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Nature Communications Jul 2023Experiences have been shown to modulate behavior and physiology of future generations in some contexts, but there is limited evidence for inheritance of associative...
Experiences have been shown to modulate behavior and physiology of future generations in some contexts, but there is limited evidence for inheritance of associative memory in different species. Here, we trained C. elegans nematodes to associate an attractive odorant with stressful starvation conditions and revealed that this associative memory was transmitted to the F1 progeny who showed odor-evoked avoidance behavior. Moreover, the F1 and the F2 descendants of trained animals exhibited odor-evoked cellular stress responses, manifested by the translocation of DAF-16/FOXO to cells' nuclei. Sperm, but not oocytes, transmitted these odor-evoked cellular stress responses which involved H3K9 and H3K36 methylations, the small RNA pathway machinery, and intact neuropeptide secretion. Activation of a single chemosensory neuron sufficed to induce a serotonin-mediated systemic stress response in both the parental trained generation and in its progeny. Moreover, inheritance of the cellular stress responses increased survival chances of the progeny as exposure to the training odorant allowed the animals to prepare in advance for an impending adversity. These findings suggest that in C. elegans associative memories and cellular changes may be transferred across generations.
Topics: Animals; Male; Caenorhabditis elegans; Semen; Caenorhabditis elegans Proteins; Neuropeptides; Cell Nucleus
PubMed: 37454110
DOI: 10.1038/s41467-023-39804-8 -
Food Research International (Ottawa,... Aug 2023Many healthy people suffer from milk-related gastrointestinal discomfort (GID) despite not being lactose intolerant; the mechanisms underpinning such condition are...
Many healthy people suffer from milk-related gastrointestinal discomfort (GID) despite not being lactose intolerant; the mechanisms underpinning such condition are unknown. This study aimed to explore milk protein digestion and related physiological responses (primary outcome), gut microbiome and gut permeability in 19 lactose-tolerant healthy nonhabitual milk consumers [NHMCs] reporting GID after consuming cow milk compared to 20 habitual milk consumers [HMCs] without GID. NHMCs and HMCs participated in a milk-load (250 mL) test, underwent blood sample collection at 6 time points over 6 h after milk consumption and collected urine samples and GID self-reports over 24 h. We measured the concentrations of 31 milk-derived bioactive peptides (BAPs), 20 amino acids, 4 hormones, 5 endocannabinoid system mediators, glucose and the dipeptidyl peptidase-IV (DPPIV) activity in blood and indoxyl sulfate in urine samples. Subjects also participated in a gut permeability test and delivered feces sample for gut microbiome analysis. Results showed that, compared to HMCs, milk consumption in NHMCs, along with GID, elicited a slower and lower increase in circulating BAPs, lower responses of ghrelin, insulin, and anandamide, a higher glucose response and serum DPPIV activity. The gut permeability of the two groups was similar, while the habitual diet, which was lower in dairy products and higher in the dietary-fibre-to-protein ratio in NHMCs, possibly shaped the gut microbiome; NHMCs exhibited lower abundance of Bifidobacteria, higher abundance of Prevotella and lower abundance of protease-coding genes, which may have reduced protein digestion, as evidenced by lower urinary excretion of indoxyl sulfate. In conclusion, the findings showed that a less efficient digestion of milk proteins, supported by a lower proteolytic capability of the gut microbiome, may explain GID in healthy people after milk consumption.
Topics: Animals; Cattle; Female; Humans; Milk; Milk Proteins; Proteolysis; Gastrointestinal Microbiome; Healthy Volunteers; Indican; Lactose
PubMed: 37316045
DOI: 10.1016/j.foodres.2023.112953 -
FASEB Journal : Official Publication of... Jul 2023The ion channels in sperm tail play an important role in triggering key physiological reactions, e.g., progressive motility, hyperactivation, required for successful... (Review)
Review
The ion channels in sperm tail play an important role in triggering key physiological reactions, e.g., progressive motility, hyperactivation, required for successful fertilization. Among them, CatSper and KSper have been shown to be important ion channels for the transport of Ca and K . Moreover, the voltage-gated proton channel Hv1, the sperm-specific sodium-hydrogen exchanger (sNHE), the epithelial sodium channel (ENaC), members of the temperature-sensitive TRP channel family, and the cystic fibrosis transmembrane regulator (CFTR) are also found in the flagellum. This review focuses on the latest advances in ion channels located at the flagellum, describes how they affect sperm physiological function, and summarizes some primary mutual regulation mechanism between ion channels, including PH, membrane potential, and cAMP. These ion channels may be promising targets for clinical application in infertility.
Topics: Humans; Male; Sperm Tail; Calcium Channels; Semen; Spermatozoa; Ion Transport; Sperm Motility
PubMed: 37352114
DOI: 10.1096/fj.202300756R -
Animal Biotechnology Dec 2023Colostrum contains large number of nutrients that promote the growth, differentiation, and biological functions for goat kids early somatic cells, which is crucial to... (Review)
Review
Colostrum contains large number of nutrients that promote the growth, differentiation, and biological functions for goat kids early somatic cells, which is crucial to meet the nutritional demands, immune function, and the health of goat kids later growth. Great attention has been given not only to nutritional ingredient differences between colostrum and normal milk, but also to function differences, and their effect on the physical and sensory properties of goat kid's growth performance and health status. This paper reviews the research progress of goat colostrum in recent years, mainly including the colostrum yield, components, i.e., proteins, lactose, and immunoglobulin, as well as the influence factor, i.e., number of lactation and littler size, nutrition during the gestation, and breeding environment. In addition, this review aims to summarize the synthesis and secretion mechanisms, and the digestion and absorption mechanism of goat colostrum. We conclude that even though the composition and physicochemical properties of goat colostrum are highly dynamic and variable, and the digestion and absorption mechanism has not been made fully clear until now, direct feed microbial (DFM) may be a promising alternative for improving the quality of colostrum that should be further explored for their practical usage.
Topics: Pregnancy; Female; Animals; Colostrum; Goats; Milk; Lactation
PubMed: 37039778
DOI: 10.1080/10495398.2023.2199500 -
Cellular & Molecular Biology Letters Jul 2023Sebaceous glands (SGs) synthesize and secret sebum to protect and moisturize the dermal system via the complicated endocrine modulation. Dysfunction of SG are usually...
BACKGROUND
Sebaceous glands (SGs) synthesize and secret sebum to protect and moisturize the dermal system via the complicated endocrine modulation. Dysfunction of SG are usually implicated in a number of dermal and inflammatory diseases. However, the molecular mechanism behind the differentiation, development and proliferation of SGs is far away to fully understand.
METHODS
Herein, the rat volar and mammary tissues with abundant SGs from female SD rats with (post-natal day (PND)-35) and without puberty onset (PND-25) were arrested, and conducted RNA sequencing. The protein complex of Neuropeptide Y receptor Y2 (NPY2R)/NPY5R/Nuclear factor of activated T cells 1 (NFATc1) was performed by immunoprecipitation, mass spectrum and gel filtration. Genome-wide occupancy of NFATc1 was measured by chromatin immunoprecipitation sequencing. Target proteins' expression and localization was detected by western blot and immunofluorescence.
RESULTS
NPY2R gene was significantly up-regulated in volar and mammary SGs of PND-25. A special protein complex of NPY2R/NPY5R/NFATc1 in PND-25. NFATc1 was dephosphorylated and activated, then localized into nucleus to exert as a transcription factor in volar SGs of PND-35. NFATc1 was especially binding at enhancer regions to facilitate the distal SG and sebum related genes' transcription. Dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) contributed to NFATc1 phosphorylation in PND-25, and inactivated of DYRK1A resulted in NFATc1 dephosphorylation and nuclear localization in PND-35.
CONCLUSIONS
Our findings unmask the new role of NPY2R/NFATc1/DYRK1A in pubertal SG, and are of benefit to advanced understanding the molecular mechanism of SGs' function after puberty, and provide some theoretical basis for the treatment of acne vulgaris from the perspective of hormone regulation.
Topics: Animals; Female; Rats; Acne Vulgaris; NFI Transcription Factors; Rats, Sprague-Dawley; Sebaceous Glands; Sebum; Dyrk Kinases
PubMed: 37501148
DOI: 10.1186/s11658-023-00467-4 -
The American Journal of Pathology Oct 2023Stress response pathways are crucial for cells to adapt to physiological and pathologic conditions. Increased transcription and translation in response to stimuli place... (Review)
Review
Stress response pathways are crucial for cells to adapt to physiological and pathologic conditions. Increased transcription and translation in response to stimuli place a strain on the cell, necessitating increased amino acid supply, protein production and folding, and disposal of misfolded proteins. Stress response pathways, such as the unfolded protein response (UPR) and the integrated stress response (ISR), allow cells to adapt to stress and restore homeostasis; however, their role and regulation in pathologic conditions, such as hepatic fibrogenesis, are unclear. Liver injury promotes fibrogenesis through activation of hepatic stellate cells (HSCs), which produce and secrete fibrogenic proteins to promote tissue repair. This process is exacerbated in chronic liver disease, leading to fibrosis and, if unchecked, cirrhosis. Fibrogenic HSCs exhibit activation of both the UPR and ISR, due in part to increased transcriptional and translational demands, and these stress responses play important roles in fibrogenesis. Targeting these pathways to limit fibrogenesis or promote HSC apoptosis is a potential antifibrotic strategy, but it is limited by our lack of mechanistic understanding of how the UPR and ISR regulate HSC activation and fibrogenesis. This article explores the role of the UPR and ISR in the progression of fibrogenesis, and highlights areas that require further investigation to better understand how the UPR and ISR can be targeted to limit hepatic fibrosis progression.
Topics: Humans; Hepatic Stellate Cells; Liver Cirrhosis; Unfolded Protein Response; Fibrosis; Proteins
PubMed: 37422148
DOI: 10.1016/j.ajpath.2023.06.006 -
Islets Dec 2023The pancreatic β cell synthesizes, packages, and secretes insulin in response to glucose-stimulation to maintain blood glucose homeostasis. Under diabetic conditions, a...
The pancreatic β cell synthesizes, packages, and secretes insulin in response to glucose-stimulation to maintain blood glucose homeostasis. Under diabetic conditions, a subset of β cells fail and lose expression of key transcription factors (TFs) required for insulin secretion. Among these TFs is Pancreatic and duodenal homeobox 1 (PDX1), which recruits a unique subset of transcriptional coregulators to modulate its activity. Here we describe a novel interacting partner of PDX1, the Staphylococcal Nuclease and Tudor domain-containing protein (SND1), which has been shown to facilitate protein-protein interactions and transcriptional control through diverse mechanisms in a variety of tissues. PDX1:SND1 interactions were confirmed in rodent β cell lines, mouse islets, and human islets. Utilizing CRISPR-Cas9 gene editing technology, we deleted from the mouse β cell lines, which revealed numerous differentially expressed genes linked to insulin secretion and cell proliferation, including limited expression of . We observed deficient β cell lines had reduced cell expansion rates, GLP1R protein levels, and limited cAMP accumulation under stimulatory conditions, and further show that acute ablation of impaired insulin secretion in rodent and human β cell lines. Lastly, we discovered that PDX1:SND1 interactions were profoundly reduced in human β cells from donors with type 2 diabetes (T2D). These observations suggest the PDX1:SND1 complex formation is critical for controlling a subset of genes important for β cell function and is targeted in diabetes pathogenesis.
Topics: Animals; Humans; Mice; Diabetes Mellitus, Type 2; Endonucleases; Gene Expression; Gene Expression Regulation; Homeodomain Proteins; Insulin; Insulin-Secreting Cells; Trans-Activators; Transcription Factors; Tudor Domain
PubMed: 37838950
DOI: 10.1080/19382014.2023.2267725 -
Journal of Prosthodontics : Official... Dec 2023To provide a detailed overview of the fundamentals of saliva constituents and production. The review outlines the clinical manifestations as a consequence of salivary... (Review)
Review
PURPOSE
To provide a detailed overview of the fundamentals of saliva constituents and production. The review outlines the clinical manifestations as a consequence of salivary gland dysfunction and management strategies for patients with salivary gland dysfunction. Prosthodontic implications of saliva and salivary gland dysfunction are presented.
MATERIALS AND METHODS
English-language literature relating to saliva constituents, physiologic saliva production, clinical manifestations secondary to salivary gland dysfunction, salivary biomarkers, and management strategies were retrieved via electronic search. Relevant articles were summarized for this manuscript with a view toward providing pragmatic information.
RESULTS
Saliva is produced by three pairs of major and minor salivary glands. The major salivary glands, namely, the parotid, submandibular, and sublingual glands, contribute approximately 90% of saliva production. Saliva contains serous and mucinous secretions produced by different types of cells within salivary glands. Parasympathetic and sympathetic fibers innervate the major salivary glands, and upon stimulation, the parasympathetic innervation increases serous secretions, while the sympathetic innervation increases protein secretion. Stimulated saliva is mainly derived from the parotid glands which are composed of serous acini, while unstimulated saliva is mainly derived from the submandibular glands which are composed of mixed seromucous acini. As major salivary glands contribute the most to salivary flow, local or systemic factors influencing those glands can disrupt saliva production resulting in clinically significant oral manifestations.
CONCLUSION
This review provides a fundamental overview of saliva production. In addition, the review highlights the various clinical manifestations secondary to salivary gland dysfunction, explores salivary biomarkers for screening of systemic diseases, discusses management strategies for patients with salivary gland dysfunction, and outlines the prosthodontic implications of saliva and salivary gland dysfunction.
Topics: Humans; Saliva; Prosthodontics; Salivary Glands; Parotid Gland; Biomarkers
PubMed: 37302138
DOI: 10.1111/jopr.13725 -
PeerJ 2023The crown-of-thorns starfish (COTS; ) is a slow-moving corallivore protected by an extensive array of long, sharp toxic spines. Envenomation can result in nausea,...
BACKGROUND
The crown-of-thorns starfish (COTS; ) is a slow-moving corallivore protected by an extensive array of long, sharp toxic spines. Envenomation can result in nausea, numbness, vomiting, joint aches and sometimes paralysis. Small molecule saponins and the plancitoxin proteins have been implicated in COTS toxicity.
METHODS
Brine shrimp lethality assays were used to confirm the secretion of spine toxin biomolecules. Histological analysis, followed by spine-derived proteomics helped to explain the source and identity of proteins, while quantitative RNA-sequencing and phylogeny confirmed target gene expression and relative conservation, respectively.
RESULTS
We demonstrate the lethality of COTS spine secreted biomolecules on brine shrimp, including significant toxicity using aboral spine semi-purifications of >10 kDa ( > 0.05, 9.82 µg/ml), supporting the presence of secreted proteins as toxins. Ultrastructure observations of the COTS aboral spine showed the presence of pores that could facilitate the distribution of secreted proteins. Subsequent purification and mass spectrometry analysis of spine-derived proteins identified numerous secretory proteins, including plancitoxins, as well as those with relatively high gene expression in spines, including phospholipase A2, protease inhibitor 16-like protein, ependymin-related proteins and those uncharacterized. Some secretory proteins (, vitellogenin and deleted in malignant brain tumor protein 1) were not highly expressed in spine tissue, yet the spine may serve as a storage or release site. This study contributes to our understanding of the COTS through functional, ultrastructural and proteomic analysis of aboral spines.
Topics: Animals; Proteomics; Artemia; Arthralgia; Biological Assay; Biological Transport
PubMed: 37637177
DOI: 10.7717/peerj.15689 -
Scientific Reports Apr 2024Evolution shapes protein sequences for their functions. Here, we studied the moonlighting functions of the N-linked sequon NXS/T, where X is not P, in human...
Evolution shapes protein sequences for their functions. Here, we studied the moonlighting functions of the N-linked sequon NXS/T, where X is not P, in human nucleocytosolic proteins. By comparing membrane and secreted proteins in which sequons are well known for N-glycosylation, we discovered that cyto-sequons can participate in nucleic acid binding, particularly in zinc finger proteins. Our global studies further discovered that sequon occurrence is largely proportional to protein length. The contribution of sequons to protein functions, including both N-glycosylation and nucleic acid binding, can be regulated through their density as well as the biased usage between NXS and NXT. In proteins where other PTMs or structural features are rich, such as phosphorylation, transmembrane ɑ-helices, and disulfide bridges, sequon occurrence is scarce. The information acquired here should help understand the relationship between protein sequence and function and assist future protein design and engineering.
Topics: Humans; Proteins; Glycosylation; Amino Acid Sequence; Phosphorylation; Nucleic Acids
PubMed: 38565583
DOI: 10.1038/s41598-024-57334-1