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1.
Sci Rep ; 14(1): 23523, 2024 10 09.
Article in English | MEDLINE | ID: mdl-39384849

ABSTRACT

To determine the role of internal transcribed spacer 2 (ITS2) in the identification of Spatholobus suberectus and explore the genetic diversity of S. suberectus. A total of 292 ITS2s from S. suberectus and 17 other plant species were analysed. S. suberectus was clustered separately in the phylogenetic tree. The genetic distance between species was greater than that within S. suberectus. Synonymous substitution rate (Ks) analysis revealed that ITS2 diverged the most recently within S. suberectus (Ks = 0.0022). These findings suggested that ITS2 is suitable for the identification of S. suberectus. The ITS2s were divided into 8 haplotypes and 4 evolutionary branches on the basis of secondary structure, indicating that there was variation within S. suberectus. Evolutionary analysis revealed that the GC content of paired regions (pGC) was greater than that of unpaired regions (upGC), and the pGC showed a decreasing trend, whereas the upGC remained unchanged. Single-base mutation was the main cause of base pair substitution. In both the initial state and the equilibrium state, the substitution rate of GC was higher than that of AU. The increase in the GC content was partly attributed to GC-biased gene conversion (gBGC). High GC content reflected the high recombination and mutation rates of ITS2, which is the basis for species identification and genetic diversity. We characterized the sequence and structural characteristics of S. suberectus ITS2 in detail, providing a reference and basis for the identification of S. suberectus and its products, as well as the protection and utilization of wild resources.


Subject(s)
Genetic Variation , Phylogeny , Base Composition , DNA, Ribosomal Spacer/genetics , Evolution, Molecular , Haplotypes , Fabaceae/genetics
2.
Carbohydr Polym ; 344: 122527, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39218534

ABSTRACT

The root of Millettia pulchra (YLS) has been traditionally used as a folk medicine for the treatment of depression and insomnia in the Zhuang nationality of China, and its polysaccharides have potential antidepressant effect. In this study, a novel homogeneous polysaccharide (YLP-1) was purified from the crude polysaccharides of YLS, and it is mainly composed of glucose, arabinose and mannose with molar ratio of 87.25%, 10.77%, and 1.98%, respectively. YLP-1 is a novel α-glucan with the backbone of 1,4-Glcp and branched at C6 of 1,4,6-Glcp to combine 1,4-Manp and 1,5-Araf. The microstructure of YLP-1 displayed a uniform ellipsoidal-like chain morphology and dispersed uniformly in solution. YLP-1 effectively ameliorated depression-like ethological behaviors and restored the decreased catecholamine levels in chronic variable stress (CVS)-induced depression rats. Additionally, it significantly improved the disturbance of gut microbiota induced by CVS stimuli, particularly affecting bacteria that produce short-chain fatty acids (SCFAs), such as bacteria species Lactobacillus spp.. In vitro fermentation study further confirmed that YLP-1 intake could promote SCFAs production by Lactobacillus spp. YLP-1 also mitigated the disruption of tryptophan metabolites in urine and serum. These findings provide evidences for the further development of YLP-1 as a macromolecular antidepressant drug.


Subject(s)
Antidepressive Agents , Fatty Acids, Volatile , Gastrointestinal Microbiome , Millettia , Polysaccharides , Tryptophan , Animals , Gastrointestinal Microbiome/drug effects , Antidepressive Agents/pharmacology , Antidepressive Agents/chemistry , Male , Rats , Polysaccharides/pharmacology , Polysaccharides/chemistry , Millettia/chemistry , Tryptophan/metabolism , Fatty Acids, Volatile/metabolism , Depression/drug therapy , Depression/metabolism , Rats, Sprague-Dawley
3.
Environ Pollut ; 362: 124726, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39173868

ABSTRACT

Although greenspace exposure has physiological health benefits, there is insufficient research on the threshold effect of health benefits in typical urban landscapes. Here we selected five typical urban landscapes (open greenspace, semi-closed greenspace, closed greenspace, bluespace, grey space) in 15 urban parks in Xiamen, China, and applied the physiological health threshold model to calculate the efficiency threshold and benefit threshold of greenspace exposure by continuously monitoring the changes of two physiological indicators-electroencephalography (EEG) and heart rate (HR). (1) The EEG threshold results show that compared with greenspace exposure, bluespace exposure can reach the physiological health efficiency threshold faster (4-5 min) but does not show an advantage in terms of benefit threshold. The more open the greenspace, the faster it can reach the efficiency threshold (5-6 min), but the higher the canopy density of the (closed) greenspace, the shorter the time to reach the efficiency threshold (8-9 min). (2) The HR threshold shows that bluespace and open greenspace are the fastest to reach the efficiency threshold (1 min), with the remaining greenspace reaching it after 6-7 min. The benefit threshold was reached faster in the bluespace (11 min) than in the greenspace (18-21 min), and the degree of openness of the greenspace has no significant effect on the speed of benefit thresholds. (3) Combining the results of EEG and HR thresholds, it can be seen that bluespace is better at reducing stress, while open greenspace can reach efficiency thresholds more quickly. This study confirms the physiological health threshold model, offering a reference for urban greenspace planning to enhance residents' stress management and health.

4.
Plant Physiol Biochem ; 215: 109010, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39146910

ABSTRACT

Soybean is one of the most important crops for producing high quality oil and protein. Mineral nutrient deficiencies are frequently observed in soybeans. However, there are few studies to understand the absorption process of mineral nutrients in soybeans. Here, we investigated the functions of soybean (Glycine max L.) IRT1.1 (IRON-REGULATED TRANSPORTER 1.1) in the transportation of mineral elements. Heterologous expression of GmIRT1.1 in yeast mutants revealed that GmIRT1.1 compensated for the growth defects of Δfet3fet4 and Δsmf1 mutants under iron (Fe) and manganese (Mn) deficiency conditions, respectively, and enhanced the sensitivity of the Δycf1 mutant to cadmium (Cd) toxicity. Expression analysis revealed that GmIRT1.1 was only significantly induced by Fe deficiency and was primarily expressed in roots. Furthermore, the GmIRT1.1 overexpression lines enhanced Arabidopsis tolerance to Fe deficiency, leading to increased accumulation of Fe in the roots and shoots. Additionally, the transgenic lines increased the sensitivity to Mn and Cd toxicity. Subcellular localization analysis revealed that GmIRT1.1 was localized on the plasma membrane. Moreover, the results obtained from the soybean hairy roots system indicated that the localization of GmIRT1.1 was dependent on the regulation of Fe homeostasis in plant. Consequently, these results suggested that GmIRT1.1 was responsible for the transportation of Fe, Mn and Cd.


Subject(s)
Arabidopsis , Cadmium , Glycine max , Iron , Manganese , Plant Proteins , Plants, Genetically Modified , Glycine max/genetics , Glycine max/metabolism , Manganese/metabolism , Iron/metabolism , Cadmium/metabolism , Cadmium/toxicity , Plant Proteins/genetics , Plant Proteins/metabolism , Arabidopsis/genetics , Arabidopsis/metabolism , Biological Transport , Gene Expression Regulation, Plant , Plant Roots/metabolism , Plant Roots/genetics , Cation Transport Proteins/metabolism , Cation Transport Proteins/genetics , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae/genetics
5.
Chemosphere ; 363: 142954, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39069103

ABSTRACT

The organic loading rate (OLR) is a critical parameter affecting the stability of dry anaerobic digestion (AD) of kitchen waste (KW), and significantly impacting the variations in physicochemical parameters and microbial communities. However, the evolution of quorum sensing (QS) and their role on anaerobic biochemical metabolism during the increase in OLR in dry AD remain unknown. Therefore, this study systematically elucidated the matter through multi-omics analysis based on a pilot-scale dry AD of KW. The results demonstrated that fluctuations in the OLR significantly influenced the microbial QS in dry AD. When the OLR ≤4.0 g·VS/L·d, the system operated stably, and methane production increased. The enrichment of Proteobacteria was crucial for sustaining high levels of functional genes associated with various types of QS, including acyl-homoserine lactones (AI-1), autoinducer-2 (AI-2), autoinducer-3 (AI-3), and gamma-aminobutyric acid (GABA). This enabled cooperative communication among microbes under low OLR. Furthermore, most genes associated with these QS processes positively affected hydrolysis, acidogenesis, and methanogenesis. When the OLR increased to 6.0 g·VS/L·d, the fatty acids and hydrogen partial pressure increased significantly. The autoinducing peptides (AIP)-type became the predominant QS and was positively correlated with fatty acids abundance. Syntrophaceticus and Syntrophomonas may promote syntrophic oxidation of acetate at high OLR through AIP-type QS. These findings provided new insights into the QS processes of microbes during dry AD of KW and a theoretical foundation for optimizing biochemical metabolic processes in dry AD through QS.


Subject(s)
Quorum Sensing , Anaerobiosis , Bioreactors/microbiology , Methane/metabolism , Proteobacteria/metabolism , Proteobacteria/genetics
6.
Acta Pharm Sin B ; 14(6): 2657-2668, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38828137

ABSTRACT

A pair of coumarin-based polycyclic meroterpenoid enantiomers (+)/(-)-gerbeloid A [(+)-1a and (-)-1b] were isolated from the medicinal plant Gerbera piloselloides, which have a unique caged oxatricyclo [4.2.2.03,8] decene scaffold. Their planar and three-dimensional structures were exhaustively characterized by comprehensive spectroscopic data and X-ray diffraction analysis. Guided by the hypothetical biosynthetic pathway, the biomimetic synthesis of racemic 1 was achieved using 4-hydroxy-5-methylcoumarin and citral as the starting material via oxa-6π electrocyclization and intramolecular [2 + 2] photocycloaddition. Subsequently, the results of the biological activity assay demonstrated that both (+)-1a and (-)-1b exhibited potent lipid-lowering effects in 3T3-L1 adipocytes and the high-fat diet zebrafish model. Notably, the lipid-lowering activity of (+)-1a is better than that of (-)-1b at the same concentration, and molecular mechanism study has shown that (+)-1a and (-)-1b impairs adipocyte differentiation and stimulate lipolysis by regulating C/EBPα/PPARγ signaling and Perilipin signaling in vitro and in vivo. Our findings provide a promising drug model molecule for the treatment of obesity.

7.
Phys Rev Lett ; 132(16): 160201, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38701466

ABSTRACT

Quantum theory allows information to flow through a single device in a coherent superposition of two opposite directions, resulting into situations where the input-output direction is indefinite. Here we introduce a theoretical method to witness input-output indefiniteness in a single quantum device, and we experimentally demonstrate it by constructing a photonic setup that exhibits input-output indefiniteness with a statistical significance exceeding 69 standard deviations. Our results provide a way to characterize input-output indefiniteness as a resource for quantum information and photonic quantum technologies and enable tabletop simulations of hypothetical scenarios exhibiting quantum indefiniteness in the direction of time.

8.
Neurol Genet ; 10(3): e200159, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38817245

ABSTRACT

Background and Objectives: Multiple sclerosis (MS) age at onset (AAO) is a clinical predictor of long-term disease outcomes, independent of disease duration. Little is known about the genetic and biological mechanisms underlying age of first symptoms. We conducted a genome-wide association study (GWAS) to investigate associations between individual genetic variation and the MS AAO phenotype. Methods: The study population was comprised participants with MS in 6 clinical trials: ADVANCE (N = 655; relapsing-remitting [RR] MS), ASCEND (N = 555; secondary-progressive [SP] MS), DECIDE (N = 1,017; RRMS), OPERA1 (N = 581; RRMS), OPERA2 (N = 577; RRMS), and ORATORIO (N = 529; primary-progressive [PP] MS). Altogether, 3,905 persons with MS of European ancestry were analyzed. GWAS were conducted for MS AAO in each trial using linear additive models controlling for sex and 10 principal components. Resultant summary statistics across the 6 trials were then meta-analyzed, for a total of 8.3 × 10-6 single nucleotide polymorphisms (SNPs) across all trials after quality control and filtering for heterogeneity. Gene-based tests of associations, pathway enrichment analyses, and Mendelian randomization analyses for select exposures were also performed. Results: Four lead SNPs within 2 loci were identified (p < 5 × 10-8), including a) 3 SNPs in the major histocompatibility complex and their effects were independent of HLA-DRB1*15:01 and b) a LOC105375167 variant on chromosome 7. At the gene level, the top association was HLA-C (p = 1.2 × 10-7), which plays an important role in antiviral immunity. Functional annotation revealed the enrichment of pathways related to T-cell receptor signaling, autoimmunity, and the complement cascade. Mendelian randomization analyses suggested a link between both earlier age at puberty and shorter telomere length and earlier AAO, while there was no evidence for a role for either body mass index or vitamin D levels. Discussion: Two genetic loci associated with MS AAO were identified, and functional annotation demonstrated an enrichment of genes involved in adaptive and complement immunity. There was also evidence supporting a link with age at puberty and telomere length. The findings suggest that AAO in MS is multifactorial, and the factors driving onset of symptoms overlap with those influencing MS risk.

9.
Plant Mol Biol ; 114(2): 20, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38363403

ABSTRACT

SQUAMOSA PROMOTER BINDING PROTEIN-LIKEs (SPLs) encode plant-specific transcription factors that regulate plant growth and development, stress response, and metabolite accumulation. However, there is limited information on Scutellaria baicalensis SPLs. In this study, 14 SbSPLs were identified and divided into 8 groups based on phylogenetic relationships. SbSPLs in the same group had similar structures. Abscisic acid-responsive (ABRE) and MYB binding site (MBS) cis-acting elements were found in the promoters of 8 and 6 SbSPLs. Segmental duplications and transposable duplications were the main causes of SbSPL expansion. Expression analysis based on transcriptional profiling showed that SbSPL1, SbSPL10, and SbSPL13 were highly expressed in roots, stems, and flowers, respectively. Expression analysis based on quantitative real-time polymerase chain reaction (RT‒qPCR) showed that most SbSPLs responded to low temperature, drought, abscisic acid (ABA) and salicylic acid (SA), among which the expression levels of SbSPL7/9/10/12 were significantly upregulated in response to abiotic stress. These results indicate that SbSPLs are involved in the growth, development and stress response of S. baicalensis. In addition, 8 Sba-miR156/157 s were identified, and SbSPL1-5 was a potential target of Sba-miR156/157 s. The results of target gene prediction and coexpression analysis together indicated that SbSPLs may be involved in the regulation of L-phenylalanine (L-Phe), lignin and jasmonic acid (JA) biosynthesis. In summary, the identification and characterization of the SbSPL gene family lays the foundation for functional research and provides a reference for improved breeding of S. baicalensis stress resistance and quality traits.


Subject(s)
Abscisic Acid , Scutellaria baicalensis , Abscisic Acid/pharmacology , Abscisic Acid/metabolism , Scutellaria baicalensis/genetics , Scutellaria baicalensis/metabolism , Phylogeny , Plant Breeding , Stress, Physiological/genetics , Hormones/metabolism , Gene Expression Regulation, Plant , Plant Proteins/metabolism
10.
Ann Surg Oncol ; 31(5): 3212-3221, 2024 May.
Article in English | MEDLINE | ID: mdl-38349564

ABSTRACT

BACKGROUND: Traditionally, surgical treatment is recommended for right-sided colonic cancer obstruction (RCCO); however, the literature comparing surgical or non-surgical procedures is lacking. METHODS: Patients included in this study were divided into two groups: one group received elective surgery after self-expanding metal stent (SEMS) placement, i.e., the bridge to surgery (BTS) group, and one group received emergency surgery (ES). RESULTS: Thirty-five patients were included in the BTS group and 60 patients underwent ES. The technical and clinical success rates for SEMS placement were 100% and 88.6%, respectively, while the short-term complication rates were 51.4% and 33.3% for the BTS and ES groups, respectively (p = 0.082). Overall, 2.9% and 3.3% of postoperative deaths occurred in the BTS and ES groups (p = 1.000). The 1-year overall survival (OS) rates were 91.4% and 88.3% (p = 0.840), 3-year OS rates were 85.7% and 81.7% (p = 0.860), and 5-year OS rates were 82.9% and 76.7% (p = 0.620) in the BTS and ES groups, respectively. No tumor recurrence was found in the BTS group but seven recurrences were found in the ES group (11.7%) [p = 0.091]. Laparoscopic surgery was chosen by 42.9% of patients in the BTS group and 26.7% of patients in the ES group (p = 0.104); however, the length of hospital stay (p = 0.001) was longer in the BTS group. CONCLUSIONS: In the two groups, no differences were found in terms of postoperative complications and mortality as well as OS. The BTS group preferred to perform laparoscopic surgery and the technical success rate of stenting was high, therefore SEMS for RCCO was considered safe and feasible.


Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Intestinal Obstruction , Self Expandable Metallic Stents , Humans , Colorectal Neoplasms/pathology , Self Expandable Metallic Stents/adverse effects , Neoplasm Recurrence, Local/complications , Colonic Neoplasms/complications , Colonic Neoplasms/surgery , Stents/adverse effects , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Treatment Outcome , Retrospective Studies
12.
Front Public Health ; 12: 1309632, 2024.
Article in English | MEDLINE | ID: mdl-38414898

ABSTRACT

Background: For high-quality colonoscopies, adequate bowel preparation is a prerequisite, closely associated with the diagnostic accuracy and therapeutic safety of colonoscopy. Although popular-science short videos can help people quickly access health information, the overall quality of such short videos as a source of health information regarding bowel preparation before colonoscopy is unclear. Therefore, we intend to conduct a cross-sectional study to investigate the quality of bowel preparation information before colonoscopy through short videos taken on TikTok and Bilibili. Methods: The Chinese phrases "colonoscopy" and "bowel preparation" were used as keywords to search for and screen the top 100 videos in the comprehensive rankings on TikTok and Bilibili. The Global Quality Score (GQS) and the modified DISCERN score were used to assess the quality of the information provided in these short videos. Results: A total of 186 short videos were included in this study; 56.5% of them were posted by health professionals, whereas 43.5% of them were posted by nonhealth professionals. The overall quality of these videos was unsatisfactory, with a median DISCERN score of 3 (2-4) and a median GQS of 3 (3-4). The radar maps showed that videos posted by gastroenterologists had higher completeness scores regarding outcomes, management, and risk factors, while nongastroenterologists had higher completeness scores concerning adverse effects, symptoms, and definitions of bowel preparation. Additionally, the median DISCERN score and GQS of the videos posted by gastroenterologists were 3 (3-4) and 3 (3-4), respectively, whereas the quality of the videos posted by patients was the worst, with a median DISCERN score of 2 (1-2) and a median GQS of 2 (1.25-3). Conclusion: In conclusion, the overall quality of health information-related videos on bowel preparation before colonoscopy posted on specified short video platforms was not satisfactory. Gastroenterologists provide more information on the outcomes, management, and risk factors for bowel preparation before colonoscopy, while nongastroenterologists focus on adverse effects, symptoms, and definitions of bowel preparation.


Subject(s)
Colonoscopy , Patient Education as Topic , Humans , Cross-Sectional Studies , Risk Factors , Audiovisual Aids
13.
Opt Express ; 32(3): 2906-2915, 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38297527

ABSTRACT

We present a novel micro-fabrication technique for creating concave surfaces on the endfacets of photonic crystal fibers. A fiber fusion splicer is used to generate arc discharges to melt and reshape the fiber endfacet. This technique can produce large spherical concave surfaces with roughness as low as 0.12 nm in various types of photonic crystal fibers. The deviation of fabricated surface and a spherical profile in the region of 70 µm in diameter is less than 50 nm. The center of the concave surface and the fiber mode field are highly coincident with a deviation less than 500 nm. Finesse measurements have shown that a Fabry-Pérot cavity composed of the fiber fabricated using this method and a plane mirror maintains finesse of 20000. This method is easy to replicate, making it a practical and efficient approach to fabricate concave surface on fibers for open-access fiber Fabry-Pérot cavities.

14.
PhytoKeys ; 237: 79-89, 2024.
Article in English | MEDLINE | ID: mdl-38282985

ABSTRACT

Aletrisguangxiensis Y. Nong & Y. F. Huang (Nartheciaceae), a new species from Guangxi, China, is described and illustrated. This new species is most similar to A.scopulorum, but it can be easily distinguished by its sparsely glandular, 5-18 cm long scape, glandular inflorescence axis, distinctly pedicellate flowers, sparsely glandular, 5-10 mm long pedicel, bract borne at base of pedicel, glabrous perianth divided to the base, strongly recurved or revolute perianth lobes and turbinate, obovoid to oblong-obovoid capsule. An identification key for 24 species and 1 hybrid of Aletris is also provided.

15.
BMC Endocr Disord ; 23(1): 272, 2023 Dec 07.
Article in English | MEDLINE | ID: mdl-38057786

ABSTRACT

OBJECTIVES: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by chronic hyperglycemia and metabolic stress, involved in the stepwise development of cardiovascular complications. Fibroblast growth factor 21 (FGF21) is a novel hepatokine involved in regulating glucose and lipid metabolism, and has been linked to the prediction, treatment, and improvement of prognosis in multiple cardiovascular diseases (CVDs). The aim of this study is to explore the relationship between FGF21 levels and vascular diseases (VDs) including carotid atherosclerosis (CAS) and hypertension (HP) in patients with T2DM. METHODS: Baseline serum FGF21 was determined in a cross-sectional study of 701 patients with T2DM and 258 healthy control. RESULTS: The morbidity of CAS was increased in T2DM patients with HP as compared with those without (p < 0.001). The average serum FGF21 level of healthy was [123.9 (67.2-219.3)]. Baseline FGF21 was significantly higher in those who developed CAS or HP than in those who did not [305.9 (177.2-508.4) vs. 197.2 (129.7-308.3) pg/mL, p < 0.001]. In addition, an elevated serum FGF21 was observed in T2DM patients with HP and CAS than that of T2DM patients with CAS or HP [550.5 (312.6-711.3) vs. 305.9 pg/mL, p < 0.001]. Serum FGF21 levels were positively correlated with body mass index and carotid intima media thicknes (p < 0.05), the association remained significant after adjusting for age and T2DM duration. Furthermore, the multinomial logistic regression showed that serum FGF21 was independently associated with CAS and HP in patients with T2DM after adjustment for demographic and traditional VDs risk factors (p < 0.001). CONCLUSIONS: Baseline FGF21 is elevated in VDs during diabetes, changes of serum FGF21 levels were appropriately matched to metabolic stress. FGF21can be used as an independent predictor for diagnosing VDs and predicting prognosis.


Subject(s)
Carotid Artery Diseases , Diabetes Mellitus, Type 2 , Adult , Child, Preschool , Humans , Cross-Sectional Studies , Fibroblast Growth Factors
16.
PhytoKeys ; 234: 219-227, 2023.
Article in English | MEDLINE | ID: mdl-37927972

ABSTRACT

Walsuraguangxiensis (Meliaceae), a new species from Guangxi, China, is here described and illustrated. The new species is easily distinguishable from the other two Chinese members of the genus by its petals being pale yellow, filaments being connate into tubes above the middle, the berry being oval and glabrous. An identification key of Walsura for 17 species is also provided.

17.
Sci Rep ; 13(1): 14313, 2023 08 31.
Article in English | MEDLINE | ID: mdl-37652990

ABSTRACT

While the genetics of MS risk susceptibility are well-described, and recent progress has been made on the genetics of disease severity, the genetics of disease progression remain elusive. We therefore investigated the genetic determinants of MS progression on longitudinal brain MRI: change in brain volume (BV) and change in T2 lesion volume (T2LV), reflecting progressive tissue loss and increasing disease burden, respectively. We performed genome-wide association studies of change in BV (N = 3401) and change in T2LV (N = 3513) across six randomized clinical trials from Biogen and Roche/Genentech: ADVANCE, ASCEND, DECIDE, OPERA I & II, and ORATORIO. Analyses were adjusted for randomized treatment arm, age, sex, and ancestry. Results were pooled in a meta-analysis, and were evaluated for enrichment of MS risk variants. Variant colocalization and cell-specific expression analyses were performed using published cohorts. The strongest peaks were in PTPRD (rs77321193-C/A, p = 3.9 × 10-7) for BV change, and NEDD4L (rs11398377-GC/G, p = 9.3 × 10-8) for T2LV change. Evidence of colocalization was observed for NEDD4L, and both genes showed increased expression in neuronal and/or glial populations. No association between MS risk variants and MRI outcomes was observed. In this unique, precompetitive industry partnership, we report putative regions of interest in the neurodevelopmental gene PTPRD, and the ubiquitin ligase gene NEDD4L. These findings are distinct from known MS risk genetics, indicating an added role for genetic progression analyses and informing drug discovery.


Subject(s)
Brain , Genome-Wide Association Study , Multiple Sclerosis , Humans , Brain/diagnostic imaging , Cost of Illness , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/genetics , Neuroimaging , Randomized Controlled Trials as Topic , Disease Progression
18.
Nat Commun ; 14(1): 3449, 2023 06 10.
Article in English | MEDLINE | ID: mdl-37301943

ABSTRACT

Muscle strength is highly heritable and predictive for multiple adverse health outcomes including mortality. Here, we present a rare protein-coding variant association study in 340,319 individuals for hand grip strength, a proxy measure of muscle strength. We show that the exome-wide burden of rare protein-truncating and damaging missense variants is associated with a reduction in hand grip strength. We identify six significant hand grip strength genes, KDM5B, OBSCN, GIGYF1, TTN, RB1CC1, and EIF3J. In the example of the titin (TTN) locus we demonstrate a convergence of rare with common variant association signals and uncover genetic relationships between reduced hand grip strength and disease. Finally, we identify shared mechanisms between brain and muscle function and uncover additive effects between rare and common genetic variation on muscle strength.


Subject(s)
Hand Strength , Muscular Diseases , Humans , Muscle Strength/genetics , Mutation, Missense , Genetic Predisposition to Disease , Carrier Proteins
19.
Phys Rev Lett ; 130(15): 150801, 2023 Apr 14.
Article in English | MEDLINE | ID: mdl-37115884

ABSTRACT

Recently, a proper genuine multipartite entanglement measure has been found for three-qubit pure states [see Xie and Eberly, Phys. Rev. Lett. 127, 040403 (2021)PRLTAO0031-900710.1103/PhysRevLett.127.040403], but capturing useful entanglement measures for mixed states has remained an open challenge. So far, it requires not only a full tomography in experiments, but also huge calculational labor. A leading proposal was made by Gühne, Reimpell, and Werner [Phys. Rev. Lett. 98, 110502 (2007)PRLTAO0031-900710.1103/PhysRevLett.98.110502], who used expectation values of entanglement witnesses to describe a lower bound estimation of entanglement. We provide here an extension that also gives genuine upper bounds of entanglement. This advance requires only the expectation value of any Hermitian operator. Moreover, we identify a class of operators A_{1} that not only give good estimates, but also require a remarkably small number of experimental measurements. In this Letter, we define our approach and illustrate it by estimating entanglement measures for a number of pure and mixed states prepared in our recent experiments.

20.
Nat Commun ; 14(1): 2153, 2023 Apr 14.
Article in English | MEDLINE | ID: mdl-37059704

ABSTRACT

Networks composed of independent sources of entangled particles that connect distant users are a rapidly developing quantum technology and an increasingly promising test-bed for fundamental physics. Here we address the certification of their post-classical properties through demonstrations of full network nonlocality. Full network nonlocality goes beyond standard nonlocality in networks by falsifying any model in which at least one source is classical, even if all the other sources are limited only by the no-signaling principle. We report on the observation of full network nonlocality in a star-shaped network featuring three independent sources of photonic qubits and joint three-qubit entanglement-swapping measurements. Our results demonstrate that experimental observation of full network nonlocality beyond the bilocal scenario is possible with current technology.

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