Unique XCI evolution in Tokudaia: initial XCI of the neo-X chromosome in Tokudaia muenninki and function loss of XIST in Tokudaia osimensis

ABSTRACT An average size chromomere of the polytene X chromosome of Drosophila melanogaster contains enough DNA in each haploid equivalent strand to code for 30 genes, each 1,000 nucleotides long. We have attempted to learn about the organization of chromosomes by asking how many functional units can be localized within a chromomere. This was done by 1) recovery of mutants representative of every cistron in the 3A2-3C2 region; 2) the characterization of the function of each mutant type and grouping by complementation tests; 3) the determination of the genetic and cytological position of each cistron by recombination and deletion mapping. The data clearly show one functional group per chromomere. It is postulated that a chromomere is one cistron within which much of the DNA is regulatory in function.

Download Full-text

Comparison between Tc-99m DMSA and Renal Ultrasonography for the Evaluation of Renal Scarring and Function Loss in Children with Spina Bifida

Istanbul Medical Journal ◽

10.5152/imj.2017.67625 ◽

2017 ◽

Vol 18 (2) ◽

pp. 76-79

Author(s):

Ebru Ozgonenel ◽

Isik Karalok ◽

Emel Ceylan Gunay ◽

Tomris Duymaz ◽

Ibrahim Alatas ◽

...

Keyword(s):

Spina Bifida ◽

Renal Scarring ◽

Renal Ultrasonography ◽

Function Loss ◽

And Function

Download Full-text

A primate-specific retroviral enhancer wires the XACT lncRNA into the core pluripotency network in human

10.1101/693416 ◽

2019 ◽

Cited By ~ 1

Author(s):

Miguel Casanova ◽

Madeleine Moscatelli ◽

Louis Édouard Chauvière ◽

Christophe Huret ◽

Julia Samson ◽

...

Keyword(s):

X Chromosome ◽

Regulatory Networks ◽

Embryonic Stem ◽

Endogenous Retroviruses ◽

Striking Difference ◽

X Chromosomes ◽

Regulatory Pathways ◽

Active Coating ◽

Species Specific ◽

And Function

AbstractTransposable elements (TEs) have been of paramount importance in shaping genomic and epigenomic landscapes of their hosts and in driving the expansion of gene regulatory networks during mammalian evolution. They are found in nearly all long non-coding RNAs (lncRNAs) and have promoted their evolution and function, often in a species- and tissue-specific manner. X-chromosome inactivation (XCI) is an essential process that relies on several TE-enriched lncRNAs. While XCI is conserved across species, one striking difference between human and mouse is the existence of XACT (X active coating transcript), a human-specific lncRNA that coats active X chromosomes in pluripotent cells and may oppose X chromosome silencing in this context. Here, we explore how different families of TEs have contributed to shaping the XACT locus and how they couple its expression to pluripotency in humans. Through a combination of sequence analysis across primates, transcriptional interference and genome editing in human embryonic stem cells (hESCs), we identify a critical enhancer for the transcriptional regulation of the XACT locus that evolved from an ancestral group (LTR48B/ERV1) of mammalian endogenous retroviruses (ERVs), prior to the emergence of XACT. Furthermore, we show that this ancient ERV was hijacked by evolutionarily younger hominoid-specific ERVs that gave rise to the promoter of XACT, thus wiring its expression to the pluripotency network. This work illustrates how retroviral-derived sequences may intervene in species-specific regulatory pathways.

Download Full-text

Angiotensin 1‐7 reduces muscle atrophy and function loss following 16 week denervation

The FASEB Journal ◽

10.1096/fasebj.2020.34.s1.03960 ◽

2020 ◽

Vol 34 (S1) ◽

pp. 1-1

Author(s):

Jean-Marc Renaud ◽

Hind Albadrani

Keyword(s):

Muscle Atrophy ◽

Function Loss ◽

And Function

Download Full-text

Oxygenation of the Intraportally Transplanted Pancreatic Islet

Journal of Diabetes Research ◽

10.1155/2016/7625947 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 18

Author(s):

Thomas M. Suszynski ◽

Efstathios S. Avgoustiniatos ◽

Klearchos K. Papas

Keyword(s):

Volume Fraction ◽

Islet Cells ◽

Thrombus Formation ◽

Reaction Model ◽

Diffusion Reaction ◽

Loss Of Function ◽

Islet Volume ◽

Function Loss ◽

Average Size ◽

And Function

Intraportal islet transplantation (IT) is not widely utilized as a treatment for type 1 diabetes. Oxygenation of the intraportally transplanted islet has not been studied extensively. We present a diffusion-reaction model that predicts the presence of ananoxiccore and a largerpartly functionalcore within intraportally transplanted islets. Four variables were studied: islet diameter, islet fractional viability, external oxygen partial pressure (P) (in surrounding portal blood), and presence or absence of a thrombus on the islet surface. Results indicate that an islet with average size and fractional viability exhibits an anoxic volume fraction (AVF) of 14% and a function loss of 72% at a low externalP. Thrombus formation increased AVF to 30% and function loss to 92%, suggesting that the effect of thrombosis may be substantial. ExternalPand islet diameter accounted for the greatest overall impact on AVF and loss of function. At our institutions, large human alloislets (>200μm diameter) account for ~20% of total islet number but ~70% of total islet volume; since most of the total transplanted islet volume is accounted for by large islets, most of the intraportal islet cells are likely to be anoxic and not fully functional.

Download Full-text

Urocortin II Treatment Reduces Skeletal Muscle Mass and Function Loss During Atrophy and Increases Nonatrophying Skeletal Muscle Mass and Function

Endocrinology ◽

10.1210/en.2003-0271 ◽

2003 ◽

Vol 144 (11) ◽

pp. 4939-4946 ◽

Cited By ~ 28

Author(s):

Richard T. Hinkle ◽

Elizabeth Donnelly ◽

David B. Cody ◽

Mary Beth Bauer ◽

Robert J. Isfort

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Function Loss ◽

And Function

Download Full-text

Circular RNA CREBBP Suppresses Hepatic Fibrosis Via Targeting the hsa-miR-1291/LEFTY2 Axis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.741151 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ya-Ru Yang ◽

Shuang Hu ◽

Fang-Tian Bu ◽

Hao Li ◽

Cheng Huang ◽

...

Keyword(s):

Hepatic Fibrosis ◽

Circular Rna ◽

Vehicle Group ◽

Potential Biomarker ◽

Function Loss ◽

And Function ◽

Pro Inflammatory Cytokines

CircRNAs (circRNAs) are commonly dysregulated in a variety of human diseases and are involved in the development and progression of cancer. However, the role of circRNAs in hepatic fibrosis (HF) is still unclear. Our previous high throughput screen revealed changes in many circRNAs in mice with carbon tetrachloride (CCl4)-induced HF. For example, circCREBBP was significantly down-regulated in primary hepatic stellate cells (HSCs) and liver tissue of HF mice induced by CCl4 compared to those in the vehicle group. Overexpression of circCREBBP with AAV8-circCREBBP in vivo prevented CCl4-induced HF worsening by reducing serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) contents, liver hydroxyproline levels, collagen deposition, and levels of pro-fibrosis genes and pro-inflammatory cytokines. Furthermore, in vitro function loss and function gain analysis showed that circCREBBP inhibited HSCs activation and proliferation. Mechanically, circCREBBP acts as a sponge for hsa-miR-1291 and subsequently promotes LEFTY2 expression. In conclusion, our current results reveal a novel mechanism by which circCREBBP alleviates liver fibrosis by targeting the hsa-miR-1291/LEFTY2 axis, and also suggest that circCREBBP may be a potential biomarker for heart failure.

Download Full-text

A novel RLIM/RNF12 variant disrupts protein stability and function to cause severe Tonne-Kalscheuer syndrome

10.1101/2020.12.09.417873 ◽

2020 ◽

Author(s):

Francisco Bustos ◽

Carmen Espejo-Serrano ◽

Anna Segarra-Fas ◽

Alison J. Eaton ◽

Kristin D. Kernohan ◽

...

Keyword(s):

X Chromosome ◽

Ubiquitin Ligase ◽

Diaphragmatic Hernia ◽

E3 Ubiquitin Ligase ◽

Embryonic Stem ◽

Missense Variant ◽

X Chromosome Inactivation ◽

Severe Form ◽

Chromosome Inactivation ◽

And Function

ABSTRACTTonne-Kalscheuer syndrome (TOKAS) is an X-linked intellectual disability syndrome associated with variable clinical features including craniofacial abnormalities, hypogenitalism and diaphragmatic hernia. TOKAS is caused exclusively by variants in the gene encoding the E3 ubiquitin ligase gene RLIM, also known as. Here we report identification of a novel RLIM missense variant, c.1262A>G p.(Tyr421Cys) adjacent to the regulatory basic region, which causes a severe form of TOKAS resulting in perinatal lethality by diaphragmatic hernia. Inheritance and X-chromosome inactivation patterns implicate RLIM p.(Tyr421Cys) as the likely pathogenic variant in the affected individual and within the kindred. We show that the RLIM p.(Tyr421Cys) variant disrupts both expression and function of the protein in an embryonic stem cell model. RLIM p.(Tyr421Cys) is correctly localised to the nucleus, but is readily degraded by the proteasome. The RLIM p.(Tyr421Cys) variant also displays significantly impaired E3 ubiquitin ligase activity, which interferes with RLIM function in Xist long-non-coding RNA induction that initiates imprinted X-chromosome inactivation. Our data uncover a highly disruptive missense variant in RLIM that causes a severe form of TOKAS, thereby expanding our understanding of the molecular and phenotypic spectrum of disease severity.

Download Full-text