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Gi/o protein-coupled receptors (Gi/o-GPCRs) limit β-cell insulin secretion by decreasing Ca2+ entry; however, the underlying mechanism has not been identified. Here, the authors show that Gi/o-GPCRs hyperpolarize mouse and human β-cell membrane potential by activating Na+/K+ATPases.

Rising anthropogenic CO2 levels in the atmosphere are resulting in ocean acidification which may impact coral growth rates. Here, the authors quantify the relationship between water depth and δ13C compositions of South Pacific corals from the pre-industrial era, and their results should lead to improvements in the precision of sea level reconstructions using fossil corals.

The original version of the Source Data associated with this Article included an error, in which the ‘Fiji AB d13C-Suess’ data point and the ‘TNI2 d13C-Suess Effect’ data point for the year ‘1950.5’ where incorrectly omitted from the Figure 3 tab. The missing values are ‘−0.24’ and ‘−0.64’, respectively. The HTML has been updated to include a corrected version of Source Data.

Abstract Determining the genetic architecture of Alzheimer’s disease pathologies can enhance mechanistic understanding and inform precision medicine strategies. Here, we perform a genome-wide association study of cortical tau quantified by positron emission tomography in 3046 participants from 12 independent studies. The CYP1B1-RMDN2 locus is associated with tau deposition. The most significant signal is at rs2113389, explaining 4.3% of the variation in cortical tau, while APOE4 rs429358 accounts for 3.6%. rs2113389 is associated with higher tau and faster cognitive decline. Additive effects, but no interactions, are observed between rs2113389 and diagnosis, APOE4, and amyloid beta positivity. CYP1B1 expression is upregulated in AD. rs2113389 is associated with higher CYP1B1 expression and methylation levels. Mouse model studies provide additional functional evidence for a relationship between CYP1B1 and tau deposition but not amyloid beta. These results provide insight into the genetic basis of cerebral tau deposition and support novel pathways for therapeutic development in AD.

Gi/o-coupled somatostatin or α2-adrenergic receptor activation stimulated β-cell NKA activity, resulting in islet Ca2+ fluctuations. Furthermore, intra-islet paracrine activation of β-cell Gi/o-GPCRs and NKAs by δ-cell somatostatin secretion slowed Ca2+ oscillations, which decreased insulin secretion. β-cell membrane potential hyperpolarization resulting from Gi/o-GPCR activation was dependent on NKA phosphorylation by Src tyrosine kinases. Whereas, β-cell NKA function was inhibited by cAMP-dependent PKA activity. These data reveal that NKA-mediated β-cell membrane potential hyperpolarization is the primary and conserved mechanism for Gi/o-GPCR control of electrical excitability, Ca2+ handling, and insulin secretion. Gi/o protein-coupled receptors (Gi/o-GPCRs) limit β-cell insulin secretion by decreasing Ca2+ entry; however, the underlying mechanism has not been identified. Here, the authors show that Gi/o-GPCRs hyperpolarize mouse and human β-cell membrane potential by activating Na+/K+ATPases. [ABSTRACT FROM AUTHOR]

The signal-to-noise ratio is a key consideration when selecting a magnetic resonance imaging protocol. Thermal noise is major issue, especially in high resolution functional images. Here the authors introduce a method to suppress thermal noise in functional images without losses in spatial precision, increasing the signal-to-noise ratio.

Peripheral T cell lymphomas are typically aggressive with a poor prognosis. Unlike other hematologic malignancies, the lack of target antigens to discriminate healthy from malignant cells limits the efficacy of immunotherapeutic approaches. The T cell receptor expresses one of two highly homologous chains [T cell receptor β-chain constant (TRBC) domains 1 and 2] in a mutually exclusive manner, making it a promising target. Here we demonstrate specificity redirection by rational design using structure-guided computational biology to generate a TRBC2-specific antibody (KFN), complementing the antibody previously described by our laboratory with unique TRBC1 specificity (Jovi-1) in targeting broader spectrum of T cell malignancies clonally expressing either of the two chains. This permits generation of paired reagents (chimeric antigen receptor-T cells) specific for TRBC1 and TRBC2, with preclinical evidence to support their efficacy in T cell malignancies., (© 2024. The Author(s).)