C4-dicarboxylates as growth substrates and signaling molecules for commensal and pathogenic enteric bacteria in mammalian intestine

The C4-dicarboxylates (C4-DC) L-aspartate and L-malate have been identified as playing an important role in the colonization of mammalian intestine by enteric bacteria, such as Escherichia coli and Salmonella Typhimurium, and succinate as a signaling molecule for host–enteric bacteria interaction. Thus, endogenous and exogenous fumarate respiration and related functions are required for efficient initial growth of the bacteria. L-aspartate represents a major substrate for fumarate respiration in the intestine and a high-quality substrate for nitrogen assimilation. During nitrogen assimilation, DcuA catalyzes an L-aspartate/fumarate antiport and serves as a nitrogen shuttle for the net uptake of ammonium only, whereas DcuB acts as a redox shuttle that catalyzes the L-malate/succinate antiport during fumarate respiration. The C4-DC two-component system DcuS-DcuR is active in the intestine and responds to intestinal C4-DC levels. Moreover, in macrophages and in mice, succinate is a signal that promotes virulence and survival of S . Tm and pathogenic E. coli . On the other hand, intestinal succinate is an important signaling molecule for the host and activates response and protective programs. Therefore, C4-DCs play a major role in supporting colonization of enteric bacteria and as signaling molecules for the adaptation of host physiology.

Metformin’s Therapeutic Action in the Treatment of Diabetes Does Not Involve Inhibition of Mitochondrial Glycerol Phosphate Dehydrogenase

Mitochondrial glycerol phosphate dehydrogenase (mGPD) is the rate-limiting enzyme of the glycerol phosphate redox shuttle. It was recently claimed that metformin, a first line drug used for the treatment of type 2 diabetes, inhibits liver mGPD 30-50% suppressing gluconeogenesis through a redox mechanism. Various factors cast doubt on this idea. Total body100% knockout of mGPD in mice has adverse effects in several tissues where mGPD is high, but has little or no effect in liver where mGPD is the lowest of ten tissues. Metformin has beneficial effects in humans in tissues with high levels of mGPD such as pancreatic beta cells where mGPD is much higher than in liver. Insulin secretion in mGPD knockout mouse beta cells is normal because, like liver, beta cells possess the malate aspartate redox shuttle that’s redox action is redundant to the glycerol phosphate shuttle. For these and other reasons we used four different enzyme assays to reassess whether metformin inhibited mGPD. Metformin did not inhibit mGPD in homogenates or mitochondria from insulin cells or liver cells. If metformin actually inhibited mGPD, adverse effects in tissues where the level of mGPD is much higher than in liver could prevent metformin’s use as a diabetes medicine.

Poly(ethylene Glycol-Block-2-Ethyl-2-Oxazoline) as Cathode Binder in Lithium-Sulfur Batteries

Functional binders constitute a strategy to overcome several challenges that lithium–sulfur (Li–S) batteries are facing due to soluble reaction intermediates in the positive electrode. Poly(ethylene oxide) (PEO) and poly(vinylpyrrolidone) (PVP) are in this context a previously well-explored binder mixture. Their ether and amide groups possess affinity to the dissolved sulfur species, which enhances the sulfur utilization and mitigates the parasitic redox shuttle. However, the immiscibility of PEO and PVP is a concern for electrode stability. Copolymers comprising ether and amide groups are thus promising candidates to improve the stability the system. Here, a series of poly(ethylene glycol-block-2-ethyl-2-oxazoline) with various block lengths is synthesized and explored as binders in S/C composite electrodes in Li-S cells. While the electrochemical analyses show that although the sulfur utilization and capacity retention of the tested electrodes are similar, the integrity of the as-cast electrodes can play a key role for power capability.<br>

Poly(ethylene Glycol-Block-2-Ethyl-2-Oxazoline) as Cathode Binder in Lithium-Sulfur Batteries

Functional binders constitute a strategy to overcome several challenges that lithium–sulfur (Li–S) batteries are facing due to soluble reaction intermediates in the positive electrode. Poly(ethylene oxide) (PEO) and poly(vinylpyrrolidone) (PVP) are in this context a previously well-explored binder mixture. Their ether and amide groups possess affinity to the dissolved sulfur species, which enhances the sulfur utilization and mitigates the parasitic redox shuttle. However, the immiscibility of PEO and PVP is a concern for electrode stability. Copolymers comprising ether and amide groups are thus promising candidates to improve the stability the system. Here, a series of poly(ethylene glycol-block-2-ethyl-2-oxazoline) with various block lengths is synthesized and explored as binders in S/C composite electrodes in Li-S cells. While the electrochemical analyses show that although the sulfur utilization and capacity retention of the tested electrodes are similar, the integrity of the as-cast electrodes can play a key role for power capability.<br>

Metformin’s Therapeutic Action in the Treatment of Diabetes Does Not Involve Inhibition of Mitochondrial Glycerol Phosphate Dehydrogenase

Mitochondrial glycerol phosphate dehydrogenase (mGPD) is the rate-limiting enzyme of the glycerol phosphate redox shuttle. It was recently claimed that metformin, a first line drug used for the treatment of type 2 diabetes, inhibits liver mGPD 30-50% suppressing gluconeogenesis through a redox mechanism. Various factors cast doubt on this idea. Total body100% knockout of mGPD in mice has adverse effects in several tissues where mGPD is high, but has little or no effect in liver where mGPD is the lowest of ten tissues. Metformin has beneficial effects in humans in tissues with high levels of mGPD such as pancreatic beta cells where mGPD is much higher than in liver. Insulin secretion in mGPD knockout mouse beta cells is normal because, like liver, beta cells possess the malate aspartate redox shuttle that’s redox action is redundant to the glycerol phosphate shuttle. For these and other reasons we used four different enzyme assays to reassess whether metformin inhibited mGPD. Metformin did not inhibit mGPD in homogenates or mitochondria from insulin cells or liver cells. If metformin actually inhibited mGPD, adverse effects in tissues where the level of mGPD is much higher than in liver could prevent metformin’s use as a diabetes medicine.