Unusual manifestation of Erdheim-Chester disease

<p>Abstract</p> <p>Background</p> <p>Erdheim-Chester disease (ECD) is a rare multisystem non-Langerhans cell histiocytosis that is characterized histologically by xanthogranulomatous infiltrates and radiologically by symmetrical sclerosis of long bones. The xanthomatous process is characterized by prominent foamy histiocytes staining positive for CD68, occasionally for PS100 and negative for S100 and CD1a. Gastroenterological involvement is exceedingly rare.</p> <p>Case Presentation</p> <p>This case report describes the case of a 69-year-old man who presented otherwise well to the gastroenterology department with unspecific abdominal symptoms, nausea, vomiting and weight loss. ECD involving the gastrointestinal tract was confirmed clinically, radiologically and histologically.</p> <p>Conclusion</p> <p>Gastroenterological manifestation of ECD is rare but should be considered in the differential diagnosis in patients presenting with evidence of multi-organ disease and typical radiological features of Erdheim-Chester disease elsewhere.</p

Long noncoding RNAs are rarely translated in two human cell lines

Data from the Encyclopedia of DNA Elements (ENCODE) project show over 9640 human genome loci classified as long noncoding RNAs (lncRNAs), yet only ∼100 have been deeply characterized to determine their role in the cell. To measure the protein-coding output from these RNAs, we jointly analyzed two recent data sets produced in the ENCODE project: tandem mass spectrometry (MS/MS) data mapping expressed peptides to their encoding genomic loci, and RNA-seq data generated by ENCODE in long polyA+ and polyA− fractions in the cell lines K562 and GM12878. We used the machine-learning algorithm RuleFit3 to regress the peptide data against RNA expression data. The most important covariate for predicting translation was, surprisingly, the Cytosol polyA− fraction in both cell lines. LncRNAs are ∼13-fold less likely to produce detectable peptides than similar mRNAs, indicating that ∼92% of GENCODE v7 lncRNAs are not translated in these two ENCODE cell lines. Intersecting 9640 lncRNA loci with 79,333 peptides yielded 85 unique peptides matching 69 lncRNAs. Most cases were due to a coding transcript misannotated as lncRNA. Two exceptions were an unprocessed pseudogene and a bona fide lncRNA gene, both with open reading frames (ORFs) compromised by upstream stop codons. All potentially translatable lncRNA ORFs had only a single peptide match, indicating low protein abundance and/or false-positive peptide matches. We conclude that with very few exceptions, ribosomes are able to distinguish coding from noncoding transcripts and, hence, that ectopic translation and cryptic mRNAs are rare in the human lncRNAome

Efficacy of ovulation synchronization with timed artificial insemination in treatment of follicular cysts in dairy cows

The efficacy of five ovulation-synchronization protocols with FTAI in treatment of cows diagnosed with follicular cysts was investigated in a nonrandomized study in a single herd. Cows identified with follicular structures >25 mm on two subsequent ultrasonographic (USG) examinations 7–10 days apart (n = 552) were assigned to one of the five treatment regimens on the day of the second USG examination. Treatment regimens were Ovsynch (GnRH-7d-PGF2α-56h-GnRH-16h-FTAI), New-CIDR (as Ovsynch with a new CIDR insert being fitted between days 0 and 7), Reused-CIDR (as New-CIDR but the CIDR insert was previously used for 7 days in another cow), G-New CIDR (Pre-GnRH on day 0 with the New-CIDR regimen being initiated 7 days later), and RG-Ovsynch (Pre-GnRH on day 0 and then every 7 days until detection of a luteal structure upon USG examination; at that point the Ovsynch was initiated). A subset of cows was subjected to ovarian USG examination at the time of PGF2α administration, at insemination, and 8–10 days post-insemination. Progesterone-releasing ability of new and reused CIDR inserts were evaluated in cows diagnosed with severe ovarian inactivity (n = 16). The data were analyzed using logistic regression with pregnancy per AI on days 30 (P/Al 30) and 70 (P/AI 70) post-insemination were included as outcome measures. Compared with Ovsynch, RG-Ovsynch improved the P/AI 30 (OR = 2.6, P = 0.03) and the P/AI 70 (OR = 2.5, P = 0.05). New-CIDR and G-New CIDR were associated with non-significant increase in P/AI 30 (OR = 2.1, P = 0.09 and OR = 2.3, P = 0.07, respectively) and P/AI 70 (OR = 2.01, P = 0.09 and OR = 2.2, P = 0.09, respectively). Reused-CIDR was not associated with improvement in P/AI (P = 0.93 and 0.79 for P/AI 30 and P/AI 70, respectively). RG-Ovsynch had a longer diagnosis-to-FTAI interval (median 24, IQR 17,31). The dominant ovarian structures and the presence of a cyst or a luteal structure at PGF2α administration or at insemination were not associated with P/AI. The new and re-used CIDR inserts produced comparable concentrations of serum progesterone 3 h, 3 days and 7 days post CIDR insertion. In conclusion, the RG-Ovsynch improved the P/AI whereas the New-CIDR and the G-New CIDR regimens tended to increase the P/AI compared with Ovsynch. Marginal differences in P/AI between RG-Ovsynch, New-CIDR, and G-New-CIDR together with prolonged diagnosis-to-FTAI in RG-Ovsynch should be considered if to evaluate the economic value of these regimens

Image1_Ancestry dependent balancing selection of placental dysferlin at high-altitude.JPEG

Introduction: The placenta mediates fetal growth by regulating gas and nutrient exchange between the mother and the fetus. The cell type in the placenta where this nutrient exchange occurs is called the syncytiotrophoblast, which is the barrier between the fetal and maternal blood. Residence at high-altitude is strongly associated with reduced 3rd trimester fetal growth and increased rates of complications such as preeclampsia. We asked whether altitude and/or ancestry-related placental gene expression contributes to differential fetal growth under high-altitude conditions, as native populations have greater fetal growth than migrants to high-altitude.Methods: We have previously shown that methylation differences largely accounted for altitude-associated differences in placental gene expression that favor improved fetal growth among high-altitude natives. We tested for differences in DNA methylation between Andean and European placental samples from Bolivia [La Paz (∼3,600 m) and Santa Cruz, Bolivia (∼400 m)]. One group of genes showing significant altitude-related differences are those involved in cell fusion and membrane repair in the syncytiotrophoblast. Dysferlin (DYSF) shows greater expression levels in high- vs. low-altitude placentas, regardless of ancestry. DYSF has a single nucleotide variant (rs10166384;G/A) located at a methylation site that can potentially stimulate or repress DYSF expression. Following up with individual DNA genotyping in an expanded sample size, we observed three classes of DNA methylation that corresponded to individual genotypes of rs10166384 (A/A Results: We found that balancing selection (Tajima’s D = 2.37) was acting on this fragment among Andeans regardless of altitude, and in Europeans at high-altitude (Tajima’s D = 1.85).Discussion: This supports that balancing selection acting on dysferlin is capable of altering DNA methylation patterns based on environmental exposure to high-altitude hypoxia. This finding is analogous to balancing selection seen frequency-dependent selection, implying both alleles are advantageous in different ways depending on environmental circumstances. Preservation of the adenine (A) and guanine (G) alleles may therefore aid both Andeans and Europeans in an altitude dependent fashion.</p

Table1_Ancestry dependent balancing selection of placental dysferlin at high-altitude.DOCX

Introduction: The placenta mediates fetal growth by regulating gas and nutrient exchange between the mother and the fetus. The cell type in the placenta where this nutrient exchange occurs is called the syncytiotrophoblast, which is the barrier between the fetal and maternal blood. Residence at high-altitude is strongly associated with reduced 3rd trimester fetal growth and increased rates of complications such as preeclampsia. We asked whether altitude and/or ancestry-related placental gene expression contributes to differential fetal growth under high-altitude conditions, as native populations have greater fetal growth than migrants to high-altitude.Methods: We have previously shown that methylation differences largely accounted for altitude-associated differences in placental gene expression that favor improved fetal growth among high-altitude natives. We tested for differences in DNA methylation between Andean and European placental samples from Bolivia [La Paz (∼3,600 m) and Santa Cruz, Bolivia (∼400 m)]. One group of genes showing significant altitude-related differences are those involved in cell fusion and membrane repair in the syncytiotrophoblast. Dysferlin (DYSF) shows greater expression levels in high- vs. low-altitude placentas, regardless of ancestry. DYSF has a single nucleotide variant (rs10166384;G/A) located at a methylation site that can potentially stimulate or repress DYSF expression. Following up with individual DNA genotyping in an expanded sample size, we observed three classes of DNA methylation that corresponded to individual genotypes of rs10166384 (A/A Results: We found that balancing selection (Tajima’s D = 2.37) was acting on this fragment among Andeans regardless of altitude, and in Europeans at high-altitude (Tajima’s D = 1.85).Discussion: This supports that balancing selection acting on dysferlin is capable of altering DNA methylation patterns based on environmental exposure to high-altitude hypoxia. This finding is analogous to balancing selection seen frequency-dependent selection, implying both alleles are advantageous in different ways depending on environmental circumstances. Preservation of the adenine (A) and guanine (G) alleles may therefore aid both Andeans and Europeans in an altitude dependent fashion.</p