bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ageing Genes: Gerontogenes
Authors: Rattan Suresh IS 
Published: January 2018

Abstract

The idea of gerontogenes is in line with the evolutionary explanation of ageing as being an emergent phenomenon as a result of the imperfect maintenance and repair systems. Although evolutionary processes did not select for any specific ageing genes that restrict and determine the lifespan of an individual, the term ‘gerontogenes’ primarily refers to any genes that may seem to influence ageing and longevity, without being specifically selected for that role. Such genes can also be called ‘virtual gerontogenes’ by virtue of their indirect influence on the rate and process of ageing. More than 1000 virtual gerontogenes have been associated with ageing and longevity in model organisms and humans. The ‘real’ genes, which do influence the essential lifespan of a species, and have been selected for in accordance with the evolutionary life history of the species, are known as the longevity assurance genes.

Key Concepts

Biological ageing is a progressive decline in functional ability and an increase in the chances of frailty, diseases and death.

Ageing can be considered to set in mainly after the completion of the essential lifespan (ELS) of a species.

ELS is the duration of time required by a species in its natural environment in order to grow, develop, mature and reproduce.

Evolution has selected for longevity assurance genes (LAG) that determine ELS of a species.

Genetic pathways of maintenance and repair are the basis of LAG, and give rise to the homeodynamic space of an individual within a species.

Ageing is the progressive shrinkage of the homeodynamic space.

Evolution has not selected for any genes with the specific function of causing ageing and terminating the life of an individual.

Ageing, age‐related diseases and death are not programmed.

Genes for ageing – gerontogenes – is a conceptual term for discussing the involvement of genes in affecting the rate and extent of ageing.

Gerontogenes are not real; they are, at best, virtual in the sense that LAG become altered because of molecular damage and epigenetic alterations.

Hundreds of putative virtual gerontogenes have been associated with the longevity of model organisms and humans.

Eliminating ageing and death by gene therapy is at present only a wishful thinking.
Cytochrome
P450
(

CYP

) Gene Superfamily
Authors: Nelson David R , Nebert Daniel W 
Published: January 2018

Abstract

Cytochrome P450, named in the 1960s as a ‘chromatic (coloured) pigment in the cell’ having an absorption maximum of 450 nm when reduced and bound to carbon monoxide, was originally thought to be a single enzyme. P450 was correlated with drug and steroid metabolism; eventually, P450 was recognised to comprise an ancient gene superfamily encoding numerous ubiquitous enzymes that participate in countless essential life processes. Almost 55 000 P450 genes have now been named across all kingdoms of life. Nearly all eukaryotes require sterols in their membranes for essential fluidity and lipid‐packing properties; CYP51 (sterol 14α‐demethylase) synthesises these sterols and, therefore, is fundamental to eukaryotic life and most likely the ancestral P450 gene from which all others were derived. Cytochromes P450 evolved novel functions in chordates, leading to the beginning of steroid hormones. In conjunction with steroid hormone receptors, these novel regulatory pathways distinguish chordates from other animals. Among human's 57 functional CYP genes, DNA variants can cause a number of inborn errors of metabolism, other clinical diseases, and important differences in drug response.

Key Concepts

Cytochromes P450 (CYPs) are haem‐containing membrane proteins in the endoplasmic reticulum (ER) or mitochondrial inner membrane.

Most CYPs require a source of electrons from an electron transfer chain to function: NADPH‐cytochrome P450 oxidoreductase (POR) in ER and ferredoxin (FDX) plus ferredoxin reductase (FDXR) in mitochondria.

CYP functions can be divided into oxidation/reduction of endogenous compounds and foreign chemicals (e.g. drugs, environmental pollutants).

Endogenous P450 substrates include mostly lipids (steroids, lanosterol, bile acids, vitamin D, retinoic acid, eicosanoids and other lipid mediators), fatty acids and haem breakdown products.

As of 2017, at least six of 57 human P450s still remain ‘orphans’ without agreed‐upon identifiable substrates.

Cytochromes P450 in humans (and most vertebrates) are divided into 18 CYP gene families – based on amino acid sequence similarity.

CYP gene polymorphisms can alter a person's ability to metabolise drugs (poor, intermediate, efficient or ultrarapid metabolisers).

Human CYP3A4 and CYP2D6 are the two major drug‐metabolising enzymes. Removal of mouse
Cyp
genes and replacement with their human
CYP
orthologous genes will lead to a better understanding of P450 metabolism that is relevant to clinical pharmacology.

Alterations in CYP drug metabolism are often responsible for adverse drug reactions – especially when multiple drugs are taken.

Triazole antifungal drugs (ketoconazole, fluconazole and itraconazole) target the CYP51 required for fungal sterol biosynthesis; mutations in this gene can lead to triazole drug resistance.
Basepair (
bp
)
Authors: Dear Paul H 
Published: January 2018

Abstract

A basepair is a single subunit of double‐stranded nucleic acid, consisting of two nucleotides in opposite strands linked by hydrogen bonds. Only certain combinations of nucleotides can form base pairs, so the sequence of nucleotides in one strand is complementary to the sequence in the other. Base pairing is essential not just for maintaining the double‐helical structure of DNA but also for the replication of nucleic acids, for making an RNA copy of a DNA strand, and for repairing damage to DNA. So, while the sequence of nucleotides
within
a strand encodes information, it is base pairing
between
strands that allows nucleic acids to perform most of their functions. Base pairing also underpins many aspects of biotechnology, such as DNA sequencing.

Key Concepts

Base pairing is the formation of hydrogen bonds between the bases (subunits) of two strands of DNA or RNA.

Only certain combinations of bases (complementary pairs) can form basepairs.

When DNA is replicated, or when an RNA copy is made in a process called transcription, base pairing ensures that the new DNA or RNA strand is a mirror image, or complement, of the old strand.

When damaged DNA is repaired, base pairing is used to reconstruct a damaged strand using the undamaged strand as a template.

Base pairing is also exploited in many aspects of biotechnology, such as the polymerase chain reaction (PCR) and DNA sequencing.
Regulatory
B
Cells
Authors: Guzman‐Genuino Ruth Marian , Diener Kerrilyn R 
Published: January 2018

Abstract

B cells are best known for their ability to produce antibodies and instigate immune memory necessary for the protection of the host against foreign stimuli. However, certain subsets of B cells are increasingly shown to be capable of negative immune regulation by counteracting inflammation and suppressing the immune response. These cells are aptly termed ‘regulatory B cells’ or ‘Bregs’ and carry out their function by multiple mechanisms that include production of anti‐inflammatory cytokines and cognate interaction with other immune cells. Bregs are able to restore an immune response to homeostatic levels and as such play crucial roles in health conditions requiring suppression of inflammation and/or maintenance of tolerance such as in autoimmunity, graft tolerance, allergy, infection, cancer and pregnancy. Understanding how these potent and dynamic cells can be controlled in various immune situations offers a promising avenue for the development of novel prophylactic and immune therapy treatments.

Key Concepts

Regulatory B cells or Bregs are B‐cell subsets capable of downmodulating the immune response.

Bregs can suppress the immune response by producing anti‐inflammatory cytokines such as IL‐10 and TGF‐β, or through cell–cell contact with other immune cells.

Bregs can limit the severity and progression of autoimmune diseases such as multiple sclerosis, systemic lupus erythematosus and rheumatoid arthritis by recruiting regulatory T cells and inhibiting proinflammatory cytokine production by helper T cells.

Higher Breg frequency in peripheral circulation is correlated with operational tolerance in transplantation patients.

Bregs induce and promote allergen tolerance primarily through IL‐10 production.

Bregs can inhibit the immune response to viral, bacterial and parasitic infections, thereby allowing pathogen survival and disease progression.

Bregs in tumour sites can hinder effector immune cells from attacking and eliminating cancer cells.

In pregnancy, Bregs are likely to play an important role in the induction of maternal tolerance necessary for the successful growth of semiallogeneic foetus.
NOD‐Like Receptors
Authors: Arnold Christine , Kienes Ioannis , Sowa Anna S , Kufer Thomas A 
Published: January 2018

AbstractNOD‐like receptors (NLRs) are a family of pattern recognition receptors (PRRs), able to respond to conserved microbial structures and endogenous danger signals. NLRs modulate the inflammatory response via multiple pathways including NFκB (nuclear factor kappa‐light chain‐enhancer of activated B cells)‐activation, MAPKs, ERK and inflammasome formation, which results in IL‐1β release. They act in synergy with other PRRs, bridging innate to adaptive immunity. Moreover, some NLRs directly modulate adaptive immunity via transcriptional regulation of MHC (major histocompatibility complex) class I and class II. Their essential role in orchestrating inflammatory responses is seen via their association with morbidity. NLR dysfunction can result in cancer and autoinflammatory diseases, such as Crohn's disease and ulcerative colitis, pointing out their important role in maintaining gut homeostasis.Key ConceptsNLRs are an intracellular subclass of PRRs that recognise microbe‐associated molecular patterns (MAMPs) and danger‐associated molecular patterns (DAMPs).NLRs are found in different animal species and have homologues in plants.NLRs share a common tripartite structure, typically consisting of anN‐terminal domain from the death‐fold family, a central NACHT domain and a variable number ofC‐terminal LRRs.Activation of NLRs primes innate and adaptive immunity and drives the expression of MHC class I and class II genes.Some NLRs form inflammasomes, multiprotein platforms for caspase‐1 activation and IL‐1β release.NLRs maintain gut homeostasis, differentiating between commensals and pathogens.Mutations in NLRs can lead to severe autoinflammatory diseases, cancer, dysregulation of gut homeostasis and innate immune responses.Evidence suggests that some NLRs are further implicated in development.The function of some of the 22 human NLR proteins remains elusive.
Real‐Time Functional Magnetic Resonance Imaging
Authors: MacInnes Jeff J , Dickerson Kathryn C 
Published: January 2018

Abstract

Real‐time functional magnetic resonance imaging (rt‐fMRI) is an increasingly popular noninvasive technique used to study brain function in ‘real time’. In contrast to traditional fMRI, rt‐fMRI allows researchers to access and manipulate neuroimaging data as they are acquired. This advance allows experimenters to use fMRI data in novel ways, including: quality assessment, biofeedback, dynamically controlled experimental tasks and assistive technologies (e.g. control over prostheses). Cutting‐edge research in this field has demonstrated compelling findings in healthy human participants and patient populations alike, including: volitional regulation of multiple brain regions, improved symptoms in several clinical populations and successful nonverbal communication. As rt‐fMRI is still in the early phases of development, we anticipate that this technology will continue to be used in novel and exciting ways by current and future generations of scientists.

Key Concepts

Real‐time functional magnetic resonance imaging (rt‐fMRI) allows fMRI data to be analysed during data acquisition and provides a number of advantages over traditional fMRI.

Common uses of rt‐fMRI include data monitoring and quality control, neurofeedback training, dynamic task control and use as an assistive technology.

While first introduced in the late 1990s, the development and usage of rt‐fMRI have grown markedly in recent years.

Limitations and challenges of rt‐fMRI include determining effective control conditions, accounting for the lag in the BOLD signal and online data processing.

Rt‐fMRI is an exciting technique that promises to kindle both novel basic science and clinical research.
Celiac Disease: Molecular Basis
Authors: Picascia Stefania , Camarca Alessandra , Gianfrani Carmen 
Published: January 2018

Abstract

Celiac disease (CD) is an inflammatory and multifactorial disorder triggered by cereal gluten in genetically predisposed individuals. CD has several clinical and histological forms characterised by different grade of small intestinal inflammation. Several studies have demonstrated the key role of adaptive CD4+ T lymphocytes in gluten‐dependent enteropathy, although it has been clear that the intraepithelial CD8+ T lymphocytes of innate immunity, highly infiltrating CD mucosa, are pivotal in the induction of intestinal mucosa alteration and malfunction. Recent evidences also highlighted how adaptive CD8+ T lymphocytes restricted by HLA class I molecules contribute to the enterocytes damage through a TCR‐dependent cytotoxic activity. The recent findings on the involvement of HLA class I genes in CD susceptibility are also discussed.

Key Concepts

Celiac disease is an immune‐mediated disorder triggered by dietary gluten.

Enteropathy is the main form of celiac disease, but extra‐intestinal manifestations are also frequent.

Celiac disease has autoimmune features characterised by the production of antitissue transglutaminase antibodies, with high diagnostic relevance.

Gluten‐reactive CD4+ T cells are key players as pathogenic T helper cells.

Cytotoxic CD8+ T cells, of both innate and adaptive branches, are involved in the intestinal villous atrophy.

The current therapy is the avoidance of gluten from the diet.
5‐

HT
3

Receptors
Authors: Lummis Sarah 
Published: January 2018

Abstract

The 5‐HT
3
receptor is a cation‐selective member of the pentameric ligand‐gated ion channel (pLGIC) family. It differs both structurally and functionally from the other six classes of 5‐HT receptors, which are G‐protein coupled receptors. 5‐HT
3
receptors are pentamers, and five different subunits have been identified (5‐HT3A–E). These are widely distributed, both in the nervous system and in other tissues, although the stoichiometry of most functional heteromeric receptors is still not known. 5‐HT
3
receptor activation opens a nonselective cation channel, causing depolarisation in postsynaptic cells; receptor function can be modulated by a wide range of compounds including anaesthetics, opioids and alcohols. 5‐HT
3
receptors play a major role in the vomiting reflex, regulate gut motility, secretion and peristalsis in the enteric nervous system, and are involved in information transfer in the gastrointestinal tract. Disturbances within the 5‐HT
3
receptor system may contribute to the pathogenesis of a range of neurological, gastrointestinal and immunological disorders.

Key Concepts

5‐HT
3
receptors are members of the pentameric ligand‐gated ion channel family of neurotransmitter receptors.

5‐HT
3
receptors have a bullet‐shaped structure, with extracellular, transmembrane and intracellular domains.

5‐HT
3
receptor activation opens a cation channel resulting in cell depolarisation.

5‐HT
3
receptor function can be modulated by a wide range of compounds including anaesthetics, opioids and alcohols.

5‐HT
3
receptors are involved in the function of both the central and peripheral nervous systems, including specific roles in the vomiting reflex and in the gastrointestinal tract.

Disturbances within the 5‐HT
3
receptor system may contribute to the pathogenesis of a range of neurological, gastrointestinal and immunological disorders.

5‐HT
3
receptor antagonists are effective at treating nausea, emesis and irritable bowel syndrome, and have potential in a range of other disorders.
Translational potential of human brain organoids
Authors: Sun Alfred X. , Ng Huck‐Hui , Tan Eng‐King 
Published: January 2018

AbstractThe recent technology of 3D cultures of cellular aggregates derived from human stem cells have led to the emergence of tissue‐like structures of various organs including the brain. Brain organoids bear molecular and structural resemblance with developing human brains, and have been demonstrated to recapitulate several physiological and pathological functions of the brain. Here we provide an overview of the development of brain organoids for the clinical community, focusing on the current status of the field with an critical evaluation of its translational value.
Efficient, Selective, and Reversible SO2 Capture with Highly Crosslinked Ionic Microgels via a Selective Swelling Mechanism
Authors: Xia Ling , Cui Qing , Suo Xian , Li Yuhui , Cui Xili , Yang Qiwei , Xu Jianhong , Yang Yiwen , Xing Huabin 
Published: January 2018

AbstractSO2 capture through physisorption is a promising environmental benign technology to eliminate the emission of SO2. However, designing an efficient adsorption material with high capacity and selectivity of SO2 as well as excellent reversibility remains challenging. Here, a class of highly crosslinked nonporous poly(ionic liquid)s (PILs) xerogels is prepared with high ionic density by photopolymerization of Gemini IL monomers and a microfluidic technology is further explored to prepare the corresponding monodisperse PIL microgels with uniform and controllable sizes at the diameter range from 43 to 250 µm. This kind of novel dense nonporous ionic xerogels/microgels completely exclude the adsorption of common gases (CO2, CH4, etc.), but exhibit very high SO2 adsorption capacity (498 mg g−1) via selective swelling mechanism. Unprecedented SO2/CO2 and SO2/CH4 uptake selectivities with the value up to 614 and 1992, respectively, are achieved. The selective swelling mechanism is validated by optical microscope and differential scanning calorimetry measurements. More importantly, these kinds of xerogels show excellent reversibility in adsorption–desorption cycles. Column breakthrough experiments confirm the excellent performance of these PIL xerogels in SO2 capture. This work demonstrates that designing a nonporous material that has specific swelling interactions with certain molecules can be an effective strategy for realizing extremely high selectivity.
Engineering the Exciton Dissociation in Quantum‐Confined 2D CsPbBr3 Nanosheet Films
Authors: Yang Zhi , Wang Minqiang , Qiu Hengwei , Yao Xi , Lao Xiangzhou , Xu Shijie , Lin Zhonghai , Sun Luyi , Shao Jinyou 
Published: January 2018

AbstractRecent years have witnessed a rapid development of all‐inorganic halide perovskite in optoelectronic devices. Ultrathin 2D CsPbBr3 nanosheets (NSs) with large lateral dimensions have demonstrated exceptional photophysical properties because of their analogous exciton electronic structure to quantum wells. Despite the incredible progress on device performance, the photophysics and carrier transportation parameters of quantum‐confined CsPbBr3 NSs are lacking, and the fundamental understanding of the exciton dissociation mechanism is far less developed. Here, a ligands rearrangement mechanism is proposed to explain why annealed NS films have an increased charge transfer rate and a decreased exciton binding energy and lifetime, prompting tunneling as a dominant way of exciton dissociation to separate photogenerated excitons between neighboring NSs. This facile but efficient method provides a new insight to manipulate perovskite nanocrystals coupling. Moreover, ultrathin 2D CsPbBr3 NS film is demonstrated to have a enhanced absorption cross section and high carrier mobility of 77.9 cm2 V−1 s−1, contributing to its high responsivity of 0.53 A W−1. The photodetector has a long‐term stability up to three months, which are responsible for reliable perovskite‐based device performance.
Multifunctional Shell–Core Nanoparticles for Treatment of Multidrug Resistance Hepatocellular Carcinoma
Authors: Wang Qi , Zhang Xiangyu , Liao Hongze , Sun Ying , Ding Li , Teng Yanwei , Zhu Wei‐Hong , Zhang Zhirong , Duan Yourong 
Published: January 2018

AbstractMultidrug resistance (MDR) is the main obstruction against the chemotherapy for hepatocellular carcinoma. Herein, a biodegradable multifunctional tumor‐targeted core–shell structural nanocarrier (RGD peptide functionalized nanoparticles, RGD‐NPs) is reported for treating MDR hepatocellular carcinoma, which consists of three components: pH‐triggered calcium phosphate shell, long circulation phosphatidylserine‐polyethylene glycol (PS‐PEG) core, and an active targeting ligand RGD peptide. Drug‐resistance inhibitor (verapamil, VER) and chemotherapeutic agent (mitoxantrone, MIT) are separately encapsulated into the outer shell layer and inner core layer to obtain VER and MIT loaded RGD‐NPs (VM‐RGD‐NPs). Due to the shell–core structure, the VER and MIT can release sequentially, thus synergistically weakening the efflux effect to MIT by MDR cells. Also, the calcium phosphate can trigger lysosomal escaping through the varied pH value. Together with the optimized internalization pathway in MDR tumor cells, the increased intracellular effective chemotherapeutic drug concentration can be realized, thus achieving the improved curative effect. In this system, the PEG extends the circulation time in vivo. Also, the peptide RGD distinctly increases the affinity to MDR tumors with respect to nontargeted nanoparticles. As a consequence, VM‐RGD‐NPs exhibit a significant synergistic effect toward the MDR hepatocellular carcinoma, providing a promising therapeutic approach for MDR tumor.
An Integrated Multifunctional Nanoplatform for Deep‐Tissue Dual‐Mode Imaging
Authors: Yang Fan , Skripka Artiom , Benayas Antonio , Dong Xianke , Hong Sung Hwa , Ren Fuqiang , Oh Jung Kwon , Liu Xinyu , Vetrone Fiorenzo , Ma Dongling 
Published: January 2018

AbstractThe combination of biocompatible superparamagnetic and photoluminescent nanoparticles (NPs) is intensively studied as highly promising multifunctional (magnetic confinement and targeting, imaging, etc.) tools in biomedical applications. However, most of these hybrid NPs exhibit low signal contrast and shallow tissue penetration for optical imaging due to tissue‐induced optical extinction and autofluorescence, since in many cases, their photoluminescent components emit in the visible spectral range. Yet, the search for multifunctional NPs suitable for high photoluminescence signal‐to‐noise ratio, deep‐tissue imaging is still ongoing. Herein, a biocompatible core/shell/shell sandwich structured Fe3O4@SiO2@NaYF4:Nd3+ nanoplatform possessing excellent superparamagnetic and near‐infrared (excitation) to near‐infrared (emission), i.e., NIR‐to‐NIR photoluminescence properties is developed. They can be rapidly magnetically confined, allowing the NIR photoluminescence signal to be detected through a tissue as thick as 13 mm, accompanied by high T2 relaxivity in magnetic resonance imaging. The fact that both the excitation and emission wavelengths of these NPs are in the optically transparent biological windows, along with excellent photostability, fast magnetic response, significant T2‐contrast enhancement, and negligible cytotoxicity, makes them extremely promising for use in high‐resolution, deep‐tissue dual‐mode (optical and magnetic resonance) in vivo imaging and magnetic‐driven applications.