Evolution of Placental Function in Mammals: The Molecular Basis of Gas and Nutrient Transfer, Hormone Secretion, and Immune Responses

2012 ◽  
Vol 92 (4) ◽  
pp. 1543-1576 ◽  
Author(s):  
Anthony M. Carter
Keyword(s):  
Gene Duplication ◽  
Convergent Evolution ◽  
Globin Gene ◽  
Hormone Secretion ◽  
Human Leukocyte ◽  
Amino Acid Transporters ◽  
Placental Lactogens ◽  
Wide Range ◽  
Duplication Events ◽  
Range Of Functions

Placenta has a wide range of functions. Some are supported by novel genes that have evolved following gene duplication events while others require acquisition of gene expression by the trophoblast. Although not expressed in the placenta, high-affinity fetal hemoglobins play a key role in placental gas exchange. They evolved following duplications within the beta-globin gene family with convergent evolution occurring in ruminants and primates. In primates there was also an interesting rearrangement of a cassette of genes in relation to an upstream locus control region. Substrate transfer from mother to fetus is maintained by expression of classic sugar and amino acid transporters at the trophoblast microvillous and basal membranes. In contrast, placental peptide hormones have arisen largely by gene duplication, yielding for example chorionic gonadotropins from the luteinizing hormone gene and placental lactogens from the growth hormone and prolactin genes. There has been a remarkable degree of convergent evolution with placental lactogens emerging separately in the ruminant, rodent, and primate lineages and chorionic gonadotropins evolving separately in equids and higher primates. Finally, coevolution in the primate lineage of killer immunoglobulin-like receptors and human leukocyte antigens can be linked to the deep invasion of the uterus by trophoblast that is a characteristic feature of human placentation.

scholarly journals Convergent Biochemical Pathways for Xanthine Alkaloid Production in Plants Evolved from Ancestral Enzymes with Different Catalytic Properties

2021 ◽  
Author(s):  
Andrew J O’Donnell ◽  
Ruiqi Huang ◽  
Jessica J Barboline ◽  
Todd J Barkman
Keyword(s):  
Gene Duplication ◽  
Convergent Evolution ◽  
Catalytic Properties ◽  
Product Formation ◽  
Flowering Plants ◽  
Biochemical Pathways ◽  
Antecedent Conditions ◽  
Caffeine Synthase ◽  
Substrate Preferences ◽  
Duplication Events

Abstract Convergent evolution is widespread but the extent to which common ancestral conditions are necessary to facilitate the independent acquisition of similar traits remains unclear. In order to better understand how ancestral biosynthetic catalytic capabilities might lead to convergent evolution of similar modern-day biochemical pathways, we resurrected ancient enzymes of the caffeine synthase (CS) methyltransferases that are responsible for theobromine and caffeine production in flowering plants. Ancestral CS enzymes of Theobroma, Paullinia, and Camellia exhibited similar substrate preferences but these resulted in the formation of different sets of products. From these ancestral enzymes, descendants with similar substrate preference and product formation independently evolved after gene duplication events in Theobroma and Paullinia. Thus, it appears that the convergent modern-day pathways likely originated from ancestral pathways with different inferred flux. Subsequently, the modern-day enzymes originated independently via gene duplication and their convergent catalytic characteristics evolved to partition the multiple ancestral activities by different mutations that occurred in homologous regions of the ancestral proteins. These results show that even when modern-day pathways and recruited genes are similar, the antecedent conditions may be distinctive such that different evolutionary steps are required to generate convergence.

Structure, Function and Interactions of Tau: Particular Focus on Potential Drug Targets for the Treatment of Tauopathies

2018 ◽  
Vol 17 (5) ◽  
pp. 325-337 ◽  
Author(s):  
Hojjat Borna ◽  
Kasim Assadoulahei ◽  
Gholamhossein Riazi ◽  
Asghar Beigi Harchegani ◽  
Alireza Shahriary
Keyword(s):  
Tau Protein ◽  
Drug Targets ◽  
Brain Injuries ◽  
Potential Drug ◽  
Microtubule Network ◽  
Wide Range ◽  
Potential Risk Factors ◽  
Range Of Functions ◽  
Potential Drug Targets

Background & Objective: Neurodegenrative diseases are among the most widespread lifethreatening disorders around the world in elderly ages. The common feature of a group of neurodegenerative disorders, called tauopathies, is an accumulation of microtubule associated protein tau inside the neurons. The exact mechanism underlying tauopathies is not well-understood but several factors such as traumatic brain injuries and genetics are considered as potential risk factors. Although tau protein is well-known for its key role in stabilizing and organization of axonal microtubule network, it bears a broad range of functions including DNA protection and participation in signaling pathways. Moreover, the flexible unfolded structure of tau facilitates modification of tau by a wide range of intracellular enzymes which in turn broadens tau function and interaction spectrum. The distinctive properties of tau protein concomitant with the crucial role of tau interaction partners in the progression of neurodegeneration suggest tau and its binding partners as potential drug targets for the treatment of neurodegenerative diseases. Conclusion: This review aims to give a detailed description of structure, functions and interactions of tau protein in order to provide insight into potential therapeutic targets for treatment of tauopathies.

scholarly journals Role of Thioredoxin-Interacting Protein in Diseases and Its Therapeutic Outlook

2021 ◽  
Vol 22 (5) ◽  
pp. 2754
Author(s):  
Naila Qayyum ◽  
Muhammad Haseeb ◽  
Moon Suk Kim ◽  
Sangdun Choi
Keyword(s):  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Signaling Complex ◽  
Current Review ◽  
Wide Range ◽  
Range Of Functions ◽  
Species Production ◽  
And Oxidative Stress ◽  
Significant Attention

Thioredoxin-interacting protein (TXNIP), widely known as thioredoxin-binding protein 2 (TBP2), is a major binding mediator in the thioredoxin (TXN) antioxidant system, which involves a reduction-oxidation (redox) signaling complex and is pivotal for the pathophysiology of some diseases. TXNIP increases reactive oxygen species production and oxidative stress and thereby contributes to apoptosis. Recent studies indicate an evolving role of TXNIP in the pathogenesis of complex diseases such as metabolic disorders, neurological disorders, and inflammatory illnesses. In addition, TXNIP has gained significant attention due to its wide range of functions in energy metabolism, insulin sensitivity, improved insulin secretion, and also in the regulation of glucose and tumor suppressor activities in various cancers. This review aims to highlight the roles of TXNIP in the field of diabetology, neurodegenerative diseases, and inflammation. TXNIP is found to be a promising novel therapeutic target in the current review, not only in the aforementioned diseases but also in prolonged microvascular and macrovascular diseases. Therefore, TXNIP inhibitors hold promise for preventing the growing incidence of complications in relevant diseases.

scholarly journals The Role of HCN Channels on Membrane Excitability in the Nervous System

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Daisuke Kase ◽  
Keiji Imoto
Keyword(s):  
Intracellular Signaling ◽  
Hcn Channels ◽  
Heart Cells ◽  
Hcn Channel ◽  
Membrane Excitability ◽  
Wide Range ◽  
Inward Currents ◽  
Range Of Functions ◽  
Channel Currents

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels were first reported in heart cells and are recently known to be involved in a variety of neural functions in healthy and diseased brains. HCN channels generate inward currents when the membrane potential is hyperpolarized. Voltage dependence of HCN channels is regulated by intracellular signaling cascades, which contain cyclic AMP, PIP2, and TRIP8b. In addition, voltage-gated potassium channels have a strong influence on HCN channel activity. Because of these funny features, HCN channel currents, previously called funny currents, can have a wide range of functions that are determined by a delicate balance of modulatory factors. These multifaceted features also make it difficult to predict and elucidate the functional role of HCN channels in actual neurons. In this paper, we focus on the impacts of HCN channels on neural activity. The functions of HCN channels reported previously will be summarized, and their mechanisms will be explained by using numerical simulation of simplified model neurons.

scholarly journals Secondary Structure Libraries for Artificial Evolution Experiments

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1671
Author(s):  
Ráchel Sgallová ◽  
Edward A. Curtis
Keyword(s):  
Secondary Structure ◽  
Sequence Space ◽  
In Vitro Selection ◽  
Random Sequence ◽  
Random Mutagenesis ◽  
Nucleotide Composition ◽  
Artificial Evolution ◽  
Wide Range ◽  
Range Of Functions

Methods of artificial evolution such as SELEX and in vitro selection have made it possible to isolate RNA and DNA motifs with a wide range of functions from large random sequence libraries. Once the primary sequence of a functional motif is known, the sequence space around it can be comprehensively explored using a combination of random mutagenesis and selection. However, methods to explore the sequence space of a secondary structure are not as well characterized. Here we address this question by describing a method to construct libraries in a single synthesis which are enriched for sequences with the potential to form a specific secondary structure, such as that of an aptamer, ribozyme, or deoxyribozyme. Although interactions such as base pairs cannot be encoded in a library using conventional DNA synthesizers, it is possible to modulate the probability that two positions will have the potential to pair by biasing the nucleotide composition at these positions. Here we show how to maximize this probability for each of the possible ways to encode a pair (in this study defined as A-U or U-A or C-G or G-C or G.U or U.G). We then use these optimized coding schemes to calculate the number of different variants of model stems and secondary structures expected to occur in a library for a series of structures in which the number of pairs and the extent of conservation of unpaired positions is systematically varied. Our calculations reveal a tradeoff between maximizing the probability of forming a pair and maximizing the number of possible variants of a desired secondary structure that can occur in the library. They also indicate that the optimal coding strategy for a library depends on the complexity of the motif being characterized. Because this approach provides a simple way to generate libraries enriched for sequences with the potential to form a specific secondary structure, we anticipate that it should be useful for the optimization and structural characterization of functional nucleic acid motifs.

Secretory Proteases of the Human Skin Microbiome

2021 ◽  
Author(s):  
Wisely Chua ◽  
Si En Poh ◽  
Hao Li
Keyword(s):  
Human Skin ◽  
Hydrolytic Enzymes ◽  
Microbial Interactions ◽  
Skin Microbiome ◽  
Protein Cleavage ◽  
Wide Range ◽  
Range Of Functions ◽  
Diverse Community ◽  
Secreted Proteases ◽  
Pathogenic Agents

The human skin is our outermost layer and serves as a protective barrier against external insults. Advances in next generation sequencing have enabled the discoveries of a rich and diverse community of microbes - bacteria, fungi and viruses that are residents of this surface. The genomes of these microbes also revealed the presence of many secretory enzymes. In particular, proteases which are hydrolytic enzymes capable of protein cleavage and degradation are of special interest in the skin environment which is enriched in proteins and lipids. In this minireview, we will focus on the roles of these skin-relevant microbial secreted proteases, both in terms of their widely studied roles as pathogenic agents in tissue invasion and host immune inactivation, and their recently discovered roles in inter-microbial interactions and modulation of virulence factors. From these studies, it has become apparent that while microbial proteases are capable of a wide range of functions, their expression is tightly regulated and highly responsive to the environments the microbes are in. With the introduction of new biochemical and bioinformatics tools to study protease functions, it will be important to understand the roles played by skin microbial secretory proteases in cutaneous health, especially the less studied commensal microbes with an emphasis on contextual relevance.

scholarly journals A Rare Case of Coexistence of Homozygous β-Thalassaemia and Glucose 6 Phosphate Dehydrogenase Deficiency

2020 ◽  
Author(s):  
Jitendar Mohan Khunger ◽  
Monika Gupta ◽  
Ankur Jain ◽  
Monica Khunger Malhotra
Keyword(s):  
Oxidative Stress ◽  
Blood Cells ◽  
G6pd Deficiency ◽  
Rare Case ◽  
Dehydrogenase Deficiency ◽  
Globin Gene ◽  
Genetic Abnormality ◽  
Wide Range ◽  
Symptomatic Anaemia ◽  
Glucose 6 Phosphate Dehydrogenase

β-thalassaemia is one of the most prevalent autosomal disorders worldwide. Mutations/deletions in globin gene underlie deficiencies in Haemoglobin (Hb) production, which can interfere with oxygen delivery by Hb, resulting in thalassaemias causing anaemias with a wide range of disease severity. Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is a genetic abnormality resulting in inadequate amount of G6PD in the Red Blood Cells (RBCs). In patients with G6PD deficiency, the reduced or absent activity of the enzyme in RBCs causes premature haemolysis and symptomatic anaemia. The marked oxidative stress caused by homozygous β-thalassaemia is apparently incompatible with G6PD deficiency. Here, a rare case of six-month-old male child is described who presented with severe pallor hepato-splenomegaly and these two conditions co-existed in this patient.

scholarly journals Ultrabithorax Is a Micromanager of Hindwing Identity in Butterflies and Moths

2021 ◽  
Vol 9 ◽  
Author(s):  
Amruta Tendolkar ◽  
Aaron F. Pomerantz ◽  
Christa Heryanto ◽  
Paul D. Shirk ◽  
Nipam H. Patel ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Targeted Mutagenesis ◽  
Junonia Coenia ◽  
Wing Venation ◽  
Loss Of Function ◽  
Color Patterns ◽  
Wide Range ◽  
Range Of Functions ◽  
Gene Regulatory ◽  
Pyralid Moth

The forewings and hindwings of butterflies and moths (Lepidoptera) are differentiated from each other, with segment-specific morphologies and color patterns that mediate a wide range of functions in flight, signaling, and protection. The Hox gene Ultrabithorax (Ubx) is a master selector gene that differentiates metathoracic from mesothoracic identities across winged insects, and previous work has shown this role extends to at least some of the color patterns from the butterfly hindwing. Here we used CRISPR targeted mutagenesis to generate Ubx loss-of-function somatic mutations in two nymphalid butterflies (Junonia coenia, Vanessa cardui) and a pyralid moth (Plodia interpunctella). The resulting mosaic clones yielded hindwing-to-forewing transformations, showing Ubx is necessary for specifying many aspects of hindwing-specific identities, including scale morphologies, color patterns, and wing venation and structure. These homeotic phenotypes showed cell-autonomous, sharp transitions between mutant and non-mutant scales, except for clones that encroached into the border ocelli (eyespots) and resulted in composite and non-autonomous effects on eyespot ring determination. In the pyralid moth, homeotic clones converted the folding and depigmented hindwing into rigid and pigmented composites, affected the wing-coupling frenulum, and induced ectopic scent-scales in male androconia. These data confirm Ubx is a master selector of lepidopteran hindwing identity and suggest it acts on many gene regulatory networks involved in wing development and patterning.

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