Ruminal degradation characteristics of bagasse with different fermentation treatments in the rumen of beef cattle.

This experiment aimed to study the degradation characteristics of bagasse after three fermentation treatments in beef cattle. Bagasse 1 was treated with 0.3% lactic acid bacteria (w/w). Bagasse 2 was treated with 0.3% mixed strains (Saccharomyces cerevisiae, Aspergillus niger, Aspergillus oryzae, and lactic acid bacteria at 2:1:1:1). Bagasse 3 was treated with 0.1% cellulase and 0.1% xylanase in addition to 0.3% mixed strains of bagasse 2. The dry matter (DM), crude ash (ASH), crude protein (CP), neutral detergent fiber (NDF), and acid detergent fiber (ADF) in the bagasses were determined. Compared to the control bagasse (without the strain and enzyme treatments), three fermented bagasses showed higher DM after 4 h fermentation. The CP and ASH contents in fermented bagasse 3 were the highest, while the contents of NDF and ADF in fermented bagasse 3 were the lowest among all the groups. The effective degradability of DM, CP, NDF, and ADF was highest in fermented bagasse 3 among the evaluated bagasse feed, followed by fermented bagasse 2 > fermented bagasse 1 > bagasse. Overall, fermented bagasse 3 was better than the control and other treated bagasses, thus fermented bagasse 3 is a hopeful source for ruminant diet of beef cattle.

Novel Genetic and Phenotypic Expansion in Ameliorated PUF60-Related Disorders.

Heterozygous variants in the Poly(U) Binding Splicing Factor 60kDa gene (PUF60) have been associated with Verheij syndrome, which has the key features of coloboma, short stature, skeletal abnormalities, developmental delay, palatal abnormalities, and congenital heart and kidney defects. Here, we report five novel patients from unrelated families with PUF60-related disorders exhibiting novel genetic and clinical findings with three truncating variants, one splice-site variant with likely reduced protein expression, and one missense variant. Protein modeling of the patient's missense variant in the PUF60 AlphaFold structure revealed a loss of polar bonds to the surrounding residues. Neurodevelopmental disorders were present in all patients, with variability in speech, motor, cognitive, social-emotional and behavioral features. Novel phenotypic expansions included movement disorders as well as immunological findings with recurrent respiratory, urinary and ear infections, atopic diseases, and skin abnormalities. We discuss the role of PUF60 in immunity with and without infection based on recent organismic and cellular studies. As our five patients showed less-severe phenotypes than classical Verheij syndrome, particularly with the absence of key features such as coloboma or palatal abnormalities, we propose a reclassification as PUF60-related neurodevelopmental disorders with multi-system involvement. These findings will aid in the genetic counseling of patients and families.

Hydrocarbon Generation and Expulsion Histories of the Upper Permian Longtan Formation in the Eastern Sichuan Basin, Southwest China.

The Upper Permian Longtan Formation is the main source rock of the Lower Triassic Jialingjiang Formation in the Eastern Sichuan Basin, Southwest China. However, studies of its maturity evolution and oil generation and expulsion histories are lacking, which are not conducive to the accumulation dynamics of the Jialingjiang Formation in the Eastern Sichuan Basin. Based on the study of tectono-thermal history and geochemical parameter data of the source rock, this paper uses basin modeling technology to simulate the maturity evolution and hydrocarbon generation and expulsion histories of the Upper Permian Longtan Formation in the Eastern Sichuan Basin. The results show that the Longtan Formation source rock in the Eastern Sichuan Basin entered the oil generation threshold at the middle stage of the Early Jurassic and reached the high-maturity stage in the north and central regions at the late stage of the Early Jurassic, and the maturity did not increase after the late stage of the Middle Jurassic. The source rock had the characteristic of "one-stage oil generation and one-stage oil expulsion"; the corresponding period of high oil expulsion was 182-174 Ma (the late stage of the Early Jurassic), which was later than the formation time of the trap of the Jialingjiang Formation, possibly providing oil sources for the paleo-oil reservoirs of the Jialingjiang Formation. The results are of great significance to the gas accumulation process and exploration decision-making in the Eastern Sichuan Basin.

Ultrasonographic classification of 26 cases of fetal umbilical-portal-systemic venous shunts and the correlations with fetal chromosomal abnormalities.

OBJECTIVE: To investigate the ultrasonographic classification of fetal umbilical-portal-systemic venous shunts (UPSVS) and the correlations with fetal chromosomal abnormalities. METHODS: We retrospectively analyzed the ultrasound characteristics and the corresponding chromosomal abnormalities of 26 cases of fetal UPSVS prenatally diagnosed. RESULTS: A total of 26 fetuses diagnosed as UPSVS were included, including four cases of type I UPSVS, ten of type II, three of type IIIA, and nine of type IIIB. Four cases of type I were all complicated by fetal heart enlargement and heart insufficiency, of which one case had multiple malformations, and all four cases terminated pregnancies. Six of ten cases of type II terminated pregnancies, including four of Down's syndrome, one of twin reversed arterial perfusion sequence, one of fetal edema but with normal copy number variation (CNV) by chorionic villus sampling. The other four of ten cases were isolated type II with normal chromosomes, which were delivered at full term and were normal in growth and development when followed up 34 months after birth. Three cases of type IIIA all terminated pregnancies, of which one had multiple malformations, one had right multicystic dysplastic kidney, and one had fetal heart enlargement and heart failure. Among nine of type IIIB, seven with chromosomal abnormalities and/ or complicated malformations terminated pregnancies, and two with isolated type IIIB and normal chromosomes were delivered at full term, and were normal in growth and development (one was followed up to 33 months after birth and the other 20 months after birth). CONCLUSION: Fetal UPSVS can be clearly diagnosed and typed by prenatal ultrasonography. Fetal prognosis is determined by the types of UPSVS and complicated malformations and/ or chromosomal abnormalities. The probability of fetal chromosomal abnormalities in UPSVS fetuses is related to the ultrasonographic classification.

Ageing-associated changes in transcriptional elongation influence longevity.

Physiological homeostasis becomes compromised during ageing, as a result of impairment of cellular processes, including transcription and RNA splicing1-4. However, the molecular mechanisms leading to the loss of transcriptional fidelity are so far elusive, as are ways of preventing it. Here we profiled and analysed genome-wide, ageing-related changes in transcriptional processes across different organisms: nematodes, fruitflies, mice, rats and humans. The average transcriptional elongation speed (RNA polymerase II speed) increased with age in all five species. Along with these changes in elongation speed, we observed changes in splicing, including a reduction of unspliced transcripts and the formation of more circular RNAs. Two lifespan-extending interventions, dietary restriction and lowered insulin-IGF signalling, both reversed most of these ageing-related changes. Genetic variants in RNA polymerase II that reduced its speed in worms5 and flies6 increased their lifespan. Similarly, reducing the speed of RNA polymerase II by overexpressing histone components, to counter age-associated changes in nucleosome positioning, also extended lifespan in flies and the division potential of human cells. Our findings uncover fundamental molecular mechanisms underlying animal ageing and lifespan-extending interventions, and point to possible preventive measures.

mTORC1 signaling pathway regulates tooth repair.

Tooth germ injury can lead to abnormal tooth development and even tooth loss, affecting various aspects of the stomatognathic system including form, function, and appearance. However, the research about tooth germ injury model on cellular and molecule mechanism of tooth germ repair is still very limited. Therefore, it is of great importance for the prevention and treatment of tooth germ injury to study the important mechanism of tooth germ repair by a tooth germ injury model. Here, we constructed a Tg(dlx2b:Dendra2-NTR) transgenic line that labeled tooth germ specifically. Taking advantage of the NTR/Mtz system, the dlx2b+ tooth germ cells were depleted by Mtz effectively. The process of tooth germ repair was evaluated by antibody staining, in situ hybridization, EdU staining and alizarin red staining. The severely injured tooth germ was repaired in several days after Mtz treatment was stopped. In the early stage of tooth germ repair, the expression of phosphorylated 4E-BP1 was increased, indicating that mTORC1 is activated. Inhibition of mTORC1 signaling in vitro or knockdown of mTORC1 signaling in vivo could inhibit the repair of injured tooth germ. Normally, mouse incisors were repaired after damage, but inhibition/promotion of mTORC1 signaling inhibited/promoted this repair progress. Overall, we are the first to construct a stable and repeatable repair model of severe tooth germ injury, and our results reveal that mTORC1 signaling plays a crucial role during tooth germ repair, providing a potential target for clinical treatment of tooth germ injury.

The dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation.

Netrin-1 is a bifunctional chemotropic guidance cue that plays key roles in diverse cellular processes including axon pathfinding, cell migration, adhesion, differentiation, and survival. Here, we present a molecular understanding of netrin-1 mediated interactions with glycosaminoglycan chains of diverse heparan sulfate proteoglycans (HSPGs) and short heparin oligosaccharides. Whereas interactions with HSPGs act as platform to co-localise netrin-1 close to the cell surface, heparin oligosaccharides have a significant impact on the highly dynamic behaviour of netrin-1. Remarkably, the monomer-dimer equilibrium of netrin-1 in solution is abolished in the presence of heparin oligosaccharides and replaced with highly hierarchical and distinct super assemblies leading to unique, yet unknown netrin-1 filament formation. In our integrated approach we provide a molecular mechanism for the filament assembly which opens fresh paths towards a molecular understanding of netrin-1 functions.

Rational Design of a Dual-Channel Fluorescent Probe for the Simultaneous Imaging of Hypochlorous Acid and Peroxynitrite in Living Organisms.

Hypochlorous acid (HOCl) and peroxynitrite (ONOO-) are two important highly reactive oxygen/nitrogen species, which commonly coexist in biosystems and play pivotal roles in many physiological and pathological processes. To investigate their function and correlations, it is urgently needed to construct chemical tools that can track the production of HOCl and ONOO- in biological systems with distinct fluorescence signals. Here, we found that the coumarin fluorescence of coumarin-benzopyrylium (CB) hydrazides (spirocyclic form) is dim, and their fluorescence properties are controlled by their benzopyran moiety via an intramolecular photo-induced electron transfer (PET) process. Based on this mechanism, we report the development of a fluorescent probe CB2-H for the simultaneous detection of HOCl and ONOO-. ONOO- can selectively oxidize the hydrazide group of CB2-H to afford the parent dye CB2 (Absmax/Emmax = 631/669 nm). In the case of HOCl, it undergoes an electrophilic attack on the benzopyran moiety of CB2-H to give a chlorinated product CB2-H-Cl, which inhibits the PET process within the probe and thus affords a turn-on fluorescence response at the coumarin channel (Absmax/Emmax = 407/468 nm). Due to the marked differences in absorption/emission wavelengths between the HOCl and ONOO- products, CB2-H enables the concurrent detection of HOCl and ONOO- at two independent channels without spectral cross-interference. CB2-H has been applied for dual-channel fluorescence imaging of endogenously produced HOCl and ONOO- in living cells and zebrafish under different stimulants. The present probe provides a useful tool for further exploring the distribution and correlation of HOCl and ONOO- in more biosystems.

Decreased spliceosome fidelity and egl-8 intron retention inhibit mTORC1 signaling to promote longevity.

Changes in splicing fidelity are associated with loss of homeostasis and aging, yet only a handful of splicing factors have been shown to be causally required to promote longevity, and the underlying mechanisms and downstream targets in these paradigms remain elusive. Surprisingly, we found a hypomorphic mutation within ribonucleoprotein RNP-6/poly(U)-binding factor 60 kDa (PUF60), a spliceosome component promoting weak 3'-splice site recognition, which causes aberrant splicing, elevates stress responses and enhances longevity in Caenorhabditis elegans. Through genetic suppressor screens, we identify a gain-of-function mutation within rbm-39, an RNP-6-interacting splicing factor, which increases nuclear speckle formation, alleviates splicing defects and curtails longevity caused by rnp-6 mutation. By leveraging the splicing changes induced by RNP-6/RBM-39 activities, we uncover intron retention in egl-8/phospholipase C ß4 (PLCB4) as a key splicing target prolonging life. Genetic and biochemical evidence show that neuronal RNP-6/EGL-8 downregulates mammalian target of rapamycin complex 1 (mTORC1) signaling to control organismal lifespan. In mammalian cells, PUF60 downregulation also potently and specifically inhibits mTORC1 signaling. Altogether, our results reveal that splicing fidelity modulates lifespan through mTOR signaling.

Machine Learning Classification of Mild Traumatic Brain Injury Using Whole-Brain Functional Activity: A Radiomics Analysis.

OBJECTIVES: To investigate the classification performance of support vector machine in mild traumatic brain injury (mTBI) from normal controls. METHODS: Twenty-four mTBI patients (15 males and 9 females; mean age, 38.88 ± 13.33 years) and 24 age and sex-matched normal controls (13 males and 11 females; mean age, 40.46 ± 11.4 years) underwent resting-state functional MRI examination. Seven imaging parameters, including amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), degree centrality (DC), voxel-mirrored homotopic connectivity (VMHC), long-range functional connectivity density (FCD), and short-range FCD, were entered into the classification model to distinguish the mTBI from normal controls. RESULTS: The ability for any single imaging parameters to distinguish the two groups is lower than multiparameter combinations. The combination of ALFF, fALFF, DC, VMHC, and short-range FCD showed the best classification performance for distinguishing the two groups with optimal AUC value of 0.778, accuracy rate of 81.11%, sensitivity of 88%, and specificity of 75%. The brain regions with the highest contributions to this classification mainly include bilateral cerebellum, left orbitofrontal cortex, left cuneus, left temporal pole, right inferior occipital cortex, bilateral parietal lobe, and left supplementary motor area. CONCLUSIONS: Multiparameter combinations could improve the classification performance of mTBI from normal controls by using the brain regions associated with emotion and cognition.

Effects of CD4+ T lymphocytes from ovariectomized mice on bone marrow mesenchymal stem cell proliferation and osteogenic differentiation.

The present study was designed to investigate the effects of T cells on the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). BMMSCs were co-cultured with CD4+ T cells that had been pretreated with anti-TNF-α or controls and were derived from ovariectomized (OVX) mice or sham control mice. MTT was used to assess the proliferative ability of BMMSCs and flow cytometry was used to analyze the BMMSC cell cycle. Following the induction of osteogenic differentiation in BMMSCs, calcium nodules were observed using alizarin red staining and alkaline phosphatase (ALP) staining. The expression levels of the osteogenesis-associated genes, runt related transcription factor 2 (Runx2) and osteocalcin (OCN) in BMMSCs were quantified using reverse transcription-quantitative PCR and western blotting. Osteogenesis-related signaling pathways, including ERK, JNK and p38 MAPK were also examined by western blotting. BMMSCs co-cultured with CD4+ T cells from OVX mice exhibited reduced proliferative ability compared with sham mice and the cell cycle was arrested at the G2/M phase. Additionally, BMMSCs co-cultured with CD4+ T cells from OVX mice presented with reduced levels of osteogenic differentiation and lower ALP activity, less calcium deposition and reduced expression of Runx2 and OCN compared with sham mice. The reduced levels of proliferation and osteogenic differentiation of BMMSCs induced by CD4+ T cells were not seen when the T cells were had been pretreated with anti-TNF-α. The results indicated that CD4+ T cells from OVX mice inhibited the proliferation and osteogenic differentiation of BMMSCs by producing high levels of TNF-α and may provide a novel insight into the dysfunction of BMMSCs caused by estrogen deficiency.

Two Nanometer-Sized High-Nuclearity Homometallic Bromide Clusters (M26Br38)12- (M = Cu, Ag): Syntheses, Crystal Structures, and Efficient Adsorption Properties.

The spontaneous formation of discrete spherical nanosized molecules is ubiquitous in nature; however, the actual structural imitation of such high-symmetry polyhedra from the edge sharing of regular polygons has still proved to be elusive. Herein, two high-nuclearity metal clusters, namely (TTB)4·M26Br38 (M = Cu (1), Ag (2), TTB·Br3 = 1, 3, 5-tris(triethylammoniomethyl)benzene tribromide), have been rationally and solvothermally synthesized and structurally characterized. Single-crystal X-ray analysis confirmed that 1 has I4̅3m symmetry with a (Cu25Br34)12- anion shell enwrapping a CuBr4 tetrahedron and 2 has I4̅3m symmetry with a [Ag26Br34]12- anion shell enwrapping a Br4 pyramid. The diffuse-reflectance UV-vis measurements showed that both compounds possess proper semiconductor behaviors with tunable band gaps of 1.87 eV for 1 and 1.90 eV for 2. Interestingly, all the samples feature distinct adsorption speed and compound 1 shows good adsorption activity for methyl orange (MO) under the same reaction conditions. The effects of pH, temperature, and cyclicity on dye adsorption, together with the thermal stabilities and luminescence properties of the compounds, were also studied. From the cyclic adsorption of compound 1 to the anionic dye MO, it was found that the adsorption of MO was good over three cycles, and the third adsorption rate was still 93.90%.

Evolutionarily conserved regulation of immunity by the splicing factor RNP-6/PUF60.

Splicing is a vital cellular process that modulates important aspects of animal physiology, yet roles in regulating innate immunity are relatively unexplored. From genetic screens in C. elegans, we identified splicing factor RNP-6/PUF60 whose activity suppresses immunity, but promotes longevity, suggesting a tradeoff between these processes. Bacterial pathogen exposure affects gene expression and splicing in a rnp-6 dependent manner, and rnp-6 gain and loss-of-function activities reveal an active role in immune regulation. Another longevity promoting splicing factor, SFA-1, similarly exerts an immuno-suppressive effect, working downstream or parallel to RNP-6. RNP-6 acts through TIR-1/PMK-1/MAPK signaling to modulate immunity. The mammalian homolog, PUF60, also displays anti-inflammatory properties, and its levels swiftly decrease after bacterial infection in mammalian cells, implying a role in the host response. Altogether our findings demonstrate an evolutionarily conserved modulation of immunity by specific components of the splicing machinery.

Promoter hypermethylation of PIWI/piRNA pathway genes associated with diminished pachytene piRNA production in bovine hybrid male sterility.

Hybrid male sterility (HMS) is a postzygotic reproductive isolation mechanism that enforces speciation. A bovine example of HMS is the yattle (also called dzo), an interspecies hybrid of taurine cattle (Bos taurus) and yak (Bos grunniens). The molecular mechanisms underlying HMS of yattle are not well understood. Epigenetic modifications of DNA methylation and P-element induced wimpy testis (PIWI)-interacting RNA (piRNAs) are important regulators in spermatogenesis. In this study, we investigated DNA methylation patterns and piRNA expression in adult testes in hybrid infertile yattle bulls and fertile cattle and yak bulls using whole genome bisulphite-seq and small RNA-seq. Promoter hypermethylation in yattle were associated with DNA methylation involved in gamete generation, piRNA metabolic processes, spermatogenesis, and spermatid development (P < 2.6 × 10-5). Male infertility in yattle was associated with the promoter hypermethylation-associated silencing of PIWI/piRNA pathway genes including PIWIL1, DDX4, PLD6, MAEL, FKBP6, TDRD1 and TDRD5. The downstream effects of silencing these genes were diminished production of 29- to 31- nucleotide pachytene piRNAs in yattle testes. Hypermethylation events at transposable element loci (LINEs, SINEs, and LTRs) were found in yattle. LINE-derived prepachytene piRNAs increased and SINE-derived prepachytene piRNAs were reduced in yattle testes. Our data suggests that DNA methylation affects the PIWI/piRNA pathway and is involved in gene expression and pachytene piRNA production during spermatogenesis in bovine HMS. DNA hypermethylation and disruption of piRNA production contributed to unsuccessful germ cell development that may drive bovine HMS.

Michael Addition/S,N-Intramolecular Rearrangement Sequence Enables Selective Fluorescence Detection of Cysteine and Homocysteine.

Acrylate has been widely used as the recognition unit for Cys fluorescent probes. Despite this widespread use, a potential drawback of this probe type is that the ester linkage between the fluorophore and acryloyl recognition unit is liable to be hydrolyzed by abundant esterase in the cytosol, thus affording a high background signal. To solve this problem, we herein put forward a new strategy to construct a selective fluorescent probe for cysteine (Cys)/homocysteine (Hcy) with propynamide as the recognition moiety. The free probe CPA displays weakly fluorescent emission in aqueous media because of the donor-excited photoinduced electron transfer (d-PET) process within the molecule. The Michael addition of Cys (or Hcy) thiols to the conjugated alkyne of CPA gives the expected ß-sulfido-α,ß-unsaturated amides (1a/1b), which subsequently undergo an intramolecular S,N rearrangement, yielding ß-amino-α,ß-unsaturated amides (2a/2b) as the final products. The above cascade reaction results in the blockage of d-PET within CPA, thus affording a dramatic fluorescence enhancement at 495 nm. The involvement of the sulfhydryl and the adjacent amino groups in the sensing process renders CPA high selectivity for Cys/Hcy over glutathione as well as other amino acids. The probe has been successfully applied to image Cys in different cell lines. Further, CPA shows two-photon fluorescence properties, and its ability to monitor Cys in deep tissues has been demonstrated by using two-photon microscopy.

Effect of reduced energy density of close-up diets on metabolites, lipolysis and gluconeogenesis in Holstein cows.

OBJECTIVE: An experiment was conducted to determine the effect of reduced energy density of close-up diets on metabolites, lipolysis and gluconeogenesis in cows during the transition period. METHODS: Thirty-nine Holstein dry cows were blocked and assigned randomly to three groups, fed a high energy density diet (HD, 1.62 Mcal of net energy for lactation [NEL]/kg dry matter [DM]), a medium energy density diet (MD, 1.47 Mcal NEL/kg DM), or a low energy density diet (LD, 1.30 Mcal NEL/kg DM) prepartum; they were fed the same lactation diet to 28 days in milk (DIM). All the cows were housed in a free-stall barn and fed ad libitum. RESULTS: The reduced energy density diets decreased the blood insulin concentration and increased nonesterified fatty acids (NEFA) concentration in the prepartum period (p<0.05). They also increased the concentrations of glucose, insulin and glucagon, and decreased the concentrations of NEFA and ß-hydroxybutyrate during the first 2 weeks of lactation (p<0.05). The plasma urea nitrogen concentration of both prepartum and postpartum was not affected by dietary energy density (p>0.05). The dietary energy density had no effect on mRNA abundance of insulin receptors, leptin and peroxisome proliferator-activated receptor-γ in adipose tissue, and phosphoenolpyruvate carboxykinase, carnitine palmitoyltransferase-1 and peroxisome proliferator-activated receptor-α in liver during the transition period (p>0.05). The HD cows had higher mRNA abundance of hormone-sensitive lipase at 3 DIM compared with the MD cows and LD cows (p = 0.001). The mRNA abundance of hepatic pyruvate carboxykinase at 3 DIM tended to be increased by the reduced energy density of the close-up diets (p = 0.08). CONCLUSION: The reduced energy density diet prepartum was effective in controlling adipose tissue mobilization and improving the capacity of hepatic gluconeogenesis postpartum.

Preliminary Evidence of Sex Differences in Cortical Thickness Following Acute Mild Traumatic Brain Injury.

The main objective of this study was to evaluate sex differences in cortical thickness after acute mild traumatic brain injury (mTBI) and its associations with clinical outcomes. Thirty-two patients with mTBI at acute phase (2.4 ± 1.3 days post-injury) and 30 healthy controls were enrolled. All the participants underwent comprehensive neurocognitive assessments and MRI to assess cortical thickness. Significant sex differences were determined by using variance analysis of factorial design. Relations between the cortical thickness and clinical assessments were measured with the Spearman Correlation. Results revealed that patients with mTBI had significantly reduced cortical thickness in the left entorhinal cortex while increased cortical thickness in the left precuneus cortex and right lateral occipital cortex, compared with healthy controls. The interaction effect of the group × sex on cortical thickness was significant. Female patients had significant thicker cortical thickness in the left caudal anterior cingulate cortex (ACC) than male patients and had higher scores on Posttraumatic stress disorder Checklist-Civilian Version (PCL-C). Spearman correlational analysis showed a significantly positive correlations between the cortical thickness of the left caudal ACC and PCL-C ratings in female patients. Sex differences in cortical thickness support its potential as a neuroimaging phenotype for investigating the differences in clinical profiles of mild TBI between women and men.

Decoding the intensity of sensory input by two glutamate receptors in one C. elegans interneuron.

How neurons are capable of decoding stimulus intensity and translate this information into complex behavioral outputs is poorly defined. Here, we demonstrate that the C. elegans interneuron AIB regulates two types of behaviors: reversal initiation and feeding suppression in response to different concentrations of quinine. Low concentrations of quinine are decoded in AIB by a low-threshold, fast-inactivation glutamate receptor GLR-1 and translated into reversal initiation. In contrast, high concentrations of quinine are decoded by a high-threshold, slow-inactivation glutamate receptor GLR-5 in AIB. After activation, GLR-5 evokes sustained Ca2+ release from the inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ stores and triggers neuropeptide secretion, which in turn activates the downstream neuron RIM and inhibits feeding. Our results reveal that distinct signal patterns in a single interneuron AIB can encode differential behavioral outputs depending on the stimulus intensity, thus highlighting the importance of functional mapping of information propagation at the single-neuron level during connectome construction.

The role of insula-cerebellum connection underlying aversive regulation with acupuncture.

Acupuncture at pericardium 6 (PC6) shows a consistently positive efficacy in nausea response suggested by consensus expert guidelines. Nausea encompasses aversive symptom as well as strong emotional components. Disgust is a subjective emotion of uneasy commonly accompanying with a physiological response that is accompanied by strong visceral sensations (e.g., nausea). Understanding the brain circuitry by which acupuncture influences the disgust emotion may further elucidate the modulation effect of acupuncture on aversive experience. In the present study, a well-established aversive conditioning model on healthy subjects was combined with acupuncture intervention at PC6, as well as different acupoints (both local PC7 and distant GB37) as separate controls, to investigate the brain network involved aversive regulation with acupuncture; 48 healthy subjects were enrolled and randomized into four parallel groups: group 1 received disgust-induced (DI) stimuli only; groups 2, 3, and 4 received acupuncture at three single acupoints separately prior to the DI. Disgust sensations were rated at baseline and following disgust stimuli. Acupuncture PC6 can induce significant attenuations in disgust sensations than that of no intervention and acupuncture at other acupoints. Neuroimaging further showed that increased causal interaction strength between the cerebellum (nodulus) and insula can predict greater attenuations in aversive experiences. We also found evidence for radical reorganizations of local stronger casual interaction patterns to disgust-induced brain responses targeted by acupuncture at different acupoints. This study provided the brain substrate for acupuncture on aversion modulation. The coupling between the cerebellum (nodulus) and insula supported interoception system and vestibular control which provided the specific neural basis.

AIM interneurons mediate feeding suppression through the TYRA-2 receptor in C. elegans.

Feeding behavior is the most fundamental behavior in C. elegans. Our previous results have dissected the central integration circuit for the regulation of feeding, which integrates opposing sensory inputs and regulates feeding behavior in a nonlinear manner. However, the peripheral integration that acts downstream of the central integration circuit to modulate feeding remains largely unknown. Here, we find that a Gαi/o-coupled tyramine receptor, TYRA-2, is involved in peripheral feeding suppression. TYRA-2 suppresses feeding behavior via the AIM interneurons, which receive tyramine/octopamine signals from RIM/RIC neurons in the central integration circuit. Our results reveal previously unidentified roles for the receptor TYRA-2 and the AIM interneurons in feeding regulation, providing a further understanding of how biogenic amines tyramine and octopamine regulate feeding behavior.