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Topic Review
The HD-Domain Metalloprotein Superfamily
The histidine–aspartate (HD)-domain protein superfamily contains metalloproteins that share common structural features but catalyze vastly different reactions ranging from oxygenation to hydrolysis. This chemical diversion is afforded by (i) their ability to coordinate most biologically relevant transition metals in mono-, di-, and trinuclear configurations, (ii) sequence insertions or the addition of supernumerary ligands to their active sites, (iii) auxiliary substrate specificity residues vicinal to the catalytic site, (iv) additional protein domains that allosterically regulate their activities or have catalytic and sensory roles, and (v) their ability to work with protein partners. More than 500 structures of HD-domain proteins are available to date that lay out unique structural features which may be indicative of function. In this respect, we describe the three known classes of HD-domain proteins (hydrolases, oxygenases, and lyases) and identify their apparent traits with the aim to portray differences in the molecular details responsible for their functional divergence and reconcile existing notions that will help assign functions to yet-to-be characterized proteins.
  • 1.3K
  • 29 Oct 2020
Topic Review
The Hallmarks of Atrial Fibrillation
Atrial fibrillation (AF) is a prevalent cardiac condition predominantly affecting older adults, characterized by irregular heartbeat rhythm. The condition often leads to significant disability and increased mortality rates. 
  • 409
  • 24 Aug 2023
Topic Review
The H+ Transporter SLC4A11
Solute-linked cotransporter, SLC4A11, a member of the bicarbonate transporter family, is an electrogenic H+ transporter activated by NH3 and alkaline pH. Although SLC4A11 does not transport bicarbonate, it shares many properties with other members of the SLC4 family. SLC4A11 mutations can lead to corneal endothelial dystrophy and hearing deficits that are recapitulated in SLC4A11 knock-out mice. SLC4A11, at the inner mitochondrial membrane, facilitates glutamine catabolism and suppresses the production of mitochondrial superoxide by providing ammonia-sensitive H+ uncoupling that reduces glutamine-driven mitochondrial membrane potential hyperpolarization. Mitochondrial oxidative stress in SLC4A11 KO also triggers dysfunctional autophagy and lysosomes, as well as ER stress. SLC4A11 expression is induced by oxidative stress through the transcription factor NRF2, the master regulator of antioxidant genes.
  • 490
  • 25 Jan 2022
Topic Review
The Gut–Liver–Brain Axis
The gut–liver–brain axis constitutes a multidirectional communication network that connects the enteric, hepatic, and central nervous systems. Through the complex interplay between the gut–liver, gut–brain, and liver–brain axes, this communication network extends to involve endocrine, immune (humoral), and metabolic routes of communication. Within the network, the gut and liver affect cognitive behaviors through the host’s immune responses and the regulation of microbiota, and the brain also influences intestinal and hepatic activities. Studies in animals have shown that an impaired gut–liver–brain axis is associated with diseases such as hepatic encephalopathy, Alzheimer’s disease, Parkinson’s disease, Multiple Sclerosis, depression, and autism spectrum disorder (ASD).
  • 395
  • 01 Feb 2024
Topic Review
The Gut–Liver Axis of Boar Taint
The gut microbiome is a complex organ that is typically comprised of a couple hundred bacterial species expressing nearly 2 million different genes, which promote the biotransformation of xenobiotics and endogenous compounds and regulate the production of microbial metabolites in response to dietary, genetic, and environmental factors. Microbiota-derived compounds function as signaling molecules between different bacterial species to synchronize bacterial behaviours by altering the microbial population or the gene expression within the gut microbiome, which is known as quorum sensing. Gut-derived compounds also modulate metabolic pathways in the liver and intestines and act as ligands for nuclear receptors and other xenobiotic sensing transcription factors. In response, the liver produces bile to provide feedback to the gut microbiota and regulate further metabolite production. This bidirectional communication between the liver and the gut is referred to as the gut–liver axis and represents an important link between the gut microbiome and nuclear receptor signaling pathways.
  • 374
  • 13 Sep 2022
Topic Review
The Gut–Brain Axis within the Human Body
The human gut microbiota (GM) is a complex microbial ecosystem that colonises the gastrointestinal tract (GIT) and is comprised of bacteria, viruses, fungi, and protozoa. The GM has a symbiotic relationship with its host that is fundamental for body homeostasis. The GM is not limited to the scope of the GIT, but there are bidirectional interactions between the GM and other organs, highlighting the concept of the “gut–organ axis”. Any deviation from the normal composition of the GM, termed ”microbial dysbiosis”, is implicated in the pathogenesis of various diseases. Only a few studies have demonstrated a relationship between GM modifications and disease phenotypes, and it is still unknown whether an altered GM contributes to a disease or simply reflects its status. Restoration of the GM with probiotics and prebiotics has been postulated, but evidence for the effects of prebiotics is limited. Prebiotics are substrates that are “selectively utilized by host microorganisms, conferring a health benefit”.
  • 249
  • 19 Oct 2023
Topic Review
The Gut–Brain Axis
The gut–brain axis (GBA) it is a complex network in which the CNS and the enteric nervous system (ENS) interact with each other in a bilateral manner by several mechanisms, including nervous, hormonal, metabolic, and immunological ones. Recently, this relationship has been described as the ‘microbiota–gut–brain axis’ because of the known role of the gut microbiota in maintaining a physiological brain–gut relationship and its participation in the pathogenesis of several diseases. In this complex network, a plethora of interactions take place.
  • 843
  • 15 Sep 2021
Topic Review
The Gut Microbiota of Ruminant Animal
The microorganisms inhabiting the gastrointestinal tract (GIT) of ruminants have a mutualistic relationship with the host that influences the efficiency and health of the ruminants. 
  • 470
  • 25 Jul 2022
Topic Review
The Gut Microbiota Function
The microbiota is known as the set of microorganisms residing in each ecosystem, with a symbiotic relationship and with adaptive properties and rapid renewal, forming a large metabolic unit. The intestinal microbiota is a set of microorganisms made up of approximately 100,000 million bacteria that live in people intestine. The microbiota is responsible, among other functions, for maintaining the well-being of the intestinal mucosa, helping digest food and converting harmful elements into less toxic substances.
  • 431
  • 17 Oct 2022
Topic Review
The Gut Microbiota and Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular disease characterized by increased pulmonary vascular resistance, pulmonary vasoconstriction, and right ventricular hypertrophy. Developments in genomics and metabolomics have gradually revealed the roles of the gut microbiota (GM) and its metabolites in cardiovascular diseases. Accumulating evidence reveals that the GM plays important roles in the occurrence and development of PAH. Gut microbiota dysbiosis directly increases the gut permeability, thereby facilitating pathological bacterial translocation and allowing translocation of bacterial products such as lipopolysaccharides from the gut into circulation. This process aggravates pulmonary perivascular inflammation and exacerbates PAH development through the endothelial–mesenchymal transition. Additionally, a shift in the composition of PAH also affects the gut metabolites. Changes in gut metabolites, such as decreased short-chain fatty acids, increased trimethylamine N-oxide, and elevated serotonin, contribute to pulmonary perivascular inflammation and pulmonary vascular remodeling by activating several signaling pathways. Studies of the intestinal microbiota in treating pulmonary hypertension have strengthened linkages between the GM and PAH. Probiotic therapy and fecal microbiota transplantation may supplement existing PAH treatments.
  • 593
  • 04 Nov 2022
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