Fungal Planet description sheets: 868-950.

Novel species of fungi described in this study include those from various countries as follows: Australia, Chaetomella pseudocircinoseta and Coniella pseudodiospyri on Eucalyptus microcorys leaves, Cladophialophora eucalypti, Teratosphaeria dunnii and Vermiculariopsiella dunnii on Eucalyptus dunnii leaves, Cylindrium grande and Hypsotheca eucalyptorum on Eucalyptus grandis leaves, Elsinoe salignae on Eucalyptus saligna leaves, Marasmius lebeliae on litter of regenerating subtropical rainforest, Phialoseptomonium eucalypti (incl. Phialoseptomonium gen. nov.) on Eucalyptus grandis × camaldulensis leaves, Phlogicylindrium pawpawense on Eucalyptus tereticornis leaves, Phyllosticta longicauda as an endophyte from healthy Eustrephus latifolius leaves, Pseudosydowia eucalyptorum on Eucalyptus sp. leaves, Saitozyma wallum on Banksia aemula leaves, Teratosphaeria henryi on Corymbia henryi leaves. Brazil, Aspergillus bezerrae, Backusella azygospora, Mariannaea terricola and Talaromyces pernambucoensis from soil, Calonectria matogrossensis on Eucalyptus urophylla leaves, Calvatia brasiliensis on soil, Carcinomyces nordestinensis on Bromelia antiacantha leaves, Dendryphiella stromaticola on small branches of an unidentified plant, Nigrospora brasiliensis on Nopalea cochenillifera leaves, Penicillium alagoense as a leaf endophyte on a Miconia sp., Podosordaria nigrobrunnea on dung, Spegazzinia bromeliacearum as a leaf endophyte on Tilandsia catimbauensis, Xylobolus brasiliensis on decaying wood. Bulgaria, Kazachstania molopis from the gut of the beetle Molops piceus. Croatia, Mollisia endocrystallina from a fallen decorticated Picea abies tree trunk. Ecuador, Hygrocybe rodomaculata on soil. Hungary, Alfoldia vorosii (incl. Alfoldia gen. nov.) from Juniperus communis roots, Kiskunsagia ubrizsyi (incl. Kiskunsagia gen. nov.) from Fumana procumbens roots. India, Aureobasidium tremulum as laboratory contaminant, Leucosporidium himalayensis and Naganishia indica from windblown dust on glaciers. Italy, Neodevriesia cycadicola on Cycas sp. leaves, Pseudocercospora pseudomyrticola on Myrtus communis leaves, Ramularia pistaciae on Pistacia lentiscus leaves, Neognomoniopsis quercina (incl. Neognomoniopsis gen. nov.) on Quercus ilex leaves. Japan, Diaporthe fructicola on Passiflora edulis × P. edulis f. flavicarpa fruit, Entoloma nipponicum on leaf litter in a mixed Cryptomeria japonica and Acer spp. forest. Macedonia, Astraeus macedonicus on soil. Malaysia, Fusicladium eucalyptigenum on Eucalyptus sp. twigs, Neoacrodontiella eucalypti (incl. Neoacrodontiella gen. nov.) on Eucalyptus urophylla leaves. Mozambique, Meliola gorongosensis on dead Philenoptera violacea leaflets. Nepal, Coniochaeta dendrobiicola from Dendriobium lognicornu roots. New Zealand, Neodevriesia sexualis and Thozetella neonivea on Archontophoenix cunninghamiana leaves. Norway, Calophoma sandfjordenica from a piece of board on a rocky shoreline, Clavaria parvispora on soil, Didymella finnmarkica from a piece of Pinus sylvestris driftwood. Poland, Sugiyamaella trypani from soil. Portugal, Colletotrichum feijoicola from Acca sellowiana. Russia, Crepidotus tobolensis on Populus tremula debris, Entoloma ekaterinae, Entoloma erhardii and Suillus gastroflavus on soil, Nakazawaea ambrosiae from the galleries of Ips typographus under the bark of Picea abies. Slovenia, Pluteus ludwigii on twigs of broadleaved trees. South Africa, Anungitiomyces stellenboschiensis (incl. Anungitiomyces gen. nov.) and Niesslia stellenboschiana on Eucalyptus sp. leaves, Beltraniella pseudoportoricensis on Podocarpus falcatus leaf litter, Corynespora encephalarti on Encephalartos sp. leaves, Cytospora pavettae on Pavetta revoluta leaves, Helminthosporium erythrinicola on Erythrina humeana leaves, Helminthosporium syzygii on a Syzygium sp. bark canker, Libertasomyces aloeticus on Aloe sp. leaves, Penicillium lunae from Musa sp. fruit, Phyllosticta lauridiae on Lauridia tetragona leaves, Pseudotruncatella bolusanthi (incl. Pseudotruncatellaceae fam. nov.) and Dactylella bolusanthi on Bolusanthus speciosus leaves. Spain, Apenidiella foetida on submerged plant debris, Inocybe grammatoides on Quercus ilex subsp. ilex forest humus, Ossicaulis salomii on soil, Phialemonium guarroi from soil. Thailand, Pantospora chromolaenae on Chromolaena odorata leaves. Ukraine, Cadophora helianthi from Helianthus annuus stems. USA, Boletus pseudopinophilus on soil under slash pine, Botryotrichum foricae, Penicillium americanum and Penicillium minnesotense from air. Vietnam, Lycoperdon vietnamense on soil. Morphological and culture characteristics are supported by DNA barcodes.

Morpho-histology of head kidney of female catfish Heteropneustes fossilis: seasonal variations in melano-macrophage centers, melanin contents and effects of lipopolysaccharide and dexamethasone on melanins.

In the catfish Heteropneustes fossilis, the anterior kidney is a hemopoietic tissue which surrounds the adrenal homologues, interrenal (IR) and chromaffin tissues corresponding to the adrenal cortical and adrenal medulla of higher mammals. The IR tissue is arranged in cell cords around the posterior cardinal vein (PCV) and its tributaries and secretes corticosteroids. The chromaffin tissue is scattered singly or in nests of one or more cells around the epithelial lining of the PCV or blood capillaries within the IR tissue. They are ferric ferricyanide-positive. Leukemia-inhibitory factor (LIF)-like reactivity was noticed in the lining of the epithelium of the IR cell cords and around the wall of the PCV and blood capillaries. No staining was observed in the hemopoietic cells. IL-1ß- and TNF-α-like immunoreactivity was seen in certain cells in the hemopoietic tissue but not in the IR region. Macrophages were identified with mammalian macrophage-specific MAC387 antibodies and are present in the hemopoietic mass but not in the IR tissue. Pigments accumulate in the hemopoietic mass as melano-macrophage centers (MMCs) and are PAS-, Schmorl's- and Perls'-positive. The pigments contain melanin (black), hemosiderin (blue) and lipofuscin/ceroid (oxidized lipid, yellowish tan), as evident from the Perls' reaction. The MMCs were TUNEL-positive as evident from FITC fluorescence, indicating their apoptotic nature. The MMCs showed significant seasonal variation with their density increasing to the peak in the postspawning phase. Melanins were characterized spectrophotometrically for the first time in fish anterior kidney. The predominant form is pheomelanin (PM), followed by eumelanin (EM) and alkali-soluble melanin (ASM). Melanins showed significant seasonal variations with the level low in the resting phase and increasing to the peak in the postspawning phase. Under in vitro conditions, lipopolysaccharide (10 µg/mL) treatment increased significantly the levels of PM and EM levels both at 16 and at 32 h and the ASM level at 32 h. On the other hand, the synthetic glucocorticoid dexamethasone (100 nM) decreased significantly the levels of EM, PM and ASM time-dependently. The results indicate that the anterior kidney is an important site of immune-endocrine interaction.

Zygomycosis caused by Rhizopus microsporus and Rhizopus oryzae in Madhya Pradesh (M.P.) Central India: a report of two cases.

Zygomycosis encompasses infections due to two distinct orders of fungi, Mucorales and Entomophthorales. With rare exception, Entomophthorales are restricted to tropical areas. By contrast, mucorales are ubiquitous opportunistic fungi, which play a crucial part in the natural decay process. In human pathology, they may be opportunistic agents and be responsible for rare infection called (Mucormycosis) zygomycosis. We report two cases of zygomycosis from Madhya Pradesh, Central India, one caused by Rhizopus oryzae in a diabetic patient and another caused by Rhizopus microsporus in an apparently healthy patient. The cases were diagnosed by direct microscopy, histopathological examination and culture. Both the patients were successfully treated with liposomal amphotericin B. Rhizopus microsporus is, for the first time reported from Madhya Pradesh, India, causing rhino-maxillary orbital zygomycosis.

Comparison of bacterial diversity in proglacial soil from Kafni Glacier, Himalayan Mountain ranges, India, with the bacterial diversity of other glaciers in the world.

Two 16S rRNA gene clone libraries (KF and KS) were constructed using two soil samples (K7s and K8s) collected near Kafni Glacier, Himalayas. The two libraries yielded a total of 648 clones. Phyla Actinobacteria, Bacteroidetes, Chloroflexi Firmicutes, Proteobacteria, Spirochaetae, Tenericutes and Verrucomicrobia were common to the two libraries. Phyla Acidobacteria, Chlamydiae and Nitrospirae were present only in KF library, whereas Lentisphaerae and TM7 were detected only in KS. In the two libraries, clones belonging to phyla Bacteroidetes and Proteobacteria were the most predominant. Principal component analysis (PCA) revealed that KF and KS were different and arsenic content influenced the differences in the percentage of OTUs. PCA indicated that high water content in the K8s sample results in high total bacterial count. PCA also indicated that bacterial diversity of KF and KS was similar to soils from the Pindari Glacier, Himalayas; Samoylov Island, Siberia; Schrimacher Oasis, Antarctica and Siberian tundra. The eleven bacterial strains isolated from the above two soil samples were phylogenetically related to six different genera. All the isolates were psychro-, halo- and alkalitolerant. Amylase, lipase and urease activities were detected in the majority of the strains. Long chain, saturated, unsaturated and branched fatty acids were predominant in the psychrotolerant bacteria.

A prospective cohort study on predictors of mortality of delirium in an emergency observational unit.

BACKGROUND: Delirium is often an underdiagnosed and underestimated neuropsychiatric syndrome, especially in low- and middle-income countries. AIM: To document the prevalence and clinical profile of delirium and to detect the baseline parameters associated with in-hospital mortality. DESIGN: A prospective cohort study conducted between January 2016 to December 2016 at an adult medical emergency observational unit of an academic hospital in north India. METHODS: Confusion Assessment Method for the intensive care unit was used for screening and diagnosis of delirium. Subtypes of delirium and severity were defined with the Richmond agitation-sedation scale and Delirium Rating Scale-Revised-98 (DRS-R-98). RESULTS: Out of 939 screened patients, 312 (33.2%) had delirium, including 73.7% unrecognized cases. The mean age was 49.1 ± 17.3 years (range 17-90), and only 33.3% of the patients were above 60 years. The prevalence of hypoactive, mixed and hyperactive delirium was 39.1, 33.7 and 27.2%, respectively. Usual predisposing factors were alcohol use disorder (57.4%) and hypertension (51.0%), and infections remain the most common precipitating factors (42.0%). In total, 96.1% of patients received midazolam before delirium onset, and physical restraints were used in 73.4%. Mortality was higher in delirium (19.9% vs. 6.4%). The independent predictors of death in delirium were low diastolic blood pressure (P-value = 0.000), Glasgow coma scale score <15 (P = 0.026), high Acute Physiology and Chronic Health Evaluation II score (P = 0.007), high DRS-R-98 severity score (P = 0.000) and hyperactive delirium (P = 0.024). CONCLUSION: Rapid screening with Confusion Assessment Method for the intensive care unit detected a high prevalence of delirium (even in young patients), and it associated with high mortality.

Copy number variation showers in schizophrenia: an emerging hypothesis.

Genetic discoveries on Schizophrenia remain challenging. Traditional approaches have provided clues, but no genes. Novel theories that must account for extensive heterogeneity, including high discordance of monozygotic (MZD) twins, are needed. To this end, the extensive repeats of the human genome may provide the predisposition for DNA replication errors operational at every cell cycle during meiosis and mitosis. These errors will shower the genome with replication errors including copy number variations. Depending on the timing and the genes involved, this will contribute to the mutational load and disease. The evidence for such a mechanism in schizophrenia is emerging.

Studies on Syntaxin 12 and alcohol preference involving C57BL/6J and DBA/2J strains of mice.

C57BL/6J and DBA/2J inbred mouse strains have been extensively studied for the genetic dissection of alcohol-related phenotypes. We have previously found Syntaxin 12 to be associated with alcohol preference in C57BL/6J and DBA/2J due to its strain-specific and ethanol responsive expression in the male brain. In the current study, we combined genetic and expression analyses to assess the segregation of Syntaxin 12 c.*1370G>A polymorphism with its strain-specific expression and alcohol preference in an F (2) population (N = 427) derived from C57BL/6J and DBA/2J strains. Syntaxin 12 c.*1370G>A polymorphism was found to segregate with alcohol preference in the B6D2F2 population and a correlation was identified between Syntaxin 12 expression and alcohol preference in the selected B6D2F2 males (r = -0.473, r (2) = 0.22). We followed up our analysis in the BXD RI lines using resources from WebQTL and the Mouse Phenome Database. Our study detected significant associations of Syntaxin 12 molecular variants with its level of expression and alcohol preference in B6D2F2 males. Overall, our findings support a role for Syntaxin 12 as a potential contributor to alcohol preference in mice.

Bacterial diversity and bioprospecting for cold-active lipases, amylases and proteases, from culturable bacteria of kongsfjorden and Ny-alesund, Svalbard, Arctic.

Culturable bacterial diversity of seven marine sediment samples of Kongsfjorden and a sediment and a soil sample from Ny-Alesund, Svalbard, Arctic was studied. The bacterial abundance in the marine sediments of Kongsfjorden varied marginally (0.5 x 10(3)-1.3 x 10(4) cfu/g sediment) and the bacterial number in the two samples collected from the shore of Ny-Alesund also was very similar (0.6 x 10(4) and 3.4 x 10(4), respectively). From the nine samples a total of 103 bacterial isolates were obtained and these isolates could be grouped in to 47 phylotypes based on the 16S rRNA gene sequence belonging to 4 phyla namely Actinobacteria, Bacilli, Bacteroidetes and Proteobacteria. Representatives of the 47 phylotypes varied in their growth temperature range (4-37 degrees C), in their tolerance to NaCl (0.3-2 M NaCl) and growth pH range (2-11). Representatives of 26 phylotypes exhibited amylase and lipase activity either at 5 or 20 degrees C or at both the temperatures. A few of the representatives exhibited amylase and/or lipase activity only at 5 degrees C. None of the phylotypes exhibited protease activity. Most of the phylotypes (38) were pigmented. Fatty acid profile studies indicated that short chain fatty acids, unsaturated fatty acids, branched fatty acids, the cyclic and the cis fatty acids are predominant in the psychrophilic bacteria.

Proteomic identification of C/EBP-DBD multiprotein complex: JNK1 activates stem cell regulator C/EBPalpha by inhibiting its ubiquitination.

Functional inactivation of transcription factors in hematopoietic stem cell development is involved in the pathogenesis of acute myeloid leukemia (AML). Stem cell regulator C/enhancer binding protein (EBP)alpha is among such transcription factors known to be inactive in AML. This is either due to mutations or inhibition by protein-protein interactions. Here, we applied a mass spectrometry-based proteomic approach to systematically identify putative co-activator proteins interacting with the DNA-binding domain (DBD) of C/EBP transcription factors. In our proteomic screen, we identified c-Jun N-terminal kinase (JNK) 1 among others such as PAK6, MADP-1, calmodulin-like skin proteins and ZNF45 as proteins interacting with DBD of C/EBPs from nuclear extract of myelomonocytic U937 cells. We show that kinase JNK1 physically interacts with DBD of C/EBPalpha in vitro and in vivo. Furthermore, we show that active JNK1 inhibits ubiquitination of C/EBPalpha possibly by phosphorylating in its DBD. Consequently, JNK1 prolongs C/EBPalpha protein half-life leading to its enhanced transactivation and DNA-binding capacity. In certain AML patients, however, the JNK1 mRNA expression and its kinase activity is decreased which suggests a possible reason for C/EBPalpha inactivation in AML. Thus, we report the first proteomic screen of C/EBP-interacting proteins, which identifies JNK1 as positive regulator of C/EBPalpha.

Multiple ways of C/EBPalpha inhibition in myeloid leukaemia.

Transcription factors play a crucial role in myeloid differentiation and lineage determination. Tumour suppressor protein C/EBPalpha is a key regulator of granulocytic differentiation whose functional inactivation has become a pathophysiological signature of myeloid leukaemia. In this review we describe various mechanisms such as antagonistic protein-protein interaction, mutation and posttranslational modifications of C/EBPalpha which lead to its transcriptional inhibition and render C/EBPalpha inactive in its functions.

Metabolic syndrome & psychiatric disorders.

The metabolic syndrome, a constellation of symptoms associated with obesity, dyslipidaemia, insulin insensitivity, deranged glucose metabolism and hypertension has been gaining widespread interest due to its immense clinical relevance. We review the metabolic syndrome in terms of its diagnostic criteria and its relationship with severe mental illnesses and psychotropic medications, and the guidelines to manage it.

Post-zygotic genomic changes in glutamate and dopamine pathway genes may explain discordance of monozygotic twins for schizophrenia.

BACKGROUND: Monozygotic twins are valuable in assessing the genetic vs environmental contribution to diseases. In the era of complete genome sequences, they allow identification of mutational mechanisms and specific genes and pathways that offer predisposition to the development of complex diseases including schizophrenia. METHODS: We sequenced the complete genomes of two pairs of monozygotic twins discordant for schizophrenia (MZD), including one representing a family tetrad. The family specific complete sequences have allowed identification of post zygotic mutations between MZD genomes. It allows identification of affected genes including relevant network and pathways that may account for the diseased state in pair specific patient. RESULTS: We found multiple twin specific sequence differences between co-twins that included small nucleotides [single nucleotide variants (SNV), small indels and block substitutions], copy number variations (CNVs) and structural variations. The genes affected by these changes belonged to a number of canonical pathways, the most prominent ones are implicated in schizophrenia and related disorders. Although these changes were found in both twins, they were more frequent in the affected twin in both pairs. Two specific pathway defects, glutamate receptor signaling and dopamine feedback in cAMP signaling pathways, were uniquely affected in the two patients representing two unrelated families. CONCLUSIONS: We have identified genome-wide post zygotic mutations in two MZD pairs affected with schizophrenia. It has allowed us to use the threshold model and propose the most likely cause of this disease in the two patients studied. The results support the proposition that each schizophrenia patient may be unique and heterogeneous somatic de novo events may contribute to schizophrenia threshold and discordance of the disease in monozygotic twins.

CpG methylation accounts for a recurrent mutation (c.1222C>T) in the human PAH gene.

The human PAH gene (GenBank: U49897.1 (cDNA), AF404777 (gDNA)) harbors alleles that either cause or are associated with hyperphenylalaninemia and phenylketonuria (http://www.pahdb.mcgill.ca). Mutation analysis has identified approximately 500 alleles of which approximately 30 produce polymorphic core haplotypes. The c.1222C>T allele (p.R408W) is the most prevalent and widely encountered PKU-causing allele. Because it occurs on multiple locus-specific polymorphic haplotypes, it is probably not identical by descent in different populations. This mutation involves a CpG dinucleotide in a so-called "hypermutable" codon suggesting that c.1222C>T could be a recurrent allele following spontaneous methylation-mediated deamination of 5 mC. This concept is widely assumed and accepted but the 5mC status of hypermutable codons has seldom been confirmed. We show that the PAH c.1222C nucleotide is indeed methylated (c.1222 mC) in somatic genomes (leukocyte and brain) of H. sapiens. Examination of a representative region in exon 12 (and also in exon 7) in the PAH gene shows that 5 mC is restricted to cytosines in CpG dinucleotides in the hypermutable codons. The methylation pattern seen in human PAH exon 12 was also observed in the corresponding codon in three nonhuman primates. The finding offers at least one explanation for the high relative frequency of the c.1222C>T (p.R408W) allele in the human population.

Blockade of the stimulatory effect of estrogens, OH-tamoxifen, OH-toremifene, droloxifene, and raloxifene on alkaline phosphatase activity by the antiestrogen EM-800 in human endometrial adenocarcinoma Ishikawa cells.

Although temporary benefits of tamoxifen therapy are observed in up to 40% of women with breast cancer, this compound, which is known to possess mixed estrogenic and antiestrogenic activities, has been associated with increased risk of endometrial carcinoma. This study compares the effects of the novel nonsteroidal pure antiestrogen EM-800 and related compounds with those of a series of antiestrogens on the estrogen-sensitive alkaline phosphatase (AP) activity in human endometrial adenocarcinoma Ishikawa cells. Exposure to increasing concentrations of up to 1000 nM EM-800 or its active metabolite EM-652 alone failed to affect basal AP activity. In contrast, incubation with 10 nM (Z)-4-OH-tamoxifen, (Z)-4-OH-toremifene, droloxifene, or raloxifene increased the value of this estrogen-sensitive parameter by 3.3-, 3.5-, 2.2-, and 1.6-fold, respectively, a stimulatory effect that was completely reversed by simultaneous exposure to 30 nM EM-800. Moreover, the stimulation of AP activity induced by 1 nM 17beta-estradiol was completely reversed by EM-800, EM-652, or ICI-182780, at the IC50 value of 1.98 +/- 0.23, 1.01 +/- 0.16, and 5.64 +/- 0.59 nM, respectively, whereas the partial blockade exerted by (Z)-4-OH-tamoxifen, (Z)-4-OH-toremifene, or raloxifene was observed at IC50 values of 13.5 +/- 3.80, 41.0 +/- 7.2, and 3.74 +/- 0.43 nM, respectively. Thus, as assessed by their activity in the human Ishikawa endometrial carcinoma cells, EM-800 and EM-652 are the most potent known antiestrogens in Ishikawa cells, and, most importantly, they are devoid of the estrogenic activity observed in these human endometrial cancer cells with (Z)-4-OH-tamoxifen, (Z)-4-OH-toremifene, droloxifene, and raloxifene.

Site-specific DNA methylation in the neurofibromatosis (NF1) promoter interferes with binding of CREB and SP1 transcription factors.

Tumour suppressor genes and growth regulatory genes are frequent targets for methylation defects that can result in aberrant expression and mutagenesis. We have established a methylation map of the promoter region of the neurofibromatosis (NF1) gene and demonstrated functional sensitivity for methylation at specific sites for the SP1 and CRE binding (CREB) proteins in the NF1 regulatory region. We evaluated the methylation status of CpG dinucleotides within five promoter subregions in the human and mouse homologues of the neurofibromatosis (NF1) genes. Three 5' subregions were found to be consistently methylated in all the tissues analysed. In contrast, DNA methylation was absent in the vicinity of the transcription start site bounded by SP1 recognition sequences. Gelshift assays showed that methylation specifically inhibits the CREB transcription factor from binding to its recognition site at the NF1 transcription start site. Furthermore, SP1 elements within the NF1 promoter are methylation sensitive, particularly when methylation is present on the antisense strand. We propose that for NF1 as with several other tumour suppressor genes, CpG methylation occurs in a complex, site-specific manner with the maintenance of a methylation-free promoter region bounded by SP1 binding sites that allow an accessible promoter to be retained. When these SP1 boundaries are breached, methylation can sweep in, rendering the promoter inaccessible for specific methylation-sensitive transcription factors and leading to a loss of functional integrity of the methylation-free CpG island.

CpG methylation within the 5' regulatory region of the BRCA1 gene is tumor specific and includes a putative CREB binding site.

Breast cancer is a genetic disease arising from a series of germ-line and/or somatic DNA changes in a variety of genes, including BRCA1 and BRCA2. DNA modifications have been shown to occur by a number of mechanisms that include DNA methylation. In some cases, the aberrant methylation of CpGs within 5' regulatory regions has led to suppression of gene activity. In this report we describe a variation in the pattern of DNA methylation within the regulatory region of the BRCA1 gene. We found no evidence of methylation at CpGs within the BRCA1 promoter in a variety of normal human tissues. However, screening of a series of randomly sampled breast carcinomas revealed the presence of CpG methylation adjacent to the BRCA1 transcription start site. One such methylated CpG occurs at a putative CREB (cAMP-responsive element binding) transcription factor binding site in the BRCA1 promoter. Gelshift assays with methylated and unmethylated BRCA1/CREB binding site oligonucleotides demonstrate that this site is sensitive to site-specific CpG methylation. These data suggest that aberrant DNA methylation at regulatory sequences in the BRCA1 locus may play a role in the transcriptional inactivation of the BRCA1 gene within subclones of breast tumors. This study represents the first evidence suggesting a role for DNA methylation in the transcriptional inactivation of the BRCA1 in human breast cancer.

Search for retroviral related DNA polymorphisms using RAPD PCR in schizophrenia.

Random amplification of polymorphic DNA (RAPD) is widely used to detect polymorphisms in many organisms. Individual (or strain) specific amplified bands are generated with single or pairs of primers in PCR reactions and can serve as genetic markers. We have used this method to generate a large number of reproducible bands with single primers, random and retroviral related, on 92 human DNA samples. Theoretically, RAPD PCR presents a logical approach for assessing variability among individuals. We used ten retroviral related primers (12, 20 and 22 bp) and eight random primers (10 bp) to assess individual differences in the context of testing the retroviral hypothesis for schizophrenia. Three pairs of discordant monozygotic twins, four pairs of discordant full sibs and 53 schizophrenic individuals with 25 of their unrelated matched controls were analyzed. Ten of these primers resulted in a total of approx. 850 amplified bands (65-110 bands per primer). Almost all of these bands were identical among each individual analyzed. However, the results are inconclusive with respect to the retroviral hypothesis for schizophrenia. The general lack of RAPD polymorphism in this study may argue for mechanisms other than rearrangements such as inversions, associated with the evolution of the human genome.

Cyclophosphamide-induced in vivo sister chromatid exchanges (SCE) in Mus musculus. III. Quantitative genetic analysis.

In vivo cyclophosphamide (CP)-induced sister chromatid exchanges (SCEs) were evaluated in females from five genetic strains of mice (C57BL/6J, C3H/S, 129/ReJ, BALB/c and DBA/2) and their F1 hybrids. Baseline (noninduced) SCE values differ significantly among strains, 129/ReJ having the lowest and DBA/2 having the highest mean SCE per cell values. In general, the baseline SCE of a given F1 is within the range of its corresponding parental strains or near the lower parental value. Furthermore, there is a genotype-dependent increase in mean SCEs per cell with CP dose. Strain differences in SCE induction are noted particularly at the two higher CP doses (4.50 and 45.0 mg/kg). In general, F1 hybrids involving a strain with high induced SCEs and a strain with low induced SCEs exhibit mean SCE values that are closer to the value of the lower strain. F1s involving two strains with high SCEs or two strains with low SCEs yield SCEs not different from parental strains. The method of diallel cross analysis showed the order of dominance of these strains in SCE induction to be 129/ReJ BALB/c C3H/S DBA/2 C57BL/6J. These results support the involvement of predominantly nonadditive genetic factors as major gene(s) in SCE induction. In addition, involvement of random and independent events in SCE induction is suggested by the distribution of SCEs which follows a Poisson distribution.