The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury.

JOURNAL/nrgr/04.03/01300535-202511000-00027/figure1/v/2024-12-20T164640Z/r/image-tiff The mitogen-activated protein kinase kinase kinase kinases (MAP4Ks) signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults. Whether targeting this pathway is beneficial to brain injury remains unclear.

Screens in aging-relevant human ALS-motor neurons identify MAP4Ks as therapeutic targets for the disease.

Effective therapeutics is much needed for amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease mainly affecting motor neurons. By screening chemical compounds in human patient-derived and aging-relevant motor neurons, we identify a neuroprotective compound and show that MAP4Ks may serve as therapeutic targets for treating ALS. The lead compound broadly improves survival and function of motor neurons directly converted from human ALS patients.

Chemical screens in aging-relevant human motor neurons identify MAP4Ks as therapeutic targets for amyotrophic lateral sclerosis.

Effective therapeutics is much needed for amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease mainly affecting motor neurons. By screening chemical compounds in human patient-derived and aging-relevant motor neurons, we identify a neuroprotective compound and show that MAP4Ks may serve as therapeutic targets for treating ALS. The lead compound broadly improves survival and function of motor neurons directly converted from human ALS patients.

Natural variations in grain length 10 (GL10) regulate rice grain size.

Grain size is an important determinant of grain weight and yield in rice. Although several genes related to grain size have been identified, natural variations in these genes that affect grain size are poorly characterized. Here, we describe the grain length QTL GL10, encoding MADS56, which positively regulates grain length and grain weight.

Revisiting astrocyte to neuron conversion with lineage tracing in vivo.

In vivo cell fate conversions have emerged as potential regeneration-based therapeutics for injury and disease. Recent studies reported that ectopic expression or knockdown of certain factors can convert resident astrocytes into functional neurons with high efficiency, region specificity, and precise connectivity. However, using stringent lineage tracing in the mouse brain, we show that the presumed astrocyte-converted neurons are actually endogenous neurons.

GW10, a member of P450 subfamily regulates grain size and grain number in rice.

A quantitative trait locus GW10 is located on Chromosome 10 by map-based cloning, which encodes a P450 Subfamily protein. The GW10 regulates grain size and grain number in rice involved in the BR pathway. Grain size and grain number play extremely important roles in rice grain yield.

Disease Modeling with Human Neurons Reveals LMNB1 Dysregulation Underlying DYT1 Dystonia.

DYT1 dystonia is a hereditary neurologic movement disorder characterized by uncontrollable muscle contractions. It is caused by a heterozygous mutation in (), a gene encoding a membrane-embedded ATPase. While animal models provide insights into disease mechanisms, significant species-dependent differences exist since animals with the identical heterozygous mutation fail to show pathology.

Aging-relevant human basal forebrain cholinergic neurons as a cell model for Alzheimer's disease.

Background: Alzheimer's disease (AD) is an adult-onset mental disorder with aging as a major risk factor. Early and progressive degeneration of basal forebrain cholinergic neurons (BFCNs) contributes substantially to cognitive impairments of AD. An aging-relevant cell model of BFCNs will critically help understand AD and identify potential therapeutics.

Unconditional and conditional analysis of epistasis between tillering QTLs based on single segment substitution lines in rice.

Epistasis plays an important role in manipulating rice tiller number, but epistatic mechanism still remains a challenge. Here we showed the process of epistatic analysis between tillering QTLs. A half diallel mating scheme was conducted based on 6 single segment substitution lines and 9 dual segment pyramiding lines to allow the analysis of 4 epistatic components.

Backbone H, C and N resonance assignments of the proteasome lid subunit Rpn12 from Saccharomyces cerevisiae.

The 26S proteasome degrades selected polyubiquitinated proteins in the ubiquitin-proteasome system, which is the major pathway for programmed protein degradation in eukaryotic cells. The Saccharomyces cerevisiae Rpn12 locates in the lid of the 19S regulatory particle within the 26S proteasome and plays a role in recruiting the extrinsic ubiquitin receptor Rpn10. Rpn12 contains a N-terminal TPR (tetratrico peptide repeat)-like domain and a C-terminal WH (winged helix) domain.

Comprehensive transcriptomics and proteomics analyses of pollinated and parthenocarpic litchi (Litchi chinensis Sonn.) fruits during early development.

Litchi (Litchi chinensis Sonn.) is an important fruit that is widely cultivated in tropical and subtropical areas. In this study, we used RNA-Seq and iTRAQ technologies to compare the transcriptomes and proteomes of pollinated (polLFs) and parthenocarpic (parLFs) litchi fruits during early development (1 day, 2 days, 4 days and 6 days).

The alteration of H4-K16ac and H3-K27met influences the differentiation of neural stem cells.

The neural stem cell therapy provides a promising future for patients with central nerve system damage, thus an insight into its differentiation mechanism is urgently needed. Herein, we aimed to identify various histone modifications and reveal their impact on the differentiation of neural stem cells (NSCs) toward neurons. Firstly, we labeled primary NSCs using the stable isotope labeling with amino acids in cell culture (SILAC) technique.

Peroxiredoxin 6 Is a Crucial Factor in the Initial Step of Mitochondrial Clearance and Is Upstream of the PINK1-Parkin Pathway.

Aims: PTEN-putative kinase 1 (PINK1)-Parkin-mediated mitophagy is crucial for the clearance of damaged mitochondria. However, the mechanisms underlying PINK1-Parkin-mediated mitophagy are not fully understood. The goal of this study is to identify new regulators and to elucidate the regulatory mechanisms of mitophagy.

PGC-1α/ERRα-Sirt3 Pathway Regulates DAergic Neuronal Death by Directly Deacetylating SOD2 and ATP Synthase β.

Aims: Parkinson's disease (PD) heavily affects humans and little is known about its cause and pathogenesis. Sirtuin 3 (Sirt3) plays a key role in regulating mitochondrial dysfunction, which is the main cause of DAergic neuronal loss in PD. We investigated the mechanisms of neuroprotective role of Sirt3 in DAergic neuronal survival.

Quantitative proteomics reveals that PEA15 regulates astroglial Aβ phagocytosis in an Alzheimer's disease mouse model.

Unlabelled: Amyloid-beta (Aβ) deposition plays a crucial role in the progression of Alzheimer's disease (AD). The Aβ deposited extracellularly can be phagocytosed and degraded by surrounding activated astrocytes, but the precise mechanisms underlying Aβ clearance mediated by astrocytes remain unclear. In this study, we performed tandem mass tag-based quantitative proteomic analysis on the cerebral cortices of 5-month-old APP/PS1 double-transgenic mice.

Structure determination of human Fas apoptosis inhibitory molecule and identification of the critical residues linking the interdomain interaction to the anti-apoptotic activity.

Fas apoptosis inhibitory molecule (FAIM) is a highly conserved anti-apoptotic protein which plays important roles in cells. There are two isoforms of FAIM, of which the short isoform FAIM-S is broadly expressed in all tissues, whereas the long isoform FAIM-L is exclusively expressed in the nervous system. No structure of human FAIM has been reported to date and the detailed molecular mechanisms underlying the anti-apoptotic function of FAIM remain unknown.

Activated cyclin-dependent kinase 5 promotes microglial phagocytosis of fibrillar β-amyloid by up-regulating lipoprotein lipase expression.

Amyloid plaques are crucial for the pathogenesis of Alzheimer disease (AD). Phagocytosis of fibrillar β-amyloid (Aβ) by activated microglia is essential for Aβ clearance in Alzheimer disease. However, the mechanism underlying Aβ clearance in the microglia remains unclear.