency virus type 1.

We evaluated the potential of the precursor Gag protein (Pr55) of the human immunodeficiency virus type 1 (HIV-1) as a carrier for the presentation of envelope epitopes. Recombinant chimeric core-envelope protein-expressing constructs were derived by deletion of regions within the gag gene, especially of regions encoding p24 capsid epitopes. Sequences encoding either the principal neutralization determinant (PND) and/or the CD4-binding domains (CD4BS) were then inserted. Deletion of residues 196-226 within the p24 capsid protein did not prevent self-assembly into virus-like particles (VLPs) whereas deletion of residues 299-328 completely abolished VLP formation. Thus the major homology region (MHR) and proximal sequences are required for capsid assembly. An immunization study in mice showed that assembled chimeric proteins elicited strong anti-Gag, weak anti-envelope, and no neutralizing humoral responses. Nonassembled chimeric proteins were poor immunogens. Mapping of Pr55 antigenic sites using sera from immunized mice and peptides overlapping the entire Gag precursor showed that p24 capsid and p17 matrix epitopes presented to the immune system differed from the mature form (p24 or p17) and the multimeric immature form (Pr55).

A simple procedure to generate chimeric Pr55gag virus-like particles expressing the principal neutralization domain of human immunodeficiency virus type 1.

The Pr55gag human immunodeficiency virus type 1 (HIV-1) precursor protein that is capable of auto-assembling was used as a carrier for a consensus sequence of the principal neutralization domain (PND) of the HIV-1 envelope. For this purpose, a modified HIV-1 gag gene with deletion of the sequence encoding a previously described p24 epitope (amino acids 196-228 of Pr55gag) was first obtained using PCR with degenerate primers, and then cloned. This deleted gag gene allowed in a second time the insertion of a synthetic oligonucleotide cassette encoding the North American/European consensus PND precisely in place of the p24 epitope. The chimeric gene was then inserted into a baculovirus transfer vector and expressed in insect cells. The construct formed 100-140 nm virus-like particles that were released into the extracellular medium. The use of a serum-free medium that supports growth of insect cells facilitated the downstream purification of the extracellular particles. The chimeric particles were recognized by monoclonal antibodies directed to V3 by Western blot but not by immune electron microscopy, suggesting that, although the inserted sequence was still antigenic it was not exposed at the surface of the particles. The results show the ability of Pr55gag to serve as a carrier for easy insertion, in a precisely defined region, of selected epitopes of gp120 surface envelope protein, and to still auto-assemble in virus-like particles. However, the data indicate that exposed epitopes of the mature p24 protein are not presented similarly in the Pr55 precursor, and therefore that different constructs with various insertions in different places must be generated. Such constructs offer an attractive approach for HIV vaccine development and will need evaluation for both antigenicity and immunogenicity.

An ORF2 protein-based ELISA for porcine circovirus type 2 antibodies in post-weaning multisystemic wasting syndrome.

Porcine circovirus type 2 (PCV2) plays a crucial role in the pathogenesis of post-weaning multisystemic wasting syndrome (PMWS) in swine. As PCV2 displays significant homology with PCV1 (a non-pathogenic virus) at the nucleotide and amino-acid level, a discriminative antigen is needed for specific serological diagnosis. The ORF2-encoded capsid protein from PCV2 was used to develop an indirect enzyme-linked immunosorbent assay (ELISA). GST-fused capsid protein from PCV2 and GST alone (both expressed in recombinant baculovirus-infected cells) were used as antigens for serodiagnosis. The specificity of the ELISA for detection of PCV2 antibodies was demonstrated in sera from pigs experimentally infected with PCV1, PCV2 and other swine viruses. The semi-quantitative nature of the test was evaluated versus an immunoperoxidase monolayer assay (IPMA). The ELISA was performed on 322 sera from pigs in eight Brittany herds and compared with IPMA. The sensitivity (98.2%) and specificity (94.5%) of this test were considered suitable for individual serological detection. High PCV2 seroprevalence was found in sows and pigs at the end of the growth phase (18-19 weeks) in all eight herds. The seroprevalence in piglets (11-17 weeks) was statistically correlated with clinical symptoms of PMWS (93% in affected versus 54%, in non-affected farms). A cohort study performed in PMWS-free farms showed that 57% of piglets exhibited active seroconversion after 13 weeks, indicating that PCV2 infection occurred earlier in PMWS-affected piglets.

An experimental model for post-weaning multisystemic wasting syndrome (PMWS) in growing piglets.

Post-weaning multisystemic wasting syndrome (PMWS) is a comparatively new disease of swine, and known to occur in France since 1996. A porcine circovirus type 2 (PCV2) is found in the lesions of affected piglets. Six piglets aged 10-13 weeks were obtained from a French PMWS-affected farm. Two showing characteristic signs of PMWS (palor, weakness and emaciation) remained in poor condition and were finally killed 6 and 9 days after their arrival in the experimental unit. Tissue homogenates from these two piglets were used to reproduce mild PMWS in specific pathogen-free (SPF) piglets. This mild PMWS consisted of pyrexia (up to 41.7 degrees C) and growth retardation (up to 30% of weight reduction compared with controls) commencing 1 week after infection and lasting 3 weeks. In seven additional trials, pyrexia, growth retardation and lesions characteristic of PMWS were consistently produced in SPF and conventional piglets. However, only four of 55 inoculated SPF piglets (7.2%) showed severe wasting disease. One died and the others had to be killed 3 to 4 weeks after inoculation. None of the inoculated animals developed antibodies to any common swine viruses or bacteria, but clear evidence of PCV2 seroconversion was obtained. Our results therefore strongly suggest that PCV2 is the primary aetiological agent of PMWS.

[Seasonal variations of blood pressure in normal subjects and patients with chronic disease]. / Variations saisonnières de la pression artérielle chez des sujets normaux et des malades chroniques.

The characteristics and determining factors of seasonal variations of the blood pressure (BP) were studied in 20 normal subjects and 219 chronic stable chronically all patients, most of whom were ambulatory. The BP was measured repetitively over twelve months and measurements in the lying position repeated after one minute of orthostatism were performed in Winter and in Summer. In normal subjects, the BP decreased from June to reach its lowest value in August to return to the Winter values from October. The mean BP of the three Winter months was 130/79 mmHg and the seasonal lowering averages 5 +/- 5/5 +/- 6 mmHg (m +/- SD) (p < 0.01), with marked individual differences. The Summer decrease in BP was observed both lying down (3/4 mmHg) (p = 0.01) and standing (5/6) (p = 0.0001). In the patient group, the Summer decrease in BP was 4/3 mmHg. During the orthostatic measurements, it was 4/4 mmHg lying down and 6/5 mmHg when upright. Symptoms of orthostatic hypotension were reported spontaneously 10 times during the Winter and 21 times during the Summer months (p = 0.04) and occurred in the upright position in 12 patients (6%) in Winter and 25 patients (12%) in Summer (p = 0.025). The Summer decrease was greater in women than in men. Blood pressure lowering drugs increased this effect and the association of several drugs had an additive effect. It increased with age but disappeared after 70-80 years of age. The very elderly patients on antihypertensive therapy showed a marked decrease in BP during the Summer, especially in the upright position. The Summer decrease in BP is important for the management of elderly patients with hypertension or cardiac failure. It may favorize symptoms of orthostatic hypotension and increase the risk of malaise.

Anesthetic management of a parturient with mixed mitral valve disease and uncontrolled atrial fibrillation.

This case report describes the anesthetic management of a 32-year-old parturient with combined severe mitral regurgitation and moderate mitral stenosis, complicated by fast atrial fibrillation. The advantageous effects of epidural analgesia during labor and vaginal delivery and the importance of invasive monitoring are discussed. We also report the rare complication of right bundle branch block related to the use of a pulmonary artery catheter.

Establishment of drug chests in commune health stations in Vietnam, Bamako Initiative.

In remote areas in Vietnam essential drugs are often not available. Some of the reasons are inadequate resources and failure of distribution. All activities at the health stations are very weak, partly because of inappropriate usage of drugs and lack of fund for buying drugs. The object of the project was to establish sustainable provision of essential drugs for commune health stations in rural areas, to teach the health personnel the importance of essential drugs and to create incentives for the staff and a certain surplus for other health activities. Four District Health Centers (DHC) and 10 Health Stations (HS), 2-4 in each DHC were selected. A pharmacist was made monitor of the project. The health personnel were trained in proper use of drugs, drug prescription, price setting, book keeping and management of pharmacy. Written guidelines were produced. One person was responsible for the drug chest at each HS. After recognizing the aim of the project and signing the contract by which the responsible person was bound, the initial capital was given free. The DHC was responsible for the supervision and advice to the HS. Reporting on prescribed drugs, buying and selling price, profit and fund left took place monthly. Monitoring of recovery of capital, turnover rate, rate of essential drugs and incentives for staff were monitored on forms and quarterly collected by the monitor on his visits. The HS were visited half-yearly by a steering group. All ten HS had been able to establish and maintain the pharmacy and to fully recover or even increase the capital and to create a surplus. Seven out of ten HSs had a turnover rate of more than one. The rate of essential drugs sold was more than 60% in seven pharmacies. The interest rate of 18% on average was used for incentives for staff, to provide drugs for those who cannot pay and for equipment for the HS. The cooperation between the DHC and the HS became closer. Establishment of drug chests seems to be a reasonable strategy of reinforcing primary health. Much attention should be paid on training of staff, monitoring, supervision and integration of health services.

[Interest of a computerized ALS database in the diagnosis and follow-up of patients with ALS]. / Intérêts d'une base de données informatisée dans le diagnostic et le suivi de patients atteints de sclérose latérale amyotrophique.

The aim of the study is to present a computerized database of the Neurology department of Limoges University Hospital and the main results obtained from data of 340 patients suffering from amyotrophic lateral sclerosis (ALS), diagnosed between 1984 and 1997. It is a user friendly and can be accessed by all neurologists at any level of computer knowledge. This database is modular (6 modules) and flexible according to need. The software used, Access 7, is an open relation database, which allows export of data to statistical or other compatible software. One of the reasons, which led to the elaboration of this database was to develop a means of collecting data in an analyzable manner for therapeutic trials. During these trials, a great number of data can be collected during each clinic visit for the evaluation of the degree of impairment, disability, and handicap. We present part of the data from the patients followed, some of whom were treated with riluzole, the current reference molecule for ALS.

Rapidly progressive neurological deterioration in a child with Alpers syndrome exhibiting a previously unremarkable brain MRI.

Alpers syndrome is a fatal disorder due to mutations in the POLG gene encoding the catalytic subunit of mitochondrial DNA polymerase gamma (Pol gamma) involved in mitochondrial DNA (mtDNA) replication. We describe a case of Alpers syndrome due to POLG mutations, with rapidly progressive course, a fatal outcome, and an essentially normal brain MRI in the early oligo-symptomatic phase. Our observation suggests that Alpers syndrome should be considered even in patients with an initially unremarkable brain MRI. The patient was found to harbor the p.Q497H, p.W748S and p.E1143G mutations in cis on one allele, and a fourth mutation, the p.G848S on the other allele. Although the individual mutations detected in the presented case have been previously reported, the specific genotype formed by the particular combination of these is novel.

Recent invasion of the mountain birch Betula pubescens ssp. tortuosa above the treeline due to climate change: genetic and ecological study in northern Sweden.

Mountain birch, Betula pubescens ssp. tortuosa, forms the treeline in northern Sweden. A recent shift in the range of the species associated with an elevation of the treeline is commonly attributed to climate warming. Using microsatellite markers, we explored the genetic structure of populations along an altitudinal gradient close to the treeline. Low genetic differentiation was found between populations, whereas high genetic diversity was maintained within populations. High level of gene flow compensated for possible losses of genetic diversity at higher elevations and dissipated the founding effect of newly established populations above the treeline. Spatial autocorrelation analysis showed low spatial genetic structure within populations because of extensive gene flow. At the treeline, significant genetic structure within the juvenile age class at small distances did not persist in the adult age class, indicating recent expansion of young recruits due to the warming of the climate. Finally, seedling performance above the treeline was positively correlated with parameters related to temperature. These data confirm the high migration potential of the species in response to fluctuating environmental conditions and indicate that it is now invading higher altitudes due to the recent warming of the climate.

The role of platelet-activating factor in human fetal lung maturation.

The presence of the potent bioactive glycerophospholipid 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor) in a lamellar body-enriched fraction of amniotic fluid from women in labor has prompted the present investigation to examine the fetal lung as the possible tissue source of this platelet-activating factor. The metabolism of platelet-activating factor was assessed in an organ culture system in which human fetal lung tissue (12 to 16 weeks) was incubated for 6 to 7 days. During this period, the type II pneumonocytes differentiate and surfactant glycerophospholipid biosynthesis is greatly enhanced. The initial specific activity of the platelet-activating factor biosynthetic enzyme lyso-platelet-activating factor:acetyl-coenzyme A acetyltransferase is two to three times greater in microsomes prepared from fetal lung than in those from the fetal liver or kidney. The specific activity of acetyltransferase in lung tissue increased twofold after 6 days in organ culture. A similar increase in acetyltransferase activity was found in the lamellar body-enriched (18,000 X g) subcellular fraction of fetal lung. The activity of the major platelet-activating factor-inactivating enzyme platelet-activating factor acetylhydrolase did not change significantly in the lung explants during the incubation period. Associated with the enhanced platelet-activating factor biosynthetic activity in the fetal lung was an increase in the platelet-activating factor concentration, from 17 to 37 fmol/mg of protein between days 0 and 6 of culture. Corresponding increases of 3.3- and 3.8-fold in the concentrations of the platelet-activating factor lipid precursors lyso-platelet-activating factor and the 2-acyl congener were found after 6 days in culture. A reciprocal relationship was found between platelet-activating factor and glycogen content as the lung tissue matured in vitro; specifically, as the platelet-activating factor level increased, glycogen decreased from 340 to 77 micrograms/mg of protein. We suggest that platelet-activating factor may mediate the onset of glycogenolysis in fetal lung tissue similar to that in the isolated, perfused rat liver (Shukla SD, Buxton DB, Olson MS, Hanahan DJ. Acetylglyceryl ether phosphorylcholine. A potent activator of hepatic phosphoinositide metabolism and glycogenolysis. J Biol Chem 1983; 258:10212-4). The increased rate of glycogen degradation may serve as the carbon and energy source for the increased synthesis of glycerophospholipids required for surfactant production.(ABSTRACT TRUNCATED AT 400 WORDS)