Nature Immunology, Published online: 25 September 2023; doi:10.1038/s41590-023-01606-x
On 20–23 June 2023, the 10th International γδ T cell conference was held in Lisbon, Portugal, bringing together basic, translational and clinical researchers studying γδ T cells in health and disease.Optimizing acid overproduction
Nature Chemical Biology, Published online: 25 September 2023; doi:10.1038/s41589-023-01442-y
Optimizing acid overproductionAntioxidant activity of venison subjected to in vitro cooking and gastrointestinal digestion and isolation of its 2,2‐diphenyl‐1‐picrylhydrazyl radical scavenging peptides
Abstract
Venison, a type of game meat, has several health benefits because it contains not only high protein and low fat but also bioactive peptides with several physiological properties, including antioxidative and angiotensin-converting enzyme inhibitory properties. The aim of the present study was to investigate the antioxidant activity of venison treated by in vitro cooking and gastrointestinal digestion. We subjected venison along with pork and beef to in vitro cooking and digestion and assessed their antioxidant activity via 2,2-diphenyl-1-picrylhydrazyl radical scavenging (DPPH-RS) and hydrophilic oxygen radical absorbance capacity (H-ORAC) assays. The peptide contents of all types of cooked and digested meat samples were higher than those of the untreated and cooked samples. The DPPH-RS activities and H-ORAC of digested venison, pork, and beef were increased compared with those of untreated samples. DPPH-RS activity was significantly higher in the digested venison samples than in the digested pork and beef samples. In this study, several fractions of digested venison from the chromatography exhibited DPPH-RS activity. Peptide analysis, using liquid-chromatography with tandem mass spectrometry, unveiled two peptides DIDDLELTLAK and TQTVCNFTDGALVQHQEWDGK with high DPPH-RS activities. Thus, venison is a rich source of antioxidant peptides and potentially demonstrate an antioxidation ability by digestive enzymes in vivo.
Increase of ISG15 in psoriasis lesions and its promotion of keratinocyte proliferation via the Hif‐1α signalling pathway
Abstract
Psoriasis is a frequent chronic, recurrent and immune-mediated inflammatory skin disease, whose pathogenesis remains unclear at present. The role of antiviral protein in the pathogenesis of psoriasis is the focus of current research. Interferon stimulated gene 15 (ISG15) is an important antiviral protein. In this study, the expression of ISG15 saw a significant increase through the immunohistochemical detection of imiquimod (IMQ)-induced mice. In the psoriasis cell model, a remarkable increase also occurred in the expression of ISG15. In this study, it was found that the cell cycle was blocked in G1/S conversion, and a reduction took place in the proliferation of keratinocytes and the expression of a cell cycle-related protein—cyclin D1 after the knockout of ISG15 in the psoriasis cell model. After that, messenger ribonucleic acid (mRNA) sequencing and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) analysis indicated its close association with the hypoxia inducible factor-1α (HIF-1α) signalling pathway. Western blot showed a decrease in the expression of HIF-1α and vascular endothelial growth factor C (VEGFC) after the knockout of the ISG15 gene. The rescue experiment verified that ISG15 promotes the proliferation of keratinocytes by regulating the HIF-1α signalling pathway. It was concluded that psoriasis cells and mouse models witnessed the increased expression of ISG15. In psoriasis, knocking out ISG15 inhibits the proliferation of keratinocytes and blocks the cell cycle. Besides, ISG15 promotes the proliferation of keratinocytes through the HIF-1α signalling pathway.
Changing the guard—nuclear pore complex quality control
This perspective discusses the challenges associated with nuclear pore complex (NPC) assembly and the need for quality control (QC) mechanisms that operate at various stages of an NPC's life: from QC mechanisms that keep individual nups assembly-competent prior to their incorporation in a new NPC and QC at the assembly site, to those that deal with damaged NPCs post-assembly.
The integrity of the nuclear envelope depends on the function of nuclear pore complexes (NPCs), transport channels that control macromolecular traffic between the nucleus and cytosol. The central importance of NPCs suggests the existence of quality control (QC) mechanisms that oversee their assembly and function. In this perspective, we emphasize the challenges associated with NPC assembly and the need for QC mechanisms that operate at various stages of an NPC's life. This includes cytosolic preassembly QC that helps enforce key nucleoporin–nucleoporin interactions and their ultimate stoichiometry in the NPC in addition to mechanisms that monitor aberrant fusion of the inner and outer nuclear membranes. Furthermore, we discuss whether and how these QC mechanisms may operate to sense faulty mature NPCs to facilitate their repair or removal. The so far uncovered mechanisms for NPC QC provide fertile ground for future research that not only benefits a better understanding of the vital role that NPCs play in cellular physiology but also how loss of NPC function and/or these QC mechanisms might be an input to aging and disease.
Human sphingomyelin synthase 1 generates diacylglycerol in the presence and absence of ceramide via multiple enzymatic activities
In this study, we demonstrated that sphingomyelin (SM) synthase 1 (SMS1) displayed phosphatidylcholine (PC)-specific phospholipase C (PC-PLC), phosphatidylethanolamine (PE)-PLC, and ceramide phosphoethanolamine (CPE) synthase (CPES) activities, in addition to SMS activity. Moreover, SMS1 exhibited a substrate specificity for saturated fatty acid (SFA)- or monounsaturated fatty acid (MUFA)-containing PC molecular species, but not polyunsaturated fatty acid-containing PC. It is possible that SMS1 preferably produces SFA-containing diacylglycerol (SFA-DG) independently of ceramide.
Sphingomyelin (SM) synthase 1 (SMS1), which is involved in lipodystrophy, deafness, and thrombasthenia, generates diacylglycerol (DG) and SM using phosphatidylcholine (PC) and ceramide as substrates. Here, we found that SMS1 possesses DG-generating activities via hydrolysis of PC and phosphatidylethanolamine (PE) in the absence of ceramide and ceramide phosphoethanolamine synthase (CPES) activity. In the presence of the same concentration (4.7 mol%) of PC and ceramide, the amounts of DG produced by SMS and PC-phospholipase C (PLC) activities of SMS1 were approximately 65% and 35% of total DG production, respectively. PC-PLC activity showed substrate selectivity for saturated and/or monounsaturated fatty acid-containing PC species. A PC-PLC/SMS inhibitor, D609, inhibited only SMS activity. Mn2+ inhibited only PC-PLC activity. Intriguingly, DG attenuated SMS/CPES activities. Our study indicates that SMS1 is a unique enzyme with PC-PLC/PE-PLC/SMS/CPES activities.
Knockout of the BRAP homolog in mice leads to abnormal tracheal cilia
Bombesin receptor-activated protein (BRAP) is a poorly characterized protein present in human bronchial epithelial cells. A gene knockout mouse lacking expression of the BRAP homolog exhibited abnormal tracheal cilia. Subsequent experiments revealed that BRAP may participate in the regulation of ciliogenesis by interacting with Rab-3A-interacting protein, which is implicated in cilia formation.
Both bombesin receptor-activated protein (BRAP) and its mouse homolog have been found to be expressed in bronchial epithelia but with unclear functions. Using electron microscopy combined with histological assays, we found that BRAP homolog deficiency in mice led to abnormal tracheal cilia. Rab-3A-interacting protein (Rabin8), a protein that might play a role in cilia development, was screened by yeast two-hybrid and further verified to have interaction with human BRAP by co-immunoprecipitation and pulldown assays. The expression levels of Rabin8, together with acetylated α-tubulin, a marker of cilia, were either downregulated by knockdown of BRAP or upregulated by overexpression of BRAP in cultured immortalized human bronchial epithelial cells. These results reveal a role for BRAP in airway cilia formation.
Men’s household water fetching in India: Gender inequity is associated with greater responsibility and related risks
Abstract
Introduction
Household water fetching elevates physical and emotional harms, and these are generally assumed to accrue to women due to gendered labor assignments. But even in cases like India where fetching remains a highly feminized task, there are households where the primary responsibility is assumed by men.
Methods
We test the proposition that men's responsibility for water fetching is predicted by greater gender equity, reflected in measures of wives' empowerment. We used an extremely large, nationally representative Demographic and Health Survey dataset from India (2019–2020), narrowed to only households in which spouses co-reside with off-plot water sources (N = 10 616), and applying a multinomial regression approach.
Results
In >20% of households, men are the primary fetchers. They are more likely to have primary responsibility when water is more distant, privately purchased, or transported by vehicle. Contrary to predictions, men assume greater responsibility for household water fetching as their wives' empowerment measures decrease and when they want to control their movement.
Conclusion
Married men in India sometimes assume responsibility for water fetching, but this is not explained by greater household gender equity. The findings also suggest that when men are responsible for fetching they have heightened risk of some forms of physical trauma but less relative psychological harm. Detailing why men fetch water matters for identifying and mitigating the physical and emotion harms of bearing responsibility for water labor, with implications for how gender should be conceptualized in water interventions intending to improve health and well-being.
Artificial intelligence in psoriasis: Where we are and where we are going
Abstract
Artificial intelligence (AI) is a field of computer science that involves the development of programs designed to replicate human cognitive processes and the analysis of complex data. In dermatology, which is predominantly a visual-based diagnostic field, AI has become increasingly important in improving professional processes, particularly in the diagnosis of psoriasis. In this review, we summarized current AI applications in psoriasis: (i) diagnosis, including identification, classification, lesion segmentation, lesion severity and area scoring; (ii) treatment, including prediction treatment efficiency and prediction candidate drugs; (iii) management, including e-health and preventive medicine. Key challenges and future aspects of AI in psoriasis were also discussed, in hope of providing potential directions for future studies.
Organic selenium and vitamin E for gilts and sows bred in equatorial climate
Abstract
The aim of this study was to evaluate the dietary supplementation of organic selenium (Se) and vitamin E for sows from 1st and 2nd parity order, without adiabatic cooling on physiological parameters, reproductive performance, milk composition, litter performance and blood concentrations of antioxidant enzymes. A total of 96 sows were allotted in a 4 × 2 completely factorial design, with 4 experimental groups and 2 parity orders (1st and 2nd). The experimental groups consisted of: ACCon—sows receiving adiabatic cooling and no dietary supplementation of organic Se and vitamin E; WACCon—sows without adiabatic cooling and no dietary supplementation of organic Se and vitamin E; WACSe—sows without adiabatic cooling with dietary supplementation of 0.3 mg/kg organic Se; WACSeE—sows without adiabatic cooling with dietary supplementation of 0.3 mg/kg organic Se and 90 UI of vitamin E. ACCon Sows had lower respiratory rate, rectal temperature and body surface temperature when compared to the others sows (p < 0.05). Sows without evaporative cooling had lower daily milk production and weaned litters with lower weight and average daily gain when compared to the other groups (p < 0.05). ACCon sows presented higher weaned piglets to WACSeE sows. WACSeE Sows had higher concentrations of GSH-Px when compared to other experimental groups and higher levels of SOD than sows from ACCon and WACSe. Piglets of sows from WACSeE group presented higher levels of GSH-Px and SOD when compared to the other experimental groups. ACCon sows have higher milk yield and higher litter weight than others groups. Under equatorial climate conditions, dietary supplementation of organic Se and vitamin E from first and second parity order sows does not respond efficiently on thermoregulatory physiology and performance compared to adiabatic cooling, but modulates the enzymatic antioxidant balance of sows and piglets.