scholarly journals Conserved UBE3A subcellular distribution between human and mice is facilitated by non-homologous isoforms

2020 ◽  
Vol 29 (18) ◽  
pp. 3032-3043
Author(s):  
F Isabella Zampeta ◽  
Monica Sonzogni ◽  
Eva Niggl ◽  
Bas Lendemeijer ◽  
Hilde Smeenk ◽  
...  
Keyword(s):  
Amino Acid ◽  
Subcellular Distribution ◽  
Protein Isoforms ◽  
Single Amino Acid ◽  
New World Monkeys ◽  
Old World Monkeys ◽  
Amino Acid Deletion ◽  
Old World ◽  
Ubiquitin E3 Ligase ◽  
Human Neurons

Abstract The human UBE3A gene, which is essential for normal neurodevelopment, encodes three Ubiquitin E3 ligase A (UBE3A) protein isoforms. However, the subcellular localization and relative abundance of these human UBE3A isoforms are unknown. We found, as previously reported in mice, that UBE3A is predominantly nuclear in human neurons. However, this conserved subcellular distribution is achieved by strikingly distinct cis-acting mechanisms. A single amino-acid deletion in the N-terminus of human hUBE3A-Iso3, which is homologous to cytosolic mouse mUBE3A-Iso2, results in its translocation to the nucleus. This singe amino-acid deletion is shared with apes and Old World monkeys and was preceded by the appearance of the cytosolic hUBE3A-Iso2 isoform. This hUBE3A-Iso2 isoform arose after the lineage of New World monkeys and Old World monkeys separated from the Tarsiers (Tarsiidae). Due to the loss of a single nucleotide in a non-coding exon, this exon became in frame with the remainder of the UBE3A protein. RNA-seq analysis of human brain samples showed that the human UBE3A isoforms arise by alternative splicing. Consistent with the predominant nuclear enrichment of UBE3A in human neurons, the two nuclear-localized isoforms, hUBE3A-Iso1 and -Iso3, are the most abundantly expressed isoforms of UBE3A, while hUBE3A-Iso2 maintains a small pool of cytosolic UBE3A. Our findings provide new insight into UBE3A localization and evolution and may have important implications for gene therapy approaches in Angelman syndrome.

“Tho' she kneel'd in that place where they grew…” The uses and origins of primate colour vision

1989 ◽  
Vol 146 (1) ◽  
pp. 21-38 ◽  
Author(s):  
J. D. Mollon
Keyword(s):  
X Chromosome ◽  
Colour Vision ◽  
Visual Pathway ◽  
New World Monkeys ◽  
Old World Monkeys ◽  
Old World ◽  
Early Stages ◽  
Local Sign ◽  
Retinal Photoreceptor ◽  
Recent Duplication

The disabilities experienced by colour-blind people show us the biological advantages of colour vision in detecting targets, in segregating the visual field and in identifying particular objects or states. Human dichromats have especial difficulty in detecting coloured fruit against dappled foliage that varies randomly in luminosity; it is suggested that yellow and orange tropical fruits have co-evolved with the trichromatic colour vision of Old World monkeys. It is argued that the colour vision of man and of the Old World monkeys depends on two subsystems that remain parallel and independent at early stages of the visual pathway. The primordial subsystem, which is shared with most mammals, depends on a comparison of the rates of quantum catch in the short- and middle-wave cones; this system exists almost exclusively for colour vision, although the chromatic signals carry with them a local sign that allows them to sustain several of the functions of spatiochromatic vision. The second subsystem arose from the phylogenetically recent duplication of a gene on the X-chromosome, and depends on a comparison of the rates of quantum catch in the long- and middle-wave receptors. At the early stages of the visual pathway, this chromatic information is carried by a channel that is also sensitive to spatial contrast. The New World monkeys have taken a different route to trichromacy: in species that are basically dichromatic, heterozygous females gain trichromacy as a result of X-chromosome inactivation, which ensures that different photopigments are expressed in two subsets of retinal photoreceptor.

scholarly journals Pulmonary granuloma is not always the tuberculosis hallmark: pathological findings of different tuberculosis stages in New and Old World Nonhuman Primates naturally infected with the Mycobacterium tuberculosis Complex

2021 ◽  
Author(s):  
Asheley H. B. Pereira ◽  
Claudia A. A. Lopes ◽  
Thalita A. Pissinatti ◽  
Ana C. A. Pinto ◽  
Daniel R. A. Oliveira ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
New World ◽  
Nonhuman Primates ◽  
World Monkey ◽  
Histological Evaluation ◽  
New World Monkeys ◽  
Old World Monkeys ◽  
Pathological Findings ◽  
Old World ◽  
Pulmonary Granuloma

Abstract Herein we present the pathological findings of different tuberculosis stages in Old and New World monkeys kept under human care in Rio de Janeiro, Brazil and naturally infected with Mycobacterium tuberculosis Complex. Fifteen nonhuman primates from five different colonies were incorporated into the study. There are 60% (9/15) Old World Monkeys and 40% (6/15) New World Monkeys. According to the gross and histopathologic findings, the lesions in nonhuman primates of this study are classified into the chronic-active, extrapulmonary, early-activation or latent-reactivation tuberculosis stage. Among the Old World Monkey, 66.7% (6/9) of nonhuman primates, all rhesus monkeys (Macaca mulatta), showed severe granulomatous pneumonia. In all Old World Monkeys cases, typical granulomas were seen in at least one organ regardless of the stage of the disease. In the New World Monkeys, the typical pulmonary granulomas were seen in 16.7% (1/6) of the cases, just in the latent-reactivation stage in Uta Hick’s Bearded Saki (Chiropotes utahickae). In this study, 66.7% (6/9) of Old World Monkeys (OWM) and 83.3% (5/6) of New World Monkeys (NWM) showed pulmonary changes at the histological evaluation. The tuberculosis diagnosis in the nonhuman primates in this study was based on pathological, immunohistochemical, molecular, and bacteriological culture. Although the typical presentation was observed in some cases, the absence of pulmonary granuloma did not exclude the tuberculosis occurrence in nonhuman primates of the Old and New World. Tuberculosis should be included as a cause of interstitial pneumonia with foamy macrophages infiltration in the New World nonhuman primates. Due to the high sensitivity of immunohistochemistry with Anti-Mycobacterium tuberculosis, we suggest the addition of this technique as a diagnostic tool of tuberculosis in the nonhuman primates even when the typical changes are not seen.

Pfeiffer syndrome type 2 associated with a single amino acid deletion in the PGFR2 gene

2000 ◽  
Vol 58 (1) ◽  
pp. 81-83 ◽  
Author(s):  
Manuela Priolo ◽  
Margherita Lerone ◽  
Maria Baffico ◽  
Maurizia Baldi ◽  
Roberto Ravazzolo ◽  
...  
Keyword(s):  
Amino Acid ◽  
Single Amino Acid ◽  
Syndrome Type ◽  
Amino Acid Deletion ◽  
Pfeiffer Syndrome

scholarly journals Species differences in the aromatization of quinic acid in vivo and the role of gut bacteria

1970 ◽  
Vol 116 (3) ◽  
pp. 437-443 ◽  
Author(s):  
R. H. Adamson ◽  
J. W. Bridges ◽  
M. E. Evans ◽  
R. T. Williams
Keyword(s):  
Rhesus Monkey ◽  
Rhesus Monkeys ◽  
Hippuric Acid ◽  
Shikimic Acid ◽  
Tree Shrew ◽  
Quinic Acid ◽  
New World Monkeys ◽  
Old World Monkeys ◽  
Gut Flora ◽  
Old World

1. The fate of (-)-quinic acid has been investigated in 22 species of animals including man. 2. In man and three species of Old World monkeys, i.e. rhesus monkey, baboon and green monkey, oral quinic acid was extensively aromatized (20–60%) and excreted in the urine as hippuric acid, which was determined fluorimetrically. 3. In three species of New World monkeys, i.e. squirrel monkey, spider monkey and capuchin, in three species of lemurs, i.e. bushbaby, slow loris and tree shrew, in the dog, cat, ferret, rabbit, rat, mouse, guinea pig, hamster, lemming, fruit bat, hedgehog and pigeon, oral quinic acid was not extensively aromatized (0–5%). 4. In the rhesus monkey, injected quinic acid was not aromatized, but largely excreted unchanged. 5. In rhesus monkeys pretreated with neomycin to suppress gut flora, the aromatization of oral quinic acid was considerably suppressed. 6. In rats and rhesus monkeys [14C]quinic acid was used and this confirmed its low aromatization in rats and its high aromatization in the monkeys. 7. Shikimic acid given orally was excreted as hippuric acid (26–56%) in rhesus monkeys, but not in rats. 8. The results support the view that quinic acid and shikimic acid are aromatized by the gut flora in man and the Old World monkeys.

scholarly journals Reflexive gaze following in common marmoset monkeys

2019 ◽  
Author(s):  
Silvia Spadacenta ◽  
Peter W. Dicke ◽  
Peter Thier
Keyword(s):  
Joint Attention ◽  
World Monkey ◽  
Common Marmoset ◽  
Gaze Following ◽  
New World Monkeys ◽  
List Type ◽  
Old World Monkeys ◽  
Common Marmosets ◽  
Old World ◽  
Domain Specific

ABSTRACTThe ability to extract the direction of the other’s gaze allows us to shift our attention to an object of interest to the other and to establish joint attention. By mapping one’s own expectations, desires and intentions on the object of joint attention, humans develop a Theory of (the other’s) Mind (TOM), a functional sequence possibly disrupted in autism. Although old world monkeys probably do not possess a TOM, they follow the other’s gaze and they establish joint attention. Gaze following of both humans and old world monkeys fulfills Fodor’s criteria of a domain specific function and is orchestrated by very similar cortical architectures, strongly suggesting homology. Also new world monkeys, a primate suborder that split from the old world monkey line about 35 million years ago, have complex social structures. One member of this group, the common marmoset (Callithrix jacchus), has received increasing interest as a potential model in studies of normal and disturbed human social cognition. Marmosets are known to follow human head-gaze. However, the question is if they use gaze following to establish joint attention with conspecifics. Here we show that this is indeed the case. In a free choice task, head-restrained marmosets prefer objects gazed at by a conspecific and, moreover, they exhibit considerably shorter choice reaction times for the same objects. These findings support the assumption of an evolutionary old domain specific faculty shared within the primate order and they underline the potential value of marmosets in studies of normal and disturbed joint attention.HIGHLIGHTSCommon marmosets follow the head gaze of conspecifics in order to establish joint attention.Brief exposures to head gaze are sufficient to reallocate an animal’s attention.The tendency to follow the other’s gaze competes with the attractional binding of the conspecific’s face

scholarly journals Computational prediction of the tolerance to amino-acid deletion in green-fluorescent protein

2016 ◽  
Author(s):  
Eleisha L. Jackson ◽  
Stephanie J. Spielman ◽  
Claus O. Wilke
Keyword(s):  
Green Fluorescent Protein ◽  
Protein Structure ◽  
Amino Acid ◽  
Protein Design ◽  
Fluorescent Protein ◽  
Computational Prediction ◽  
Single Amino Acid ◽  
Dimensional Structure ◽  
Amino Acid Deletion ◽  
Green Fluorescent

AbstractProteins evolve through two primary mechanisms: substitution, where mutations alter a protein’s amino-acid sequence, and insertions and deletions (indels), where amino acids are either added to or removed from the sequence. Protein structure has been shown to influence the rate at which substitutions accumulate across sites in proteins, but whether structure similarly constrains the occurrence of indels has not been rigorously studied. Here, we investigate the extent to which structural properties known to covary with protein evolutionary rates might also predict protein tolerance to indels. Specifically, we analyze a publicly available dataset of single–amino-acid deletion mutations in enhanced green fluorescent protein (eGFP) to assess how well the functional effect of deletions can be predicted from protein structure. We find that weighted contact number (WCN), which measures how densely packed a residue is within the protein’s three-dimensional structure, provides the best single predictor for whether eGFP will tolerate a given deletion. We additionally find that using protein design to explicitly model deletions results in improved predictions of functional status when combined with other structural predictors. Our work suggests that structure plays fundamental role in constraining deletions at sites in proteins, and further that similar biophysical constraints influence both substitutions and deletions. This study therefore provides a solid foundation for future work to examine how protein structure influences tolerance of more complex indel events, such as insertions or large deletions.

scholarly journals Human Natural Antibodies to Mammalian Carbohydrate Antigens as Unsung Heroes Protecting against Past, Present, and Future Viral Infections

Antibodies ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 25 ◽  
Author(s):  
Uri Galili
Keyword(s):  
Blood Group ◽  
Viral Infections ◽  
Mammalian Species ◽  
Natural Antibodies ◽  
New World Monkeys ◽  
Old World Monkeys ◽  
Carbohydrate Antigens ◽  
Old World ◽  
Enveloped Virus ◽  
Zoonotic Viruses

Human natural antibodies to mammalian carbohydrate antigens (MCA) bind to carbohydrate-antigens synthesized in other mammalian species and protect against zoonotic virus infections. Three such anti-MCA antibodies are: (1) anti-Gal, also produced in Old-World monkeys and apes, binds to α-gal epitopes synthesized in non-primate mammals, lemurs, and New-World monkeys; (2) anti-Neu5Gc binds to Neu5Gc (N-glycolyl-neuraminic acid) synthesized in apes, Old-World monkeys, and many non-primate mammals; and (3) anti-Forssman binds to Forssman-antigen synthesized in various mammals. Anti-viral protection by anti-MCA antibodies is feasible because carbohydrate chains of virus envelopes are synthesized by host glycosylation machinery and thus are similar to those of their mammalian hosts. Analysis of MCA glycosyltransferase genes suggests that anti-Gal appeared in ancestral Old-World primates following catastrophic selection processes in which parental populations synthesizing α-gal epitopes were eliminated in enveloped virus epidemics. However, few mutated offspring in which the α1,3galactosyltransferase gene was accidentally inactivated produced natural anti-Gal that destroyed viruses presenting α-gal epitopes, thereby preventing extinction of mutated offspring. Similarly, few mutated hominin offspring that ceased to synthesize Neu5Gc produced anti-Neu5Gc, which destroyed viruses presenting Neu5Gc synthesized in parental hominin populations. A present-day example for few humans having mutations that prevent synthesis of a common carbohydrate antigen (produced in >99.99% of humans) is blood-group Bombay individuals with mutations inactivating H-transferase; thus, they cannot synthesize blood-group O (H-antigen) but produce anti-H antibody. Anti-MCA antibodies prevented past extinctions mediated by enveloped virus epidemics, presently protect against zoonotic-viruses, and may protect in future epidemics. Travelers to regions with endemic zoonotic viruses may benefit from vaccinations elevating protective anti-MCA antibody titers.

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