Identifying key regulators of the intestinal stem cell niche
Biochem Soc Trans. 2021 Oct 19:BST20210223. doi: 10.1042/BST20210223. Online ahead of print.ABSTRACTThe intestinal tract is lined by a single layer of epithelium that is one of the fastest regenerating tissues in the body and which therefore requires a very active and exquisitely controlled stem cell population. Rapid renewal of the epithelium is necessary to provide a continuous physical barrier from the intestinal luminal microenvironment that contains abundant microorganisms, whilst also ensuring an efficient surface for the absorption of dietary components. Specialised epithelial cell populations are important for the ...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Carrie A Duckworth Source Type: research

Programmed DNA elimination: silencing genes and repetitive sequences in somatic cells
Biochem Soc Trans. 2021 Oct 19:BST20190951. doi: 10.1042/BST20190951. Online ahead of print.ABSTRACTIn a multicellular organism, the genomes of all cells are in general the same. Programmed DNA elimination is a notable exception to this genome constancy rule. DNA elimination removes genes and repetitive elements in the germline genome to form a reduced somatic genome in various organisms. The process of DNA elimination within an organism is highly accurate and reproducible; it typically occurs during early embryogenesis, coincident with germline-soma differentiation. DNA elimination provides a mechanism to silence selected...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Maxim V Zagoskin Jianbin Wang Source Type: research

Itaconate as an inflammatory mediator and therapeutic target in cardiovascular medicine
Biochem Soc Trans. 2021 Oct 19:BST20210269. doi: 10.1042/BST20210269. Online ahead of print.ABSTRACTInflammation is a critical component of cardiovascular disease (CVD), encompassing coronary artery disease (CAD), cerebrovascular events and heart failure and is the leading cause of mortality worldwide. In recent years, metabolism has been placed centrally in the governance of the immune response. Termed immunometabolism, immune cells adapt cellular metabolic pathways to meet demands of activation and thus function. This rewiring influences not only the bioenergetics of the cell but altered metabolites act as signalling mol...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Marina Diotallevi Faseeha Ayaz Thomas Nicol Mark J Crabtree Source Type: research

The dynamics of mitochondrial autophagy at the initiation stage
Biochem Soc Trans. 2021 Oct 19:BST20210272. doi: 10.1042/BST20210272. Online ahead of print.ABSTRACTThe pathway of mitochondrial-specific autophagy (mitophagy, defined here as the specific elimination of mitochondria following distinct mitochondrial injuries or developmental/metabolic alterations) is important in health and disease. This review will be focussed on the earliest steps of the pathway concerning the mechanisms and requirements for initiating autophagosome formation on a mitochondrial target. More specifically, and in view of the fact that we understand the basic mechanism of non-selective autophagy and are beg...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Nicholas T Ktistakis Source Type: research

Identifying key regulators of the intestinal stem cell niche
Biochem Soc Trans. 2021 Oct 19:BST20210223. doi: 10.1042/BST20210223. Online ahead of print.ABSTRACTThe intestinal tract is lined by a single layer of epithelium that is one of the fastest regenerating tissues in the body and which therefore requires a very active and exquisitely controlled stem cell population. Rapid renewal of the epithelium is necessary to provide a continuous physical barrier from the intestinal luminal microenvironment that contains abundant microorganisms, whilst also ensuring an efficient surface for the absorption of dietary components. Specialised epithelial cell populations are important for the ...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Carrie A Duckworth Source Type: research

Programmed DNA elimination: silencing genes and repetitive sequences in somatic cells
Biochem Soc Trans. 2021 Oct 19:BST20190951. doi: 10.1042/BST20190951. Online ahead of print.ABSTRACTIn a multicellular organism, the genomes of all cells are in general the same. Programmed DNA elimination is a notable exception to this genome constancy rule. DNA elimination removes genes and repetitive elements in the germline genome to form a reduced somatic genome in various organisms. The process of DNA elimination within an organism is highly accurate and reproducible; it typically occurs during early embryogenesis, coincident with germline-soma differentiation. DNA elimination provides a mechanism to silence selected...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Maxim V Zagoskin Jianbin Wang Source Type: research

Itaconate as an inflammatory mediator and therapeutic target in cardiovascular medicine
Biochem Soc Trans. 2021 Oct 19:BST20210269. doi: 10.1042/BST20210269. Online ahead of print.ABSTRACTInflammation is a critical component of cardiovascular disease (CVD), encompassing coronary artery disease (CAD), cerebrovascular events and heart failure and is the leading cause of mortality worldwide. In recent years, metabolism has been placed centrally in the governance of the immune response. Termed immunometabolism, immune cells adapt cellular metabolic pathways to meet demands of activation and thus function. This rewiring influences not only the bioenergetics of the cell but altered metabolites act as signalling mol...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Marina Diotallevi Faseeha Ayaz Thomas Nicol Mark J Crabtree Source Type: research

The dynamics of mitochondrial autophagy at the initiation stage
Biochem Soc Trans. 2021 Oct 19:BST20210272. doi: 10.1042/BST20210272. Online ahead of print.ABSTRACTThe pathway of mitochondrial-specific autophagy (mitophagy, defined here as the specific elimination of mitochondria following distinct mitochondrial injuries or developmental/metabolic alterations) is important in health and disease. This review will be focussed on the earliest steps of the pathway concerning the mechanisms and requirements for initiating autophagosome formation on a mitochondrial target. More specifically, and in view of the fact that we understand the basic mechanism of non-selective autophagy and are beg...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Nicholas T Ktistakis Source Type: research

Identifying key regulators of the intestinal stem cell niche
Biochem Soc Trans. 2021 Oct 19:BST20210223. doi: 10.1042/BST20210223. Online ahead of print.ABSTRACTThe intestinal tract is lined by a single layer of epithelium that is one of the fastest regenerating tissues in the body and which therefore requires a very active and exquisitely controlled stem cell population. Rapid renewal of the epithelium is necessary to provide a continuous physical barrier from the intestinal luminal microenvironment that contains abundant microorganisms, whilst also ensuring an efficient surface for the absorption of dietary components. Specialised epithelial cell populations are important for the ...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Carrie A Duckworth Source Type: research

Programmed DNA elimination: silencing genes and repetitive sequences in somatic cells
Biochem Soc Trans. 2021 Oct 19:BST20190951. doi: 10.1042/BST20190951. Online ahead of print.ABSTRACTIn a multicellular organism, the genomes of all cells are in general the same. Programmed DNA elimination is a notable exception to this genome constancy rule. DNA elimination removes genes and repetitive elements in the germline genome to form a reduced somatic genome in various organisms. The process of DNA elimination within an organism is highly accurate and reproducible; it typically occurs during early embryogenesis, coincident with germline-soma differentiation. DNA elimination provides a mechanism to silence selected...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Maxim V Zagoskin Jianbin Wang Source Type: research

Itaconate as an inflammatory mediator and therapeutic target in cardiovascular medicine
Biochem Soc Trans. 2021 Oct 19:BST20210269. doi: 10.1042/BST20210269. Online ahead of print.ABSTRACTInflammation is a critical component of cardiovascular disease (CVD), encompassing coronary artery disease (CAD), cerebrovascular events and heart failure and is the leading cause of mortality worldwide. In recent years, metabolism has been placed centrally in the governance of the immune response. Termed immunometabolism, immune cells adapt cellular metabolic pathways to meet demands of activation and thus function. This rewiring influences not only the bioenergetics of the cell but altered metabolites act as signalling mol...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Marina Diotallevi Faseeha Ayaz Thomas Nicol Mark J Crabtree Source Type: research

The dynamics of mitochondrial autophagy at the initiation stage
Biochem Soc Trans. 2021 Oct 19:BST20210272. doi: 10.1042/BST20210272. Online ahead of print.ABSTRACTThe pathway of mitochondrial-specific autophagy (mitophagy, defined here as the specific elimination of mitochondria following distinct mitochondrial injuries or developmental/metabolic alterations) is important in health and disease. This review will be focussed on the earliest steps of the pathway concerning the mechanisms and requirements for initiating autophagosome formation on a mitochondrial target. More specifically, and in view of the fact that we understand the basic mechanism of non-selective autophagy and are beg...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Nicholas T Ktistakis Source Type: research

Identifying key regulators of the intestinal stem cell niche
Biochem Soc Trans. 2021 Oct 19:BST20210223. doi: 10.1042/BST20210223. Online ahead of print.ABSTRACTThe intestinal tract is lined by a single layer of epithelium that is one of the fastest regenerating tissues in the body and which therefore requires a very active and exquisitely controlled stem cell population. Rapid renewal of the epithelium is necessary to provide a continuous physical barrier from the intestinal luminal microenvironment that contains abundant microorganisms, whilst also ensuring an efficient surface for the absorption of dietary components. Specialised epithelial cell populations are important for the ...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Carrie A Duckworth Source Type: research

Programmed DNA elimination: silencing genes and repetitive sequences in somatic cells
Biochem Soc Trans. 2021 Oct 19:BST20190951. doi: 10.1042/BST20190951. Online ahead of print.ABSTRACTIn a multicellular organism, the genomes of all cells are in general the same. Programmed DNA elimination is a notable exception to this genome constancy rule. DNA elimination removes genes and repetitive elements in the germline genome to form a reduced somatic genome in various organisms. The process of DNA elimination within an organism is highly accurate and reproducible; it typically occurs during early embryogenesis, coincident with germline-soma differentiation. DNA elimination provides a mechanism to silence selected...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Maxim V Zagoskin Jianbin Wang Source Type: research

Itaconate as an inflammatory mediator and therapeutic target in cardiovascular medicine
Biochem Soc Trans. 2021 Oct 19:BST20210269. doi: 10.1042/BST20210269. Online ahead of print.ABSTRACTInflammation is a critical component of cardiovascular disease (CVD), encompassing coronary artery disease (CAD), cerebrovascular events and heart failure and is the leading cause of mortality worldwide. In recent years, metabolism has been placed centrally in the governance of the immune response. Termed immunometabolism, immune cells adapt cellular metabolic pathways to meet demands of activation and thus function. This rewiring influences not only the bioenergetics of the cell but altered metabolites act as signalling mol...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Marina Diotallevi Faseeha Ayaz Thomas Nicol Mark J Crabtree Source Type: research

The dynamics of mitochondrial autophagy at the initiation stage
Biochem Soc Trans. 2021 Oct 19:BST20210272. doi: 10.1042/BST20210272. Online ahead of print.ABSTRACTThe pathway of mitochondrial-specific autophagy (mitophagy, defined here as the specific elimination of mitochondria following distinct mitochondrial injuries or developmental/metabolic alterations) is important in health and disease. This review will be focussed on the earliest steps of the pathway concerning the mechanisms and requirements for initiating autophagosome formation on a mitochondrial target. More specifically, and in view of the fact that we understand the basic mechanism of non-selective autophagy and are beg...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Nicholas T Ktistakis Source Type: research

Identifying key regulators of the intestinal stem cell niche
Biochem Soc Trans. 2021 Oct 19:BST20210223. doi: 10.1042/BST20210223. Online ahead of print.ABSTRACTThe intestinal tract is lined by a single layer of epithelium that is one of the fastest regenerating tissues in the body and which therefore requires a very active and exquisitely controlled stem cell population. Rapid renewal of the epithelium is necessary to provide a continuous physical barrier from the intestinal luminal microenvironment that contains abundant microorganisms, whilst also ensuring an efficient surface for the absorption of dietary components. Specialised epithelial cell populations are important for the ...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Carrie A Duckworth Source Type: research

Programmed DNA elimination: silencing genes and repetitive sequences in somatic cells
Biochem Soc Trans. 2021 Oct 19:BST20190951. doi: 10.1042/BST20190951. Online ahead of print.ABSTRACTIn a multicellular organism, the genomes of all cells are in general the same. Programmed DNA elimination is a notable exception to this genome constancy rule. DNA elimination removes genes and repetitive elements in the germline genome to form a reduced somatic genome in various organisms. The process of DNA elimination within an organism is highly accurate and reproducible; it typically occurs during early embryogenesis, coincident with germline-soma differentiation. DNA elimination provides a mechanism to silence selected...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Maxim V Zagoskin Jianbin Wang Source Type: research

Itaconate as an inflammatory mediator and therapeutic target in cardiovascular medicine
Biochem Soc Trans. 2021 Oct 19:BST20210269. doi: 10.1042/BST20210269. Online ahead of print.ABSTRACTInflammation is a critical component of cardiovascular disease (CVD), encompassing coronary artery disease (CAD), cerebrovascular events and heart failure and is the leading cause of mortality worldwide. In recent years, metabolism has been placed centrally in the governance of the immune response. Termed immunometabolism, immune cells adapt cellular metabolic pathways to meet demands of activation and thus function. This rewiring influences not only the bioenergetics of the cell but altered metabolites act as signalling mol...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Marina Diotallevi Faseeha Ayaz Thomas Nicol Mark J Crabtree Source Type: research

The dynamics of mitochondrial autophagy at the initiation stage
Biochem Soc Trans. 2021 Oct 19:BST20210272. doi: 10.1042/BST20210272. Online ahead of print.ABSTRACTThe pathway of mitochondrial-specific autophagy (mitophagy, defined here as the specific elimination of mitochondria following distinct mitochondrial injuries or developmental/metabolic alterations) is important in health and disease. This review will be focussed on the earliest steps of the pathway concerning the mechanisms and requirements for initiating autophagosome formation on a mitochondrial target. More specifically, and in view of the fact that we understand the basic mechanism of non-selective autophagy and are beg...
Source: Biochemical Society Transactions - October 19, 2021 Category: Biochemistry Authors: Nicholas T Ktistakis Source Type: research

Modeling of human T cell development in vitro as a read-out for hematopoietic stem cell multipotency
Biochem Soc Trans. 2021 Oct 13:BST20210144. doi: 10.1042/BST20210144. Online ahead of print.ABSTRACTHematopoietic stem cells (HSCs) reside in distinct sites throughout fetal and adult life and give rise to all cells of the hematopoietic system. Because of their multipotency, HSCs are capable of curing a wide variety of blood disorders through hematopoietic stem cell transplantation (HSCT). However, due to HSC heterogeneity, site-specific ontogeny and current limitations in generating and expanding HSCs in vitro, their broad use in clinical practice remains challenging. To assess HSC multipotency, evaluation of their capaci...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Steven Strubbe Tom Taghon Source Type: research

To export, or not to export: how nuclear export factor variants resolve Piwi's dilemma
Biochem Soc Trans. 2021 Oct 13:BST20201171. doi: 10.1042/BST20201171. Online ahead of print.ABSTRACTPiwi-interacting RNAs (piRNAs) defend animal gonads by guiding PIWI-clade Argonaute proteins to silence transposons. The nuclear Piwi/piRNA complexes confer transcriptional repression of transposons, which is accompanied with heterochromatin formation at target loci. On the other hand, piRNA clusters, genomic loci that transcribe piRNA precursors composed of transposon fragments, are often recognized by piRNAs to define their heterochromatic identity. Therefore, Piwi/piRNA complexes must resolve this conundrum of silencing t...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Sheng Wang Xiaohua Lu Ding Qiu Yang Yu Source Type: research

Biophysical characterisation of SMALPs
Biochem Soc Trans. 2021 Oct 13:BST20201088. doi: 10.1042/BST20201088. Online ahead of print.ABSTRACTMembrane proteins such as receptors, ion channels and transport proteins are important drug targets. The structure-based study of membrane proteins is challenging, especially when the target protein contains both soluble and insoluble domains. Most membrane proteins are insoluble in aqueous solvent and embedded in the plasma membrane lipid bilayer, which significantly complicates biophysical studies. Poly(styrene-co-maleic acid) (SMA) and other polymer derivatives are increasingly common solubilisation agents, used to isolat...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Stephanie A Nestorow Tim R Dafforn Verna Frasca Source Type: research

Ca2+-dependent modulation of voltage-gated myocyte sodium channels
Biochem Soc Trans. 2021 Oct 13:BST20200604. doi: 10.1042/BST20200604. Online ahead of print.ABSTRACTVoltage-dependent Na+ channel activation underlies action potential generation fundamental to cellular excitability. In skeletal and cardiac muscle this triggers contraction via ryanodine-receptor (RyR)-mediated sarcoplasmic reticular (SR) Ca2+ release. We here review potential feedback actions of intracellular [Ca2+] ([Ca2+]i) on Na+ channel activity, surveying their structural, genetic and cellular and functional implications, translating these to their possible clinical importance. In addition to phosphorylation sites, bo...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Samantha C Salvage Zaki F Habib Hugh R Matthews Antony P Jackson Christopher L-H Huang Source Type: research

Modeling of human T cell development in vitro as a read-out for hematopoietic stem cell multipotency
Biochem Soc Trans. 2021 Oct 13:BST20210144. doi: 10.1042/BST20210144. Online ahead of print.ABSTRACTHematopoietic stem cells (HSCs) reside in distinct sites throughout fetal and adult life and give rise to all cells of the hematopoietic system. Because of their multipotency, HSCs are capable of curing a wide variety of blood disorders through hematopoietic stem cell transplantation (HSCT). However, due to HSC heterogeneity, site-specific ontogeny and current limitations in generating and expanding HSCs in vitro, their broad use in clinical practice remains challenging. To assess HSC multipotency, evaluation of their capaci...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Steven Strubbe Tom Taghon Source Type: research

To export, or not to export: how nuclear export factor variants resolve Piwi's dilemma
Biochem Soc Trans. 2021 Oct 13:BST20201171. doi: 10.1042/BST20201171. Online ahead of print.ABSTRACTPiwi-interacting RNAs (piRNAs) defend animal gonads by guiding PIWI-clade Argonaute proteins to silence transposons. The nuclear Piwi/piRNA complexes confer transcriptional repression of transposons, which is accompanied with heterochromatin formation at target loci. On the other hand, piRNA clusters, genomic loci that transcribe piRNA precursors composed of transposon fragments, are often recognized by piRNAs to define their heterochromatic identity. Therefore, Piwi/piRNA complexes must resolve this conundrum of silencing t...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Sheng Wang Xiaohua Lu Ding Qiu Yang Yu Source Type: research

Biophysical characterisation of SMALPs
Biochem Soc Trans. 2021 Oct 13:BST20201088. doi: 10.1042/BST20201088. Online ahead of print.ABSTRACTMembrane proteins such as receptors, ion channels and transport proteins are important drug targets. The structure-based study of membrane proteins is challenging, especially when the target protein contains both soluble and insoluble domains. Most membrane proteins are insoluble in aqueous solvent and embedded in the plasma membrane lipid bilayer, which significantly complicates biophysical studies. Poly(styrene-co-maleic acid) (SMA) and other polymer derivatives are increasingly common solubilisation agents, used to isolat...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Stephanie A Nestorow Tim R Dafforn Verna Frasca Source Type: research

Ca2+-dependent modulation of voltage-gated myocyte sodium channels
Biochem Soc Trans. 2021 Oct 13:BST20200604. doi: 10.1042/BST20200604. Online ahead of print.ABSTRACTVoltage-dependent Na+ channel activation underlies action potential generation fundamental to cellular excitability. In skeletal and cardiac muscle this triggers contraction via ryanodine-receptor (RyR)-mediated sarcoplasmic reticular (SR) Ca2+ release. We here review potential feedback actions of intracellular [Ca2+] ([Ca2+]i) on Na+ channel activity, surveying their structural, genetic and cellular and functional implications, translating these to their possible clinical importance. In addition to phosphorylation sites, bo...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Samantha C Salvage Zaki F Habib Hugh R Matthews Antony P Jackson Christopher L-H Huang Source Type: research

Modeling of human T cell development in vitro as a read-out for hematopoietic stem cell multipotency
Biochem Soc Trans. 2021 Oct 13:BST20210144. doi: 10.1042/BST20210144. Online ahead of print.ABSTRACTHematopoietic stem cells (HSCs) reside in distinct sites throughout fetal and adult life and give rise to all cells of the hematopoietic system. Because of their multipotency, HSCs are capable of curing a wide variety of blood disorders through hematopoietic stem cell transplantation (HSCT). However, due to HSC heterogeneity, site-specific ontogeny and current limitations in generating and expanding HSCs in vitro, their broad use in clinical practice remains challenging. To assess HSC multipotency, evaluation of their capaci...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Steven Strubbe Tom Taghon Source Type: research

To export, or not to export: how nuclear export factor variants resolve Piwi's dilemma
Biochem Soc Trans. 2021 Oct 13:BST20201171. doi: 10.1042/BST20201171. Online ahead of print.ABSTRACTPiwi-interacting RNAs (piRNAs) defend animal gonads by guiding PIWI-clade Argonaute proteins to silence transposons. The nuclear Piwi/piRNA complexes confer transcriptional repression of transposons, which is accompanied with heterochromatin formation at target loci. On the other hand, piRNA clusters, genomic loci that transcribe piRNA precursors composed of transposon fragments, are often recognized by piRNAs to define their heterochromatic identity. Therefore, Piwi/piRNA complexes must resolve this conundrum of silencing t...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Sheng Wang Xiaohua Lu Ding Qiu Yang Yu Source Type: research

Biophysical characterisation of SMALPs
Biochem Soc Trans. 2021 Oct 13:BST20201088. doi: 10.1042/BST20201088. Online ahead of print.ABSTRACTMembrane proteins such as receptors, ion channels and transport proteins are important drug targets. The structure-based study of membrane proteins is challenging, especially when the target protein contains both soluble and insoluble domains. Most membrane proteins are insoluble in aqueous solvent and embedded in the plasma membrane lipid bilayer, which significantly complicates biophysical studies. Poly(styrene-co-maleic acid) (SMA) and other polymer derivatives are increasingly common solubilisation agents, used to isolat...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Stephanie A Nestorow Tim R Dafforn Verna Frasca Source Type: research

Ca2+-dependent modulation of voltage-gated myocyte sodium channels
Biochem Soc Trans. 2021 Oct 13:BST20200604. doi: 10.1042/BST20200604. Online ahead of print.ABSTRACTVoltage-dependent Na+ channel activation underlies action potential generation fundamental to cellular excitability. In skeletal and cardiac muscle this triggers contraction via ryanodine-receptor (RyR)-mediated sarcoplasmic reticular (SR) Ca2+ release. We here review potential feedback actions of intracellular [Ca2+] ([Ca2+]i) on Na+ channel activity, surveying their structural, genetic and cellular and functional implications, translating these to their possible clinical importance. In addition to phosphorylation sites, bo...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Samantha C Salvage Zaki F Habib Hugh R Matthews Antony P Jackson Christopher L-H Huang Source Type: research

Modeling of human T cell development in vitro as a read-out for hematopoietic stem cell multipotency
Biochem Soc Trans. 2021 Oct 13:BST20210144. doi: 10.1042/BST20210144. Online ahead of print.ABSTRACTHematopoietic stem cells (HSCs) reside in distinct sites throughout fetal and adult life and give rise to all cells of the hematopoietic system. Because of their multipotency, HSCs are capable of curing a wide variety of blood disorders through hematopoietic stem cell transplantation (HSCT). However, due to HSC heterogeneity, site-specific ontogeny and current limitations in generating and expanding HSCs in vitro, their broad use in clinical practice remains challenging. To assess HSC multipotency, evaluation of their capaci...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Steven Strubbe Tom Taghon Source Type: research

To export, or not to export: how nuclear export factor variants resolve Piwi's dilemma
Biochem Soc Trans. 2021 Oct 13:BST20201171. doi: 10.1042/BST20201171. Online ahead of print.ABSTRACTPiwi-interacting RNAs (piRNAs) defend animal gonads by guiding PIWI-clade Argonaute proteins to silence transposons. The nuclear Piwi/piRNA complexes confer transcriptional repression of transposons, which is accompanied with heterochromatin formation at target loci. On the other hand, piRNA clusters, genomic loci that transcribe piRNA precursors composed of transposon fragments, are often recognized by piRNAs to define their heterochromatic identity. Therefore, Piwi/piRNA complexes must resolve this conundrum of silencing t...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Sheng Wang Xiaohua Lu Ding Qiu Yang Yu Source Type: research

Biophysical characterisation of SMALPs
Biochem Soc Trans. 2021 Oct 13:BST20201088. doi: 10.1042/BST20201088. Online ahead of print.ABSTRACTMembrane proteins such as receptors, ion channels and transport proteins are important drug targets. The structure-based study of membrane proteins is challenging, especially when the target protein contains both soluble and insoluble domains. Most membrane proteins are insoluble in aqueous solvent and embedded in the plasma membrane lipid bilayer, which significantly complicates biophysical studies. Poly(styrene-co-maleic acid) (SMA) and other polymer derivatives are increasingly common solubilisation agents, used to isolat...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Stephanie A Nestorow Tim R Dafforn Verna Frasca Source Type: research

Ca2+-dependent modulation of voltage-gated myocyte sodium channels
Biochem Soc Trans. 2021 Oct 13:BST20200604. doi: 10.1042/BST20200604. Online ahead of print.ABSTRACTVoltage-dependent Na+ channel activation underlies action potential generation fundamental to cellular excitability. In skeletal and cardiac muscle this triggers contraction via ryanodine-receptor (RyR)-mediated sarcoplasmic reticular (SR) Ca2+ release. We here review potential feedback actions of intracellular [Ca2+] ([Ca2+]i) on Na+ channel activity, surveying their structural, genetic and cellular and functional implications, translating these to their possible clinical importance. In addition to phosphorylation sites, bo...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Samantha C Salvage Zaki F Habib Hugh R Matthews Antony P Jackson Christopher L-H Huang Source Type: research

Modeling of human T cell development in vitro as a read-out for hematopoietic stem cell multipotency
Biochem Soc Trans. 2021 Oct 13:BST20210144. doi: 10.1042/BST20210144. Online ahead of print.ABSTRACTHematopoietic stem cells (HSCs) reside in distinct sites throughout fetal and adult life and give rise to all cells of the hematopoietic system. Because of their multipotency, HSCs are capable of curing a wide variety of blood disorders through hematopoietic stem cell transplantation (HSCT). However, due to HSC heterogeneity, site-specific ontogeny and current limitations in generating and expanding HSCs in vitro, their broad use in clinical practice remains challenging. To assess HSC multipotency, evaluation of their capaci...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Steven Strubbe Tom Taghon Source Type: research

To export, or not to export: how nuclear export factor variants resolve Piwi's dilemma
Biochem Soc Trans. 2021 Oct 13:BST20201171. doi: 10.1042/BST20201171. Online ahead of print.ABSTRACTPiwi-interacting RNAs (piRNAs) defend animal gonads by guiding PIWI-clade Argonaute proteins to silence transposons. The nuclear Piwi/piRNA complexes confer transcriptional repression of transposons, which is accompanied with heterochromatin formation at target loci. On the other hand, piRNA clusters, genomic loci that transcribe piRNA precursors composed of transposon fragments, are often recognized by piRNAs to define their heterochromatic identity. Therefore, Piwi/piRNA complexes must resolve this conundrum of silencing t...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Sheng Wang Xiaohua Lu Ding Qiu Yang Yu Source Type: research

Biophysical characterisation of SMALPs
Biochem Soc Trans. 2021 Oct 13:BST20201088. doi: 10.1042/BST20201088. Online ahead of print.ABSTRACTMembrane proteins such as receptors, ion channels and transport proteins are important drug targets. The structure-based study of membrane proteins is challenging, especially when the target protein contains both soluble and insoluble domains. Most membrane proteins are insoluble in aqueous solvent and embedded in the plasma membrane lipid bilayer, which significantly complicates biophysical studies. Poly(styrene-co-maleic acid) (SMA) and other polymer derivatives are increasingly common solubilisation agents, used to isolat...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Stephanie A Nestorow Tim R Dafforn Verna Frasca Source Type: research

Ca2+-dependent modulation of voltage-gated myocyte sodium channels
Biochem Soc Trans. 2021 Oct 13:BST20200604. doi: 10.1042/BST20200604. Online ahead of print.ABSTRACTVoltage-dependent Na+ channel activation underlies action potential generation fundamental to cellular excitability. In skeletal and cardiac muscle this triggers contraction via ryanodine-receptor (RyR)-mediated sarcoplasmic reticular (SR) Ca2+ release. We here review potential feedback actions of intracellular [Ca2+] ([Ca2+]i) on Na+ channel activity, surveying their structural, genetic and cellular and functional implications, translating these to their possible clinical importance. In addition to phosphorylation sites, bo...
Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Samantha C Salvage Zaki F Habib Hugh R Matthews Antony P Jackson Christopher L-H Huang Source Type: research

Targeting small GTPases and their downstream pathways with intracellular macromolecule binders to define alternative therapeutic strategies in cancer
Biochem Soc Trans. 2021 Oct 8:BST20201059. doi: 10.1042/BST20201059. Online ahead of print.ABSTRACTThe RAS superfamily of small GTPases regulates major physiological cellular processes. Mutation or deregulation of these small GTPases, their regulators and/or their effectors are associated with many diseases including cancer. Hence, targeting these classes of proteins is an important therapeutic strategy in cancer. This has been recently achieved with the approval of the first KRASG12C covalent inhibitors for the clinic. However, many other mutants and small GTPases are still considered as 'undruggable' with small molecule ...
Source: Biochemical Society Transactions - October 8, 2021 Category: Biochemistry Authors: Marie Sorbara Nicolas Bery Source Type: research

How activated NLRs induce anti-microbial defenses in plants
Biochem Soc Trans. 2021 Oct 8:BST20210242. doi: 10.1042/BST20210242. Online ahead of print.ABSTRACTPlants utilize cell-surface localized and intracellular leucine-rich repeat (LRR) immune receptors to detect pathogens and to activate defense responses, including transcriptional reprogramming and the initiation of a form of programmed cell death of infected cells. Cell death initiation is mainly associated with the activation of nucleotide-binding LRR receptors (NLRs). NLRs recognize the presence or cellular activity of pathogen-derived virulence proteins, so-called effectors. Effector-dependent NLR activation leads to the ...
Source: Biochemical Society Transactions - October 8, 2021 Category: Biochemistry Authors: Farid El Kasmi Source Type: research

Thermodynamic and structural basis of temperature-dependent gating in TRP channels
Biochem Soc Trans. 2021 Oct 8:BST20210301. doi: 10.1042/BST20210301. Online ahead of print.ABSTRACTLiving organisms require detecting the environmental thermal clues for survival, allowing them to avoid noxious stimuli or find prey moving in the dark. In mammals, the Transient Receptor Potential ion channels superfamily is constituted by 27 polymodal receptors whose activity is controlled by small ligands, peptide toxins, protons and voltage. The thermoTRP channels subgroup exhibits unparalleled temperature dependence -behaving as heat and cold sensors. Functional studies have dissected their biophysical features in detail...
Source: Biochemical Society Transactions - October 8, 2021 Category: Biochemistry Authors: Ignacio Diaz-Franulic Christian Verdugo Felipe Gonzalez Fernando Gonzalez-Nilo Ramon Latorre Source Type: research

Structural biology of human telomerase: progress and prospects
Biochem Soc Trans. 2021 Oct 8:BST20200042. doi: 10.1042/BST20200042. Online ahead of print.ABSTRACTTelomerase ribonucleoprotein was discovered over three decades ago as a specialized reverse transcriptase that adds telomeric repeats to the ends of linear eukaryotic chromosomes. Telomerase plays key roles in maintaining genome stability; and its dysfunction and misregulation have been linked to different types of cancers and a spectrum of human genetic disorders. Over the years, a wealth of genetic and biochemical studies of human telomerase have illuminated its numerous fascinating features. Yet, structural studies of huma...
Source: Biochemical Society Transactions - October 8, 2021 Category: Biochemistry Authors: Thi Hoang Duong Nguyen Source Type: research

Controlled metabolic cascades for protein synthesis in an artificial cell
Biochem Soc Trans. 2021 Oct 8:BST20210175. doi: 10.1042/BST20210175. Online ahead of print.ABSTRACTIn recent years, researchers have been pursuing a method to design and to construct life forms from scratch - in other words, to create artificial cells. In many studies, artificial cellular membranes have been successfully fabricated, allowing the research field to grow by leaps and bounds. Moreover, in addition to lipid bilayer membranes, proteins are essential factors required to construct any cellular metabolic reaction; for that reason, different cell-free expression systems under various conditions to achieve the goal o...
Source: Biochemical Society Transactions - October 8, 2021 Category: Biochemistry Authors: Huong Thanh Nguyen Sungwoo Lee Kwanwoo Shin Source Type: research

Improving photosynthesis through the enhancement of Rubisco carboxylation capacity
Biochem Soc Trans. 2021 Oct 8:BST20201056. doi: 10.1042/BST20201056. Online ahead of print.ABSTRACTRising human population, along with the reduction in arable land and the impacts of global change, sets out the need for continuously improving agricultural resource use efficiency and crop yield (CY). Bioengineering approaches for photosynthesis optimization have largely demonstrated the potential for enhancing CY. This review is focused on the improvement of Rubisco functioning, which catalyzes the rate-limiting step of CO2 fixation required for plant growth, but also catalyzes the ribulose-bisphosphate oxygenation initiati...
Source: Biochemical Society Transactions - October 8, 2021 Category: Biochemistry Authors: Concepci ón Iñiguez Pere Aguil ó-Nicolau Jeroni Galm és Source Type: research

An integrated view of innate immune mechanisms in C. elegans
Biochem Soc Trans. 2021 Oct 8:BST20210399. doi: 10.1042/BST20210399. Online ahead of print.ABSTRACTThe simple notion 'infection causes an immune response' is being progressively refined as it becomes clear that immune mechanisms cannot be understood in isolation, but need to be considered in a more global context with other cellular and physiological processes. In part, this reflects the deployment by pathogens of virulence factors that target diverse cellular processes, such as translation or mitochondrial respiration, often with great molecular specificity. It also reflects molecular cross-talk between a broad range of h...
Source: Biochemical Society Transactions - October 8, 2021 Category: Biochemistry Authors: Benjamin W Harding Jonathan J Ewbank Source Type: research

Targeting small GTPases and their downstream pathways with intracellular macromolecule binders to define alternative therapeutic strategies in cancer
Biochem Soc Trans. 2021 Oct 8:BST20201059. doi: 10.1042/BST20201059. Online ahead of print.ABSTRACTThe RAS superfamily of small GTPases regulates major physiological cellular processes. Mutation or deregulation of these small GTPases, their regulators and/or their effectors are associated with many diseases including cancer. Hence, targeting these classes of proteins is an important therapeutic strategy in cancer. This has been recently achieved with the approval of the first KRASG12C covalent inhibitors for the clinic. However, many other mutants and small GTPases are still considered as 'undruggable' with small molecule ...
Source: Biochemical Society Transactions - October 8, 2021 Category: Biochemistry Authors: Marie Sorbara Nicolas Bery Source Type: research

How activated NLRs induce anti-microbial defenses in plants
Biochem Soc Trans. 2021 Oct 8:BST20210242. doi: 10.1042/BST20210242. Online ahead of print.ABSTRACTPlants utilize cell-surface localized and intracellular leucine-rich repeat (LRR) immune receptors to detect pathogens and to activate defense responses, including transcriptional reprogramming and the initiation of a form of programmed cell death of infected cells. Cell death initiation is mainly associated with the activation of nucleotide-binding LRR receptors (NLRs). NLRs recognize the presence or cellular activity of pathogen-derived virulence proteins, so-called effectors. Effector-dependent NLR activation leads to the ...
Source: Biochemical Society Transactions - October 8, 2021 Category: Biochemistry Authors: Farid El Kasmi Source Type: research

Thermodynamic and structural basis of temperature-dependent gating in TRP channels
Biochem Soc Trans. 2021 Oct 8:BST20210301. doi: 10.1042/BST20210301. Online ahead of print.ABSTRACTLiving organisms require detecting the environmental thermal clues for survival, allowing them to avoid noxious stimuli or find prey moving in the dark. In mammals, the Transient Receptor Potential ion channels superfamily is constituted by 27 polymodal receptors whose activity is controlled by small ligands, peptide toxins, protons and voltage. The thermoTRP channels subgroup exhibits unparalleled temperature dependence -behaving as heat and cold sensors. Functional studies have dissected their biophysical features in detail...
Source: Biochemical Society Transactions - October 8, 2021 Category: Biochemistry Authors: Ignacio Diaz-Franulic Christian Verdugo Felipe Gonzalez Fernando Gonzalez-Nilo Ramon Latorre Source Type: research