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miRNAs are important regulators of differentiation, development, and function of brown and beige fat cells. In this study, we identify the role of the miR-199a/214 cluster in the regulation of brown and beige adipocyte development and thermogenesis in vitro and in vivo. We show that expression of the miR-199a/214 cluster is dramatically decreased during brown and beige adipocyte differentiation and in response to cold exposure or β-adrenergic receptor activation. The cluster levels are significantly upregulated in the adipose tissues of obese mice and human subjects. Overexpression of the miR-199a/214 cluster suppresses brown adipocyte differentiation and inhibits thermogenic gene expression and mitochondrial respiration, whereas knockdown of the cluster increases thermogenic gene expression and mitochondrial function in beige adipocytes. In addition, inhibition of the miR-199a/214 cluster promotes beiging effects in vivo. We further show that miR-199a/214 suppresses brown adipocyte differentiation and beige fat development by directly targeting PRDM16 and peroxisome PGC-1α, two key transcriptional regulators of adipose browning. Together, these observations reveal that the miR-199a/214 cluster is a key negative regulator of brown and beige fat development and thermogenesis. [ABSTRACT FROM AUTHOR]

To develop genetic markers associated with tolerance to low phosphorus, we identified candidate phosphate starvation responsive ( PSR) genes and developed their intron length polymorphism ( ILP) markers in maize on a genome-wide scale. Based on the known plant PSR genes, 161 candidate PSR genes were identified. Of these genes, 138 genes contained at least one intron and were then used to develop 606 PSR- ILP markers by designing PCR primers to the intron-flanking exonic regions. PCR evaluation was performed on 43 randomly selected PSR- ILP markers in 30 maize inbred lines. Of the primers, 88.4% amplified stable and pure products in all maize inbred lines, and 53.5% of the markers showed ILP, with PIC values ranging from 0.06 to 0.80. The result of clustering analysis of the 30 maize inbred lines, based on the polymorphism of 23 ILP markers, suggests that the ILP markers developed in this study are not only efficient for genetic diversity analysis but also potentially useful for marker assisted selection for tolerance to low phosphorus. [ABSTRACT FROM AUTHOR]

Key Message: Three computationally efficient algorithms of GP including RHBK, RHDK, and RHPK were developed in approximate genome-based kernel model. The drastically growing amount of genomic information contributes to increasing computational burden of genomic prediction (GP). In this study, we developed three computationally efficient algorithms of GP including RHBK, RHDK, and RHPK in approximate genome-based kernel model, which reduces dimension of genomic data via Nyström approximation and decreases the computational cost significantly thereby. According to the simulation study and real datasets, our three methods demonstrated predictive accuracy similar to or better than RHAPY, GBLUP, and rrBLUP in most cases. They also demonstrated a substantial reduction in computational time compared to GBLUP and rrBLUP in simulation. Due to their advanced computing efficiency, our three methods can be used in a wide range of application scenarios in the future., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Ethical approval: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Obesity is a growing global health epidemic with limited orally administered therapeutics. Serotonin (5-HT) is one neurotransmitter which remains an excellent target for new weight-loss therapies, but a gap remains in understanding the mechanisms involved in 5-HT produced in the dorsal Raphe nucleus (DRN) and its involvement in meal initiation. Using an optogenetic feeding paradigm, we showed that the 5-HT DRN ➔arcuate nucleus (ARH) circuit plays a role in meal initiation. Incorporating electrophysiology and ChannelRhodopsin-2-Assisted Circuit Mapping, we demonstrated that 5-HT DRN neurons receive inhibitory input partially from GABAergic neurons in the DRN, and the 5-HT response can be enhanced by hunger. Additionally, deletion of the GABA A receptor subunit in 5-HT neurons inhibits meal initiation with no effect on the satiation process. Finally, we identified the role of dopaminergic inputs via dopamine receptor D2 in enhancing the response to GABA-induced feeding. Thus, our results indicate that 5-HT DRN neurons are inhibited by synergistic inhibitory actions of GABA and dopamine, for the initiation of a meal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The major female ovarian hormone, 17β-estradiol (E 2 ), can alter neuronal excitability within milliseconds to regulate a variety of physiological processes. Estrogen receptor-α (ERα), classically known as a nuclear receptor, exists as a membrane-bound receptor to mediate this rapid action of E 2 , but the ionic mechanisms remain unclear. Here, we show that a membrane channel protein, chloride intracellular channel protein-1 (Clic1), can physically interact with ERα with a preference to the membrane-bound ERα. Clic1-mediated currents can be enhanced by E 2 and reduced by its depletion. In addition, Clic1 currents are required to mediate the E 2 -induced rapid excitations in multiple brain ERα populations. Further, genetic disruption of Clic1 in hypothalamic ERα neurons blunts the regulations of E 2 on female body weight balance. In conclusion, we identified the Clic1 chloride channel as a key mediator for E 2 -induced rapid neuronal excitation, which may have a broad impact on multiple neurobiological processes regulated by E 2 .

When genomic prediction is implemented in breeding maize ( Zea mays L.), it can accelerate the breeding process and reduce cost to a large extent. In this study, 11 yield-related traits of maize were used to evaluate four genomic prediction methods including rrBLUP, HEBLP|A, RF, and LightGBM. In all the 11 traits, rrBLUP had similar predictive accuracy to HEBLP|A, and so did RF to LightGBM, but rrBLUP and HEBLP|A outperformed RF and LightGBM in 8 traits. Furthermore, genomic prediction-based heterotic pattern of yield was established based on 64620 crosses of maize in Southwest China, and the result showed that one of the parent lines of the top 5% crosses came from temp-tropic or tropic germplasm, which is highly consistent with the actual situation in breeding, and that heterotic pattern (Reid+ × Suwan+) will be a major heterotic pattern of Southwest China in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiang, Xia, Li, Wei, Rong, Liu and Lan.)

Light plays an essential role in a variety of physiological processes, including vision, mood, and glucose homeostasis. However, the intricate relationship between light and an animal's feeding behavior has remained elusive. Here, we found that light exposure suppresses food intake, whereas darkness amplifies it in male mice. Interestingly, this phenomenon extends its reach to diurnal male Nile grass rats and healthy humans. We further show that lateral habenula (LHb) neurons in mice respond to light exposure, which in turn activates 5-HT neurons in the dorsal Raphe nucleus (DRN). Activation of the LHb→5-HT DRN circuit in mice blunts darkness-induced hyperphagia, while inhibition of the circuit prevents light-induced anorexia. Together, we discovered a light-responsive neural circuit that relays the environmental light signals to regulate feeding behavior in mice., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Declined memory is a hallmark of Alzheimer's disease (AD). Experiments in rodents and human postmortem studies suggest that serotonin (5-hydroxytryptamine, 5-HT) plays a role in memory, but the underlying mechanisms are unknown. Here, we investigate the role of 5-HT 2C receptor (5-HT 2C R) in regulating memory. Transgenic mice expressing a humanized HTR2C mutation exhibit impaired plasticity of hippocampal ventral CA1 (vCA1) neurons and reduced memory. Further, 5-HT neurons project to and synapse onto vCA1 neurons. Disruption of 5-HT synthesis in vCA1-projecting neurons or deletion of 5-HT 2C Rs in the vCA1 impairs neural plasticity and memory. We show that a selective 5-HT 2C R agonist, lorcaserin, improves synaptic plasticity and memory in an AD mouse model. Cumulatively, we demonstrate that hippocampal 5-HT 2C R signaling regulates memory, which may inform the use of 5-HT 2C R agonists in the treatment of dementia.

Purpose: The aims were to assess different branching patterns of segmental bronchi in the right superior lobe (RSL), as well as to investigate the anatomical diversity and sex-related variations of these branches in a large sample of the research population., Methods: 10,000 participants (5428 males, and 4,572 females, mean age 50+/-13.5 years [SD] years; age range: 3-91 years) who underwent multi-slice CT (MSCT) scans from September 2019 to December 2021 were retrospectively included. The data were applied to generate three-dimensional (3D) and virtual bronchoscopy (VB) simulations of a bronchial tree using the syngo.via post-processing workstation. Following that, the reconstructed images were interpreted to identify and categorize various bronchial patterns in the RSL. Cross-tabulation analysis and the Pearson chi-square test (χ2) were used to calculate the component ratios of bronchial branch types and determine their relevance between male and female groups., Results: Our results revealed mainly six types for the RSL bronchial tree, i.e., (B1, B2, B3, 60.70%); (B1+2, B3, 18.72%); (B2+3, B1, 6.68%); (B1+3, B2, 7.57%); (B1, B2, B3, B*, 3.19%); (B1a+B3, B1b+B2, 3.14%). There were significant sex-related differences in the proportion of bronchial branches in the RSL (P< 0.05)., Conclusion: The current study has validated the presence of segmental bronchial variations in the RSL. These findings may have significant implications for diagnosing symptomatic patients and performing particular procedures, including bronchoscopy, endotracheal intubation, and lung resection., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Vitamin D action has been linked to several diseases regulated by the brain including obesity, diabetes, autism, and Parkinson's. However, the location of the vitamin D receptor (VDR) in the brain is not clear due to conflicting reports. We found that two antibodies previously published as specific in peripheral tissues are not specific in the brain. We thus created a new knockin mouse with cre recombinase expression under the control of the endogenous VDR promoter (VDR Cre ). We demonstrated that the cre activity in the VDR Cre mouse brain (as reported by a cre-dependent tdTomato expression) is highly overlapping with endogenous VDR mRNAs. These VDR-expressing cells were enriched in multiple brain regions including the cortex, amygdala, caudate putamen, and hypothalamus among others. In the hypothalamus, VDR partially colocalized with vasopressin, oxytocin, estrogen receptor-α, and β-endorphin to various degrees. We further functionally validated our model by demonstrating that the endogenous VDR agonist 1,25-dihydroxyvitamin D activated all tested tdTomato + neurons in the paraventricular hypothalamus but had no effect on neurons without tdTomato fluorescence. Thus, we have generated a new mouse tool that allows us to visualize VDR-expressing cells and to characterize their functions., (© 2020 Wiley Periodicals LLC.)

Coix is a grass crop domesticated as early as the Neolithic era. It is still widely cultivated for both highly nutritional food and medicinal use. However, the genetic study and breeding of this crop are hindered by the lack of a sequenced genome. Here, we report de novo sequencing and assembly of the 1619-Mb genome of Coix, and annotation of 75.39% repeats and 39 629 protein-coding genes. Comparative genomics analysis showed that Coix is more closely related to sorghum than maize, but intriguingly only Coix and maize had a recent genome duplication event, which was not detected in sorghum. We further constructed a genetic map and mapped several important traits, especially the strength of hull. Selection of papery hull (thin: easy dehulling) from the stony hull (thick: difficult dehulling) in wild progenitors was a key step in Coix domestication. The papery hull makes seed easier to process and germinate. Anatomic and global transcriptome analysis revealed that the papery hull is a result of inhibition of cell division and wall biogenesis. We also successfully demonstrated that seed hull pressure resistance is controlled by two major quantitative trait loci (QTLs), which are associated with hull thickness and color, respectively. The two QTLs were further fine mapped within intervals of 250 kb and 146 kb, respectively. These resources provide a platform for evolutionary studies and will facilitate molecular breeding of this important crop., (Copyright © 2019 The Author. Published by Elsevier Inc. All rights reserved.)

Inactivating mutations in the copper transporter Atp7b result in Wilson's disease. The Atp7b -/- mouse develops hallmarks of Wilson's disease. The activity of several nuclear receptors decreased in Atp7b -/- mice, and nuclear receptors are critical for maintaining metabolic homeostasis. Therefore, we anticipated that Atp7b -/- mice would exhibit altered progression of diet-induced obesity, fatty liver, and insulin resistance. Following 10 wk on a chow or Western-type diet (40% kcal fat), parameters of glucose and lipid homeostasis were measured. Hepatic metabolites were measured by liquid chromatography-mass spectrometry and correlated with transcriptomic data. Atp7b -/- mice fed a chow diet presented with blunted body-weight gain over time, had lower fat mass, and were more glucose tolerant than wild type (WT) littermate controls. On the Western diet, Atp7b -/- mice exhibited reduced body weight, adiposity, and hepatic steatosis compared with WT controls. Atp7b -/- mice fed either diet were more insulin sensitive than WT controls; however, fasted Atp7b -/- mice exhibited hypoglycemia after administration of insulin due to an impaired glucose counterregulatory response, as evidenced by reduced hepatic glucose production. Coupling gene expression with metabolomic analyses, we observed striking changes in hepatic metabolic profiles in Atp7b -/- mice, including increases in glycolytic intermediates and components of the tricarboxylic acid cycle. In addition, the active phosphorylated form of AMP kinase was significantly increased in Atp7b -/- mice relative to WT controls. Alterations in hepatic metabolic profiles and nuclear receptor signaling were associated with improved glucose tolerance and insulin sensitivity as well as with impaired fasting glucose production in Atp7b -/- mice., Competing Interests: The authors declare no competing interest.

Background: Understanding the history of life requires that we understand the transfer of genetic material across phylogenetic boundaries. Detecting genes that were acquired by means other than vertical descent is a basic step in that process. Detection by discordant phylogenies is computationally expensive and not always definitive. Many have used easily computed compositional features as an alternative procedure. However, different compositional methods produce different predictions, and the effectiveness of any method is not well established., Results: The ability of octamer frequency comparisons to detect genes artificially seeded in cyanobacterial genomes was markedly increased by using as a training set those genes that are highly conserved over all bacteria. Using a subset of octamer frequencies in such tests also increased effectiveness, but this depended on the specific target genome and the source of the contaminating genes. The presence of high frequency octamers and the GC content of the contaminating genes were important considerations. A method comprising best practices from these tests was devised, the Core Gene Similarity (CGS) method, and it performed better than simple octamer frequency analysis, codon bias, or GC contrasts in detecting seeded genes or naturally occurring transposons. From a comparison of predictions with phylogenetic trees, it appears that the effectiveness of the method is confined to horizontal transfer events that have occurred recently in evolutionary time., Conclusions: The CGS method may be an improvement over existing surrogate methods to detect genes of foreign origin.

Human fatty acid synthase (FASN) is a homo-dimeric protein with multi-enzymatic activity responsible for the synthesis of palmitate. FASN expression has been found to be up-regulated in multiple types of human cancers and its expression correlates with poor prognosis possibly by causing treatment resistance. In this study, we tested if FASN expression is up-regulated in human pancreatic cancers and if its higher expression level in pancreatic cancers causes intrinsic resistance to gemcitabine and radiation. We found that FASN expression is significantly up-regulated in human pancreatic cancer tissues without any correlation to age, sex, race, and tumor stage. Knocking down or over-expressing FASN significantly down- or up-regulate resistance of pancreatic cancer cell lines to both gemcitabine and radiation treatments. These findings imply that the elevated FASN expression in pancreatic cancers may contribute to unsuccessful treatments of pancreatic cancers by causing intrinsic resistance to both chemotherapy and radiation therapy.

Human fatty acid synthase (FASN) is a 270-kDa cytosolic dimeric enzyme that is responsible for palmitate synthesis. FASN is slowly emerging and rediscovered as a marker for diagnosis and prognosis of human cancers. Recent studies showed that FASN is an oncogene and inhibition of FASN effectively and selectively kill cancer cells. With recent publications of the FASN crystal structure and the new development of FASN inhibitors, targeting FASN opens a new window of opportunity for metabolically combating cancers. In this article, we will review critically the recent progresses in understanding the structure, function, and the role of FASN in cancers and pharmacologically targeting FASN for human cancer treatment.