scholarly journals A Developmental Bias in Reading Frame Usage by Human Fetal Thymic TCRBDJ Transcripts is not Present in Genomic TCRBDJ Rearrangements

1999 ◽  
Vol 7 (1) ◽  
pp. 9-15
Author(s):  
James F. George ◽  
Yasushi Matsuura ◽  
Jacquelyn A. Byrne ◽  
Eugene L. Liu ◽  
Denise R. Shaw ◽  
...  

We have previously reported that reading-frame usage and functional diversification is developmentally regulated, with virtually all TCRB DJ mRNA transcripts using a single reading frame at 8 weeks of gestational age, tapering to 50% by adult life. We used the polymerase chain reaction to create genomic libraries of DJ rearrangements in the TCRB locus from thymuses at 7.7, 10, and 16 weeks of gestational age, and from adult thymuses. Clones were randomly picked and sequenced to determine junctional sequences and reading-frame utilization. The resulting data address the hypothesis that cells bearing genomic joints in reading frame one are preferentially selected during fetal life. This hypothesis predicts that reading- frame bias would also be observed among genomic DJ joints. Instead, we observed random utilization of the three possible D-region reading frames among genomic D1s1 => J1s1 joints during fetal life. Similar results were obtained at 7.7 weeks of gestational age in a second thymus in which both RNA and DNA were simultaneously isolated and used to create libraries of TCRBDJ transcripts or rearrangements. We conclude that reading-frame utilization is random among genomic D1s1-JB1s1 rearrangements and that the preferential usage of a single reading frame among mRNA transcripts of TCRB DJ transcripts is the result of preferential transcription of genomic TCRB DJ joints in a single reading frame, or that TCRB DJ transcripts have a longer half-life than transcripts in reading frames two or three.

1998 ◽  
Vol 72 (3) ◽  
pp. 2150-2159 ◽  
Author(s):  
Pius Spielhofer ◽  
Thomas Bächi ◽  
Thomas Fehr ◽  
Gudrun Christiansen ◽  
Roberto Cattaneo ◽  
...  

ABSTRACT Measles virus (MV) and vesicular stomatitis virus (VSV) are both members of the Mononegavirales but are only distantly related. We generated two genetically stable chimeric viruses. In MGV, the reading frames of the MV envelope glycoproteins H and F were substituted by a single reading frame encoding the VSV G glycoprotein; MG/FV is similar but encodes a G/F hybrid in which the VSV G cytoplasmic tail was replaced by that of MV F. In contrast to MG/FV, MGV virions do not contain the MV matrix (M) protein. This demonstrates that virus assembly is possible in the absence of M; conversely, the cytoplasmic domain of F allows incorporation of M and enhances assembly. The formation of chimeric viruses was substantially delayed and the titers obtained were reduced about 50-fold in comparison to standard MV. In the novel chimeras, transcription and replication are mediated by the MV ribonucleoproteins but the envelope glycoproteins dictate the host range. Mice immunized with the chimeric viruses were protected against lethal doses of wild-type VSV. These findings suggest that it is feasible to construct MV variants bearing a variety of different envelopes for use as vaccines or for gene therapeutic purposes.


2020 ◽  
Vol 149 ◽  
pp. 105154 ◽  
Author(s):  
Elaine Luiza Santos Soares de Mendonça ◽  
Mateus de Lima Macêna ◽  
Nassib Bezerra Bueno ◽  
Alane Cabral Menezes de Oliveira ◽  
Carolina Santos Mello

1988 ◽  
Vol 8 (9) ◽  
pp. 3827-3836
Author(s):  
N P Williams ◽  
P P Mueller ◽  
A G Hinnebusch

Translational control of GCN4 expression in the yeast Saccharomyces cerevisiae is mediated by multiple AUG codons present in the leader of GCN4 mRNA, each of which initiates a short open reading frame of only two or three codons. Upstream AUG codons 3 and 4 are required to repress GCN4 expression in normal growth conditions; AUG codons 1 and 2 are needed to overcome this repression in amino acid starvation conditions. We show that the regulatory function of AUG codons 1 and 2 can be qualitatively mimicked by the AUG codons of two heterologous upstream open reading frames (URFs) containing the initiation regions of the yeast genes PGK and TRP1. These AUG codons inhibit GCN4 expression when present singly in the mRNA leader; however, they stimulate GCN4 expression in derepressing conditions when inserted upstream from AUG codons 3 and 4. This finding supports the idea that AUG codons 1 and 2 function in the control mechanism as translation initiation sites and further suggests that suppression of the inhibitory effects of AUG codons 3 and 4 is a general consequence of the translation of URF 1 and 2 sequences upstream. Several observations suggest that AUG codons 3 and 4 are efficient initiation sites; however, these sequences do not act as positive regulatory elements when placed upstream from URF 1. This result suggests that efficient translation is only one of the important properties of the 5' proximal URFs in GCN4 mRNA. We propose that a second property is the ability to permit reinitiation following termination of translation and that URF 1 is optimized for this regulatory function.


F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 155 ◽  
Author(s):  
Sandeep Chakraborty ◽  
Monica Britton ◽  
Jill Wegrzyn ◽  
Timothy Butterfield ◽  
Pedro José Martínez-García ◽  
...  

The transcriptome provides a functional footprint of the genome by enumerating the molecular components of cells and tissues. The field of transcript discovery has been revolutionized through high-throughput mRNA sequencing (RNA-seq). Here, we present a methodology that replicates and improves existing methodologies, and implements a workflow for error estimation and correction followed by genome annotation and transcript abundance estimation for RNA-seq derived transcriptome sequences (YeATS - Yet Another Tool Suite for analyzing RNA-seq derived transcriptome). A unique feature of YeATS is the upfront determination of the errors in the sequencing or transcript assembly process by analyzing open reading frames of transcripts. YeATS identifies transcripts that have not been merged, result in broken open reading frames or contain long repeats as erroneous transcripts. We present the YeATS workflow using a representative sample of the transcriptome from the tissue at the heartwood/sapwood transition zone in black walnut. A novel feature of the transcriptome that emerged from our analysis was the identification of a highly abundant transcript that had no known homologous genes (GenBank accession: KT023102). The amino acid composition of the longest open reading frame of this gene classifies this as a putative extensin. Also, we corroborated the transcriptional abundance of proline-rich proteins, dehydrins, senescence-associated proteins, and the DNAJ family of chaperone proteins. Thus, YeATS presents a workflow for analyzing RNA-seq data with several innovative features that differentiate it from existing software.


1977 ◽  
Vol 46 (5) ◽  
pp. 609-617 ◽  
Author(s):  
W. James Gardner ◽  
Herbert S. Bell ◽  
Pete N. Poolos ◽  
Donald F. Dohn ◽  
Marta Steinberg

✓ The clinical course of 12 patients who underwent terminal ventriculostomy for syringomyelia is presented. Opening the central canal at the tip of the conus medullaris is a relatively benign procedure that improves the symptoms of syringomyelia and syringobulbia. This canal normally terminates at the tip of the conus, but in each of the 12 surgical specimens it continued into the filum terminale for distances up to 8 cm. In most cases the tip of the conus was located more caudally than normal, indicating some degree of tethering in fetal life. This belief is supported by the fact that the newborn, whose conus is tethered to a lipoma at the sacral level, may develop syringomyelia in adult life.


2008 ◽  
Vol 295 (2) ◽  
pp. R543-R549 ◽  
Author(s):  
Analía Lorena Tomat ◽  
Felipe Inserra ◽  
Luciana Veiras ◽  
María Constanza Vallone ◽  
Ana María Balaszczuk ◽  
...  

Intrauterine and postnatal zinc restriction may result in an adverse environment for the development of cardiovascular and renal systems. This study evaluated the effects of moderate zinc deficiency during fetal life, lactation, and/or postweaning growth on systolic blood pressure, renal function, and morphology in adult life. Female Wistar rats received low (8 ppm) or control (30 ppm) zinc diets from the beginning of pregnancy up to weaning. After weaning, male offspring of each group of mothers were fed low or control zinc diet. Systolic blood pressure, creatinine clearance, proteinuria, renal morphology, renal apoptosis. and renal oxidative stress state were evaluated after 60 days. Zinc deficiency during pre- and postweaning growth induced an increase in systolic blood pressure and a decrease in the glomerular filtration rate associated with a reduction in the number and size of nephrons. Activation of renal apoptosis, reduction in catalase activity, glutathione peroxidase activity, and glutathione levels and increase in lipid peroxidation end products could explain these morphometric changes. Zinc deficiency through pre- and postweaning growth induced more pronounced renal alteration than postweaning zinc deficiency. These animals showed signs of renal fibrosis, proteinuria, increased renal apoptosis, and higher lipid peroxidation end products. A control diet during postweaning growth did not totally overcome renal oxidative stress damage, apoptosis, and fibrosis induced by zinc deficiency before weaning. In conclusion, zinc deficiency during a critical period of renal development and maturation could induce functional and morphological alterations that result in elevated blood pressure and renal dysfunction in adult life.


1995 ◽  
Vol 5 (3) ◽  
pp. 272-274 ◽  
Author(s):  
Gurleen Kaur Sharland ◽  
Shakeel Ahmed Qureshi

SummaryA case of a complete atrioventricular septal defect was detected in a 20-week gestation fetus, in whom the ventricular component of the defect was subsequently noted to close spontaneously with advancing gestational age. The antenatal and postnatal findings are discussed.


1993 ◽  
Vol 9 (1) ◽  
pp. 15-23 ◽  
Author(s):  
J. Fellague Ariouat ◽  
D.J.P. Barker

Recent research has shown that retarded growth during fetal life and infancy is linked to the development of cardiovascular disease (coronary heart disease and stroke) in adult life. Maternal nutrition has an important effect on early growth and the diets of young women may therefore influence cardiovascular disease in the next generation. Samples of women aged 80 years and over were interviewed in six areas of England and Wales with different cardiovascular death rates. The women, 281 in total, were asked about their diets when they were aged 10 to 15 years. Those who grew up in areas which now have low cardiovascular mortality tended to eat four meals a day rather than three, to live in households which had gardens, kept hens or livestock, and to go into domestic service, where diets were generally good. Those who grew up in areas which now have high cardiovascular mortality tended to eat less red meat, to live in houses without gardens, to enter industrial occupations and have higher fertility rates.


2010 ◽  
Vol 92 (7) ◽  
pp. e15-e18 ◽  
Author(s):  
Thomas Hanna ◽  
Jacob A Akoh

Introduction Intestinal malrotation is a rare developmental abnormality occurring as a result of incomplete rotation during fetal life. It usually presents in the first few weeks of life, but may persist unrecognised into adult life. We report two interesting cases in elderly patients both characterised by a significant diagnostic challenge due to atypical clinical and radiological signs and in one case an unusual complication following laparotomy. Case Reports The first case was a 64-year-old man initially treated for diverticulitis but at laparotomy was found to have malrotation of the midgut and a perforated left-sided appendicitis. The second case was a 76-year-old woman admitted with multiple fractures and increasing abdominal distension following a fall. Ten days after admission, she underwent right hemicolectomy to treat faecal peritonitis due to multiple caecal perforations complicating volvulus in the presence of midgut malrotation. Conclusions These cases illustrate challenges associated with managing patients with undiagnosed intestinal malrotation. Delayed diagnosis is a common feature in several case reports describing atypical presentation of appendicitis in patients with malrotation. While abdominal CT scan can remove much of the diagnostic uncertainty, the diagnosis of malrotation can be missed unless there is a high index of suspicion.


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