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The glucokinase protein sequence is most closely related
2021-12-07

The glucokinase protein sequence is most closely related to the C-terminal domain of 100kD hexokinases, thus for glucokinase to evolve from a larger hexokinase ancestor it must have lost its N-terminal kinase domain. The genetic mechanism by which this occurred is currently unknown. Here we propose
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br Acknowledgements This work was supported by a
2021-12-07

Acknowledgements This work was supported by a fellowship to C.H. under the ‘100 Foreign Expert’ scheme of the Shanxi province government(R100456). Conflict of interest: Dr. Holscher is a named inventor on a patent submitted by Lancaster University on the use of dual GLP-1/GIP analogues in neurode
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In the a first in
2021-12-06

In the 2003, a first in vitro indication of modulation of FXR expression in CRC showed that FXR expression was absent in undifferentiated colon carcinoma cell line SW480, while it was progressively increasing along with the degree of cell differentiation in Caco2 and HT29 cells, and its transcriptio
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Accordingly and in animal models a high fat diet
2021-12-06

Accordingly and in animal models, a high-fat diet rich in CO (CO-HFD) impeded ventricular function and induced cardiac cell death and remodeling, at least, by down-regulating cell antioxidant defense systems and induction of oxidative stress [28], [29], [30], [31]. Interestingly, long chain fatty ac
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Senger et al performed a retrospective review
2021-12-06

Senger et al. performed a retrospective review of 17 patients with ICH on dabigatran or rivaroxaban who received 4F-PCC. Eight patients had a traumatic p2y inhibitor injury (TBI) and nine patients had a spontaneous ICH. Nine patients had a devastating outcome, including severe neurologic deficits,
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Our understanding of the genetic basis of myeloid malignanci
2021-12-06

Our understanding of the genetic basis of myeloid malignancies has been profoundly improved in recent years. Studies have revealed new recurrent somatic mutations in myeloid malignancies, including myeloproliferative neoplasms (MPNs), myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML).
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Thus from this preliminary study a working model
2021-12-06

Thus from this preliminary study, a working model of HIV-1 integrase was developed from which a selective inhibitor of the strand-transfer reaction displaying whole-cell activity and negligible cytotoxicity was produced. Compound 9 provides a promising scaffold for further elaboration, and current i
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In the CNS histamine is known to regulate
2021-12-06

In the CNS, trpv1 antagonist is known to regulate sleep and wakefulness, learning and memory, feeding, and energy. Here, we address its actions in relation to CNS disorders, and emphasize potential clinical applications of histamine receptor ligands (Table 1). In addition, as the effect of histamin
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Third across all three signaling
2021-12-06

Third, across all three signaling molecules examined, the baseline abnormalities seen in Hdc-KO mice resemble the effects seen after H3R activation in wild-type animals. Specifically, MAPK activity (indexed by MSK1 phosphorylation) is increased at baseline in dMSNs of Hdc-KO mice to a similar degree
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The presence of the H receptor in
2021-12-06

The presence of the H3 receptor in humans was confirmed approximately 25 years ago, and the receptor was successfully cloned in 1999 (Thurmond, 2010). The H3 receptor is unique, as it controls feedback of histamine release, particularly in the central nervous system, where it modulates neurotransmit
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G P also plays a critical role
2021-12-06

G6P also plays a critical role in regulating HK2 binding to mitochondria. Elevated levels of intracellular G6P weaken HK2 binding to mitochondria, causing the enzyme to translocate to the cytoplasm and facilitate anabolic glucose metabolism. Acidosis similarly induces HK2 translocation from mitochon
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Taken together specific antibodies and
2021-12-06

Taken together, specific sq 22 and SR-SIM used in the study helped uniquely visualize the distribution of lymphocytes and macrophages with their molecular expression in human cochleae. Using SR-SIM, we verified that resident IBA1-positive macrophages are widely distributed in human cochlea (Liu et a
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br Functional organization of postsynaptic glutamate recepto
2021-12-06

Functional organization of postsynaptic glutamate receptors Downstream effects of glutamate receptor positioning Mechanisms underlying the subsynaptic positioning of glutamate receptors Conclusions and future prospects The molecular organization of synapses is undoubtedly a critical dete
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Having shown that some of substitutions Cl CF at
2021-12-04

Having shown that some of substitutions (Cl, CF) at the 2-position of the thiophene improved rat microsomal stability, and polar groups at the 4-position of the aryl ring had a beneficial effect on stability in both human and rat microsomes, we combined these features in a new set of analogs. Methyl
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PBI is an agonist of GPR and
2021-12-03

PBI-4050 is an agonist of GPR40 and acts as an antagonist or inverse agonist of GPR84. It cannot be excluded that other targets besides GPR40 and GPR84 could be implicated in the mechanism of action of PBI-4050 and could be explored in future studies. However, the present study, and in particular th
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