| 1. |
- Kumar, Atul, et al.
(författare)
-
The structure of Rv3717 reveals a novel amidase from Mycobacterium tuberculosis.
- 2013
-
Ingår i: Acta Crystallographica Section D. - : Wiley-Blackwell. - 0907-4449 .- 1399-0047. ; 69:Pt 12, s. 2543-54
-
Tidskriftsartikel (refereegranskat)abstract
- Bacterial N-acetylmuramoyl-L-alanine amidases are cell-wall hydrolases that hydrolyze the bond between N-acetylmuramic acid and L-alanine in cell-wall glycopeptides. Rv3717 of Mycobacterium tuberculosis has been identified as a unique autolysin that lacks a cell-wall-binding domain (CBD) and its structure has been determined to 1.7 Å resolution by the Pt-SAD phasing method. Rv3717 possesses an α/β-fold and is a zinc-dependent hydrolase. The structure reveals a short flexible hairpin turn that partially occludes the active site and may be involved in autoregulation. This type of autoregulation of activity of PG hydrolases has been observed in Bartonella henselae amidase (AmiB) and may be a general mechanism used by some of the redundant amidases to regulate cell-wall hydrolase activity in bacteria. Rv3717 utilizes its net positive charge for substrate binding and exhibits activity towards a broad spectrum of substrate cell walls. The enzymatic activity of Rv3717 was confirmed by isolation and identification of its enzymatic products by LC/MS. These studies indicate that Rv3717, an N-acetylmuramoyl-L-alanine amidase from M. tuberculosis, represents a new family of lytic amidases that do not have a separate CBD and are regulated conformationally.
|
|
| 2. |
- Thakur, Hemant, et al.
(författare)
-
Anaerobic co-digestion of food waste, bio-flocculated sewage sludge, and cow dung in CSTR using E(C2)Tx synthetic consortia
- 2023
-
Ingår i: Environmental Technology & Innovation. - 2352-1864. ; 32
-
Tidskriftsartikel (refereegranskat)abstract
- In the current study, a E(C2)Tx synthetic consortia was tested for anaerobic co-digestion of food waste (FW), bio-flocculated sewage sludge (BFS)/ raw wastewater (RW) and cow dung (CD) at varying proportions in 0.25 L and 6.5 L mesophilic continuously stirred tank reactors. Anaerobic co-digestion of FW with CD and RW at the ratio of 1:1:8 in 0.25 L batch-reactor with E(C2)Tx inoculum resulted in the highest H2 production with least CO2 release. The microbial dynamics of FW:CD:RW samples were studied using 16S metagenomic sequencing which indicated a predominance of hydrolysing microbes at the end point of the digestion cycle. Subsequently, the experiments were scaled up in two continuous digesters, namely, R1 (fed with 50% FW and 50% BFS) and R2 (fed with 2% FW and 98% BFS) with 6.5 L working volume at 2.5 g VS L-1D-1 organic loading rate (OLR) for 120 days. The highest VFA production of 19,183 mg L-1 and 3,265 mg L-1 with maximum bio-methane yield of 142.21-and 225.03-mL CH4g-1 VSadded were recorded in reactors R1 and R2, respectively. In addition, a numerical analysis was conducted to visualize the mixing and temperature distribution within the digesters, and the velocity and temperature profiles were obtained using Ansys Fluent. & COPY; 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
|
|
| 3. |
- Bentham, James, et al.
(författare)
-
A century of trends in adult human height
- 2016
-
Ingår i: eLIFE. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
|
|
| 4. |
- Bentham, James, et al.
(författare)
-
A century of trends in adult human height
- 2016
-
Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Kumar, Manish, et al.
(författare)
-
Global co-occurrences of multi-(emerging)-contaminants in the hotspots of arsenic polluted groundwater : A pattern of menace
- 2023
-
Ingår i: Current Opinion in Environmental Science & Health. - : Elsevier BV. - 2468-5844. ; 34
-
Forskningsöversikt (refereegranskat)abstract
- Advancements in analytical techniques have resulted in much progress in understanding co-occurrence of environmental con-taminants. We focused on investigating the global pattern of arsenic (As) co-occurrence with inorganic and emerging con-taminants and then explained the governing factors driving the situation. Major co-occurring inorganic contaminants were found in three sets: i) U, F, Fe, Mn, Pb, & Zn; ii) Al, Mo, Cd, Sb, Br, I, and Se; and iii) Ag, Au, Cr, Cu, Hg, Th, V, Ga, and Ba. Co-occurrences were majorly governed by weathering, redox conditions, recharge/pumping, and surface leaching. Several places around the world started to exhibit As presence with contaminants of emerging concerns like pesticides, per-and polyfluoroalkyl sub-stances (PFAS), endocrine disrupting chemicals (EDCs), and others, that needs to be explored further at fundamentally deeper levels. This is probably one of the first attempts to correlate As co -occurrences with contaminants of emerging concern.
|
|
| 8. |
- Mishra, Abhay, et al.
(författare)
-
Spectroscopic insight into breast cancer: profiling small extracellular vesicles lipids via infrared spectroscopy for diagnostic precision
- 2024
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- Breast cancer, a leading cause of female mortality due to delayed detection owing to asymptomatic nature and limited early diagnostic tools, was investigated using a multi-modal approach. Plasma-derived small EVs from breast cancer patients (BrCa, n = 74) and healthy controls (HC, n = 30) were analyzed. Small EVs (n = 104), isolated through chemical precipitation, underwent characterization via transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Validation involved antibody-based tests (TSG101, CD9, CD81, CD63). Infrared spectra of small EVs were obtained, revealing significant differences in lipid acyl chains, particularly in the C–H stretching of CH3. The study focused on the lipid region (3050–2900 cm−1), identifying peaks (3015 cm−1, 2960 cm−1, 2929 cm−1) as distinctive lipid characteristics. Spectroscopic lipid-to-lipid ratios [(I3015/I2929), (I2960/I2929)] emerged as prominent breast cancer markers. Exploration of protein, nucleic acid, and carbohydrate ratios indicated variations in alpha helices, asymmetric C–H stretching vibrations, and C–O stretching at 1033 cm−1. Principal component analysis (PCA) successfully differentiated BrCa and HC small EVs, and heatmap analysis and receiver operating characteristic (ROC) curve evaluations underscored the discriminatory power of lipid ratios. Notably, (I2960/I2929) exhibited 100% sensitivity and specificity, highlighting its potential as a robust BrCa sEV marker for breast cancer detection.
|
|
| 9. |
- Misra, Satabdi, et al.
(författare)
-
Multi-proxy approach on the hydrocarbon generation perspective of Barjora Basin, India
- 2020
-
Ingår i: Marine and Petroleum Geology. - : Elsevier. - 0264-8172 .- 1873-4073. ; 112
-
Tidskriftsartikel (refereegranskat)abstract
- Barjora Basin in India is a small basin characterized by a high organic richness of early mature nature. The present study aims to find the source of organic matter (OM) and hydrocarbon generation potential of Barjora Basin. Systematically collected coal and shale samples from R-II seam of the basin were used for proximate and ultimate analyses, Rock Eval pyrolysis along with total organic carbon (TOC) content, organo-micropetrographic framework, thermal maturity, carbon isotopic signature, biomarker composition, functional group studies and estimation of relative aliphaticity and aromaticity through Fourier Transform infrared spectroscopy (FTIR). The novelty of the present work lies in the application of multiple proxies such as stable isotope ratio of organic carbon (delta C-13), biomarker signatures, thermal maturity parameters, organo-micropetrography and estimation and quantification of functional groups for palaeoenvironmental reconstruction and to assess the hydrocarbon productivity of the basin. A dominant terrestrial OM input in Barjora Basin is indicated by the TOC to total nitrogen ratio (C/N), delta C-13 and biomarker compositions. High gelification index (GI), tissue preservation index (TPI), and carbon preference index (CPI) values indicate that coals are deposited in wet swamp forest regime under high rainwater conditions and shales are formed in upper delta plain regime under high groundwater activity. In addition, large liptinite content, TPI and GI designate short transportation of the OM before burial leading to organic richness of the Barjora Basin. Moreover, high liptinite content, type II-III admixed kerogen input, S-2/S-3 ratio, TPI and index for hydrocarbon generation (I-HG) signify higher potential of the basin for hydrocarbon generation.
|
|
| 10. |
- Bonnardel, Francois, et al.
(författare)
-
Architecture and Evolution of Blade Assembly in beta-propeller Lectins
- 2019
-
Ingår i: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 27:5, s. 764-
-
Tidskriftsartikel (refereegranskat)abstract
- Lectins with a beta-propeller fold bind glycans on the cell surface through multivalent binding sites and appropriate directionality. These proteins are formed by repeats of short domains, raising questions about evolutionary duplication. However, these repeats are difficult to detect in translated genomes and seldom correctly annotated in sequence databases. To address these issues, we defined the blade signature of the five types of beta-propellers using 3D-structural data. With these templates, we predicted 3,887 beta-propeller lectins in 1,889 species and organized this information in a searchable online database. The data reveal a widespread distribution of beta-propeller lectins across species. Prediction also emphasizes multiple architectures and led to the discovery of a beta-propeller assembly scenario. This was confirmed by producing and characterizing a predicted protein coded in the genome of Kordia zhangzhouensis. The crystal structure uncovers an intermediate in the evolution of beta-propeller assembly and demonstrates the power of our tools.
|
|
| 11. |
- Cavalli, Marco, et al.
(författare)
-
Single Nuclei Transcriptome Analysis of Human Liver with Integration of Proteomics and Capture Hi-C Bulk Tissue Data
-
Tidskriftsartikel (refereegranskat)abstract
- The liver is the largest solid organ and a primary metabolic hub. In recent years, intact cell nuclei were used to perform single-nuclei RNA-seq (snRNA-seq) for tissues difficult to dissociate and for flash-frozen archived tissue samples to discover unknown and rare cell sub-populations. In this study, we performed snRNA-seq of a liver sample to identify sub-populations of cells based on nuclear transcriptomics. In 4,282 single nuclei we detected on average 1,377 active genes and we identified seven major cell types. We integrated data from 94,286 distal interactions (p<0.05) for 7,682 promoters from a targeted chromosome conformation capture technique (HiCap) and mass spectrometry (MS) proteomics for the same liver sample. We observed a reasonable correlation between proteomics and in silico bulk snRNA-seq (r=0.47) using tissue-independent gene-specific protein abundancy estimation factors. We specifically looked at genes of medical importance. The DPYD gene is involved in the pharmacogenetics of fluoropyrimidines toxicity and some of its variants are analyzed for clinical purposes. We identified a new putative polymorphic regulatory element, which may contribute to variation in toxicity. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and we investigated all known risk genes. We found a complex regulatory network for the SLC2A2 gene with 16 candidate enhancers. Three of them harbor somatic motif breaking and other mutations in HCC in the Pan Cancer Analysis of Whole Genomes dataset and are candidates to contribute to malignancy. Our results highlight the potential of a multi-omics approach in the study of human diseases.
|
|
| 12. |
- Dybjer, Elin, et al.
(författare)
-
Polygenic risk of type 2 diabetes is associated with incident vascular dementia : a prospective cohort study
- 2023
-
Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 5:2
-
Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes and dementia are associated, but it is unclear whether the two diseases have common genetic risk markers that could partly explain their association. It is also unclear whether the association between the two diseases is of a causal nature. Furthermore, few studies on diabetes and dementia have validated dementia end-points with high diagnostic precision. We tested associations between polygenic risk scores for type 2 diabetes, fasting glucose, fasting insulin and haemoglobin A1c as exposure variables and dementia as outcome variables in 29 139 adults (mean age 55) followed for 20–23 years. Dementia diagnoses were validated by physicians through data from medical records, neuroimaging and biomarkers in cerebrospinal fluid. The dementia end-points included all-cause dementia, mixed dementia, Alzheimer’s disease and vascular dementia. We also tested causal associations between type 2 diabetes and dementia through two-sample Mendelian randomization analyses. Seven different polygenic risk scores including single-nucleotide polymorphisms with different significance thresholds for type 2 diabetes were tested. A polygenic risk score including 4891 single-nucleotide polymorphisms with a P-value of <5e-04 showed the strongest association with different outcomes, including all-cause dementia (hazard ratio 1.11; Bonferroni corrected P = 3.6e-03), mixed dementia (hazard ratio 1.18; Bonferroni corrected P = 3.3e-04) and vascular dementia cases (hazard ratio 1.28; Bonferroni corrected P = 9.6e-05). The associations were stronger for non-carriers of the Alzheimer’s disease risk gene APOE ϵ4. There was, however, no significant association between polygenic risk scores for type 2 diabetes and Alzheimer’s disease. Furthermore, two-sample Mendelian randomization analyses could not confirm a causal link between genetic risk markers of type 2 diabetes and dementia outcomes. In conclusion, polygenic risk of type 2 diabetes is associated with an increased risk of dementia, in particular vascular dementia. The findings imply that certain people with type 2 diabetes may, due to their genetic background, be more prone to develop diabetes-associated dementia. This knowledge could in the future lead to targeted preventive strategies in clinical practice.
|
|
| 13. |
- Franzmeier, Nicolai, et al.
(författare)
-
The BIN1 rs744373 Alzheimer's disease risk SNP is associated with faster Aβ-associated tau accumulation and cognitive decline
- 2022
-
Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:1, s. 103-115
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The BIN1 rs744373 single nucleotide polymorphism (SNP) is a key genetic risk locus for Alzheimer's disease (AD) associated with tau pathology. Because tau typically accumulates in response to amyloid beta (Aβ), we tested whether BIN1 rs744373 accelerates Aβ-related tau accumulation. Methods: We included two samples (Alzheimer's Disease Neuroimaging Initiative [ADNI], n = 153; Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably [BioFINDER], n = 63) with longitudinal 18F-Flortaucipir positron emission tomography (PET), Aβ biomarkers, and longitudinal cognitive assessments. We assessed whether BIN1 rs744373 was associated with faster tau-PET accumulation at a given level of Aβ and whether faster BIN1 rs744373-associated tau-PET accumulation mediated cognitive decline. Results: BIN1 rs744373 risk-allele carriers showed faster global tau-PET accumulation (ADNI/BioFINDER, P <.001/P <.001). We found significant Aβ by rs744373 interactions on global tau-PET change (ADNI: β/standard error [SE] = 0.42/0.14, P = 0.002; BioFINDER: β/SE = –0.35/0.15, P =.021), BIN1 risk-allele carriers showed accelerated tau-PET accumulation at higher Aβ levels. In ADNI, rs744373 effects on cognitive decline were mediated by faster global tau-PET accumulation (β/SE = 0.20/0.07, P =.005). Discussion: BIN1-associated AD risk is potentially driven by accelerated tau accumulation in the face of Aβ.
|
|
| 14. |
- Hansson, Oskar, et al.
(författare)
-
The genetic regulation of protein expression in cerebrospinal fluid
- 2023
-
Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- Studies of the genetic regulation of cerebrospinal fluid (CSF) proteins may reveal pathways for treatment of neurological diseases. 398 proteins in CSF were measured in 1,591 participants from the BioFINDER study. Protein quantitative trait loci (pQTL) were identified as associations between genetic variants and proteins, with 176 pQTLs for 145 CSF proteins (P < 1.25 × 10−10, 117 cis-pQTLs and 59 trans-pQTLs). Ventricular volume (measured with brain magnetic resonance imaging) was a confounder for several pQTLs. pQTLs for CSF and plasma proteins were overall correlated, but CSF-specific pQTLs were also observed. Mendelian randomization analyses suggested causal roles for several proteins, for example, ApoE, CD33, and GRN in Alzheimer's disease, MMP-10 in preclinical Alzheimer's disease, SIGLEC9 in amyotrophic lateral sclerosis, and CD38, GPNMB, and ADAM15 in Parkinson's disease. CSF levels of GRN, MMP-10, and GPNMB were altered in Alzheimer's disease, preclinical Alzheimer's disease, and Parkinson's disease, respectively. These findings point to pathways to be explored for novel therapies. The novel finding that ventricular volume confounded pQTLs has implications for design of future studies of the genetic regulation of the CSF proteome.
|
|
| 15. |
- Huang, Phillips Y, et al.
(författare)
-
Lgr6 is a stem cell marker in mouse skin squamous cell carcinoma
- 2017
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 49:11, s. 1624-1632
-
Tidskriftsartikel (refereegranskat)abstract
- The G-protein-coupled receptors LGR4, LGR5 and LGR6 are Wnt signaling mediators, but their functions in squamous cell carcinoma (SCC) are unclear. Using lineage tracing in Lgr5-EGFP-CreERT2/Rosa26-Tomato and Lgr6-EGFP-CreERT2/Rosa26-Tomato reporter mice, we demonstrate that Lgr6, but not Lgr5, acts as an epithelial stem cell marker in SCCs in vivo. We identify, by single-molecule in situ hybridization and cell sorting, rare cells positive for Lgr6 expression in immortalized keratinocytes and show that their frequency increases in advanced SCCs. Lgr6 expression is enriched in cells with stem cell characteristics, and Lgr6 downregulation in vivo causes increased epidermal proliferation with expanded lineage tracing from epidermal stem cells positive for Lgr6 expression. Surprisingly, mice with germline knockout of Lgr6 are predisposed to SCC development, through a mechanism that includes compensatory upregulation of Lgr5. These data provide a model for human patients with germline loss-of-function mutations in Wnt pathway genes, including RSPO1 or LGR4, who show increased susceptibility to squamous tumor development.
|
|
| 16. |
- Insel, Philip S., et al.
(författare)
-
Genetic Moderation of the Association of β-Amyloid With Cognition and MRI Brain Structure in Alzheimer Disease
- 2023
-
Ingår i: Neurology. - 0028-3878. ; 101:1, s. 20-29
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: There is considerable heterogeneity in the association between increasing β-amyloid (Aβ) pathology and early cognitive dysfunction in preclinical Alzheimer disease (AD). At this stage, some individuals show no signs of cognitive dysfunction, while others show clear signs of decline. The factors explaining this heterogeneity are particularly important for understanding progression in AD but remain largely unknown. In this study, we examined an array of genetic variants that may influence the relationships among Aβ, brain structure, and cognitive performance in 2 large cohorts. Methods: In 2,953 cognitively unimpaired participants from the Anti-Amyloid Treatment in Asymptomatic Alzheimer disease (A4) study, interactions between genetic variants and 18F-Florbetapir PET standardized uptake value ratio (SUVR) to predict the Preclinical Alzheimer Cognitive Composite (PACC) were assessed. Genetic variants identified in the A4 study were evaluated in the Alzheimer Disease Neuroimaging Initiative (ADNI, N = 527) for their association with longitudinal cognition and brain atrophy in both cognitively unimpaired participants and those with mild cognitive impairment. Results: In the A4 study, 4 genetic variants significantly moderated the association between Aβ load and cognition. Minor alleles of 3 variants were associated with additional decreases in PACC scores with increasing Aβ SUVR (rs78021285, β = -2.29, SE = 0.40, pFDR = 0.02, nearest gene ARPP21; rs71567499, β = -2.16, SE = 0.38, pFDR = 0.02, nearest gene PPARD; and rs10974405, β = -1.68, SE = 0.29, pFDR = 0.02, nearest gene GLIS3). The minor allele of rs7825645 was associated with less decrease in PACC scores with increasing Aβ SUVR (β = 0.71, SE = 0.13, pFDR = 0.04, nearest gene FGF20). The genetic variant rs76366637, in linkage disequilibrium with rs78021285, was available in both the A4 and ADNI. In the A4, rs76366637 was strongly associated with reduced PACC scores with increasing Aβ SUVR (β = -1.01, SE = 0.21, t = -4.90, p < 0.001). In the ADNI, rs76366637 was associated with accelerated cognitive decline (χ2 = 15.3, p = 0.004) and atrophy over time (χ2 = 26.8, p < 0.001), with increasing Aβ SUVR. Discussion: Patterns of increased cognitive dysfunction and accelerated atrophy due to specific genetic variation may explain some of the heterogeneity in cognition in preclinical and prodromal AD. The genetic variant near ARPP21 associated with lower cognitive scores in the A4 and accelerated cognitive decline and brain atrophy in the ADNI may help to identify those at the highest risk of accelerated progression of AD.
|
|
| 17. |
- Johri, Atul K., et al.
(författare)
-
Fungal association and utilization of phosphate by plants : success, limitations, and future prospects
- 2015
-
Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 6
-
Forskningsöversikt (refereegranskat)abstract
- Phosphorus (P) is a major macronutrient for plant health and development. The available form of P is generally low in the rhizosphere even in fertile soils. A major proportion of applied phosphate (Pi) fertilizers in the soil become fixed into insoluble, unavailable forms, which restricts crop production throughout the world. Roots possess two distinct modes of P uptake from the soil, direct and indirect uptake. The direct uptake of P is facilitated by the plant's own Pi transporters while indirect uptake occurs via mycorrhizal symbiosis, where the host plant obtains P primarily from the fungal partner, while the fungus benefits from plant-derived reduced carbon. So far, only one Pi transporter has been characterized from the mycorrhizal fungus Glomus versiforme. As arbuscular mycorrhizal fungi cannot be cultured axenically, their Pi transporter network is difficult to exploite for large scale sustainable agriculture. Alternatively, the root-colonizing endophytic fungus Piriformospora indica can grow axenically and provides strong growth-promoting activity during its symbiosis with a broad spectrum of plants. P indica contains a high affinity Pi transporter (PiPT) involved in improving Pi nutrition levels in the host plant under P limiting conditions. As P indica can be manipulated genetically, it opens new vistas to be used in P deficient fields.
|
|
| 18. |
- Kirillova, Elena N., et al.
(författare)
-
Water-soluble organic carbon aerosols during a full New Delhi winter : Isotope-based source apportionment and optical properties
- 2014
-
Ingår i: JOURNAL OF GEOPHYSICAL RESEARCH - ATMOSPHERES. - 2169-8996. ; 119:6, s. 3476-3485
-
Tidskriftsartikel (refereegranskat)abstract
- Water soluble organic carbon (WSOC) aerosol is a major constituent (~ 20-80% of the total organic carbon) of the ‘brown cloud’ that shades the Indian Subcontinent. Due to the multiple formation pathways (both primary and secondary), the emissions sources of WSOC are particularly poorly constrained. In this study, we present radiocarbon constraints on the biomass vs fossil sources of WSOC in PM2.5 for the 2010/11 winter period for the megacity Delhi, situated in the center of the heavily polluted Indo-Gangetic Plain. The fossil contribution (22±4%) to WSOC in Delhi is found to be similar to fossil fraction at Indian background sites. Stable carbon analysis shows that Delhi WSOC is more depleted in 13C relative to what is found at receptor sites, indicating that near-source WSOC is less affected by atmospheric aging. In addition, the light absorptive properties of WSOC were investigated. The mass absorption cross section at 365 nm (MAC365) ranged 1.1 – 2.7 m2/g, and the corresponding absorption Ångström exponent (AAE) ranged between 3.1 and 9.3. Using a simplistic estimate of the relative absorptive radiative forcing was found to be 6 – 42 % relative to that of black carbon. Taken together this near-source study emphasize the importance of taking into account the complex transformations of WSOC during air mass transport, as compared with regional receptor sites.
|
|
| 19. |
- Kumar, Atul, et al.
(författare)
-
Genetic effects on longitudinal cognitive decline during the early stages of Alzheimer’s disease
- 2021
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Cognitive decline in early-stage Alzheimer’s disease (AD) may depend on genetic variability. In the Swedish BioFINDER study, we used polygenic scores (PGS) (for AD, intelligence, and educational attainment) to predict longitudinal cognitive change (measured by mini-mental state examination (MMSE) [primary outcome] and other cognitive tests) over a mean of 4.2 years. We included 260 β-amyloid (Aβ) negative cognitively unimpaired (CU) individuals, 121 Aβ-positive CU (preclinical AD), 50 Aβ-negative mild cognitive impairment (MCI) patients, and 127 Aβ-positive MCI patients (prodromal AD). Statistical significance was determined at Bonferroni corrected p value < 0.05. The PGS for intelligence (beta = 0.1, p = 2.9e−02) was protective against decline in MMSE in CU and MCI participants regardless of Aβ status. The polygenic risk score for AD (beta = − 0.12, p = 9.4e−03) was correlated with the rate of change in MMSE and was partially mediated by Aβ-pathology (mediation effect 20%). There was no effect of education PGS on cognitive measures. Genetic variants associated with intelligence mitigate cognitive decline independent of Aβ-pathology, while effects of genetic variants associated with AD are partly mediated by Aβ-pathology.
|
|
| 20. |
- Kumar, Atul, et al.
(författare)
-
Genetic influence during the early phases of Alzheimer's disease on longitudinal cognitive impairment
- 2021
-
Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - 1552-5279. ; 17
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The rate of cognitive decline in the early stages of Alzheimer's disease (AD) is variable, which may be partly due to genetic factors. We therefore investigated genetic predictors of longitudinal cognitive decline in AD. METHOD: In the Swedish BioFINDER study, we used polygenic scores (PGS) (of AD, intelligence and educational attainment), and genetic variants (in a genome-wide association study [GWAS]) to predict longitudinal change in cognition (measured by MMSE) over a mean of 4.2 years. We included 555 b-amyloid (Aβ) negative cognitively unimpaired (CU) individuals, 206 Aβ-positive CU (preclinical AD), 110 Aβ-negative mild cognitive impairment (MCI) patients, and 146 Aβ-positive MCI patients (prodromal AD). Mixed-effect models were fitted with longitudinal MMSE data as dependent variable. Random slopes and intercepts were extracted and were rank-based inverse normal transformed (INT) to be used as dependent variables in linear regression models. RESULT: AD polygenic risk score (PRS) and intelligence PGS (but not education PGS) were associated with rate of cognitive decline (Figure 1). The AD PRS was only associated with decline in Ab-positive individuals, but the intelligence PGS was protective irrespective of Ab-status (Figure 2). The model containing only the APOE burden (ε4 and ε2 counts) was associated with cognitive decline with a nominal level of significance, whereas this was not found for the early-stage AD cohort (Figure 1 and 2). Our GWAS identified 8 genes (out of which 3 genes independent of Aβ-status) associated with rate of cognitive decline at a p-value ≤ 5e-05 (Table 1). CONCLUSION: An a priori defined genetic risk score for AD was only associated with rate of cognitive decline in early stage AD (Aβ+ CU and Aβ+ MCI) and not in an unselected population, while a polygenic score for intelligence was protective irrespective of Aβ status. Together with novel genetic associations for rate of cognitive decline in AD, this may provide new insights into the pathophysiology of AD and new therapeutic development targets.
|
|
| 21. |
- Kumar, Atul, et al.
(författare)
-
Genetic interaction study of Alzheimer's disease quantitative biomarkers : A polygenic risk score analysis and evaluation
- 2021
-
Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - 1552-5279. ; 17
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Relationship between genetic factors and pathological features of Alzheimer's disease (AD) may be studied with biomarker, using both polygenic risk scores (PRSs), as well as individual genetic variants in genome-wide association studies (GWAS). METHOD: In the Swedish BioFINDER study, we used a priori PRS for AD based on findings in recent GWAS, and AD related biomarkers in cerebrospinal fluid (CSF) in cognitively unimpaired individuals (n = 751), Mild Cognitive Impairment (n = 212), and AD (n = 150) patients. AD related biomarkers were rank-based inverse normal transformed to be used as dependent variables in linear regression models adjusted for age, gender, education, APOE ε4, ε2 count and significant principal components. We also tested individual genetic variants in GWAS for each biomarker. Analyses were performed in the total sample, and after stratification on MMSE results. RESULT: The PRS was associated with higher CSF P-tau 181 (p ≤1.2e-05) and T-tau (p ≤ 8.14e-05) and lower CSF Aβ42/40 (p ≤ 0.006) and Aβ42 (p ≤ 0.04) (Figure 1, 2). Gene Enrichment of PRS 5 genes [containing 1850 genetic variants mapped to 1607 genes] for Tau biomarker showed 13 Gene Ontology (GO) Biological Process (BP) terms at p-value < e-03 ("Dendrite Morphogenesis": top hit; p-value ≤ 9.20e-06) and 16 KEGG pathway term enriched for genes of PRS 5 ("Phosphatidylinositol signaling system": top hit; p-value ≤ 5.5e-06) (Figure 3, 4). Gene enrichment of PRS 7 [containing 62 genetic variants mapped to 58 genes] for Aβ biomarker returned 12 GO terms ("Integrin-Mediated Signaling Pathway": top hit; p-value ≤1.20e-03) and 1 term enriched for KEGG pathway (Hematopoietic cell lineage). In our predefined list of genes interacting with MAPT (22 genes) and APP (69 genes) we found 3 genes from MAPT and APP set that were involved in PRS 5 and PRS 7 respectively. We also found 9 genes from APP set that was involved in PRS 5. CONCLUSION: Elevated levels of AD related biomarkers are associated with polygenic risk scores in AD. These findings further strengthens the link between genetic and biomarker disease predictors and indicate a potential role for these markers in disease prediction and patient stratification in AD.
|
|
| 22. |
- Kumar, Atul, et al.
(författare)
-
β-Amyloid-Dependent and-Independent Genetic Pathways Regulating CSF Tau Biomarkers in Alzheimer Disease
- 2022
-
Ingår i: Neurology. - 0028-3878. ; 99:5, s. 476-487
-
Tidskriftsartikel (refereegranskat)abstract
- Abnormal metabolism of β-amyloid (Aβ) and soluble phosphorylated tau (P-tau), as well as neurodegeneration, are key components of Alzheimer disease (AD), but it is unclear how these different processes are related to genetic risk factors for AD.MethodsIn the Swedish BioFINDER study, we tested associations between a priori defined polygenic risk scores (PRSs) for AD (excluding single-nucleotide polymorphism [SNP] within the APOE region in the main analysis) and biomarkers in CSF (total tau [T-tau] and P-tau181; Aβ1-38, Aβ1-40, Aβ1-42, and Aβ1-42/1-40; and neurofilament light [NfL]) in cognitively unimpaired (CU) individuals (n = 751), and in patients with mild cognitive impairment (MCI) (n = 212) and AD dementia (n = 150). Results were validated in the Alzheimer's Disease Neuroimaging Initiative data set with 777 individuals (AD = 119, MCI = 442, and CU = 216).ResultsPRSs with SNPs significant at p < 5e-03 (∼1,742 variants) were associated with higher CSF P-tau181 (β = 0.13, p = 5.6e-05) and T-tau (β = 0.12, p = 4.3e-04). The associations between PRS and tau measures were partly attenuated but remained significant after adjusting for Aβ status. Aβ pathology mediated 37% of the effect of this PRS on tau levels. Aβ-dependent and Aβ-independent subsets of the PRS were identified and characterized. There were also associations between PRSs and CSF Aβ biomarkers with nominal significance, but not when corrected for multiple comparisons. There were no associations between PRSs and CSF NfL.DiscussionGenetic pathways implicated in causing AD are related to altered levels of soluble tau through both Aβ-dependent and Aβ-independent mechanisms, which may have relevance for anti-tau drug development.
|
|
| 23. |
- Pereira, Joana B, et al.
(författare)
-
DOPA decarboxylase is an emerging biomarker for Parkinsonian disorders including preclinical Lewy body disease
- 2023
-
Ingår i: Nature Aging. - 2662-8465. ; 3:10, s. 1201-1209
-
Tidskriftsartikel (refereegranskat)abstract
- The diagnosis of Parkinsonian disorders is currently based on clinical criteria, which have limited sensitivity until most dopaminergic neurons are lost. Here we show that cerebrospinal fluid levels of DOPA decarboxylase (DDC) (also known as aromatic L-amino acid decarboxylase) can accurately identify patients with Lewy body disease (LBD) (area under the curve (AUC) = 0.89; PFDR = 2.6 × 10-13) and are associated with worse cognitive performance (P < 0.05). We also found that DDC can detect preclinical LBD stages in clinically unimpaired individuals with a positive seed amplification α-synuclein assay (AUC = 0.81, P = 1.0 × 10-5) and that this biomarker could predict progression to clinical LBD over a 3-year period in preclinical cases (hazard ratio = 3.7 per s.d. change, confidence interval = 1.1-12.7). Moreover, DDC levels were also increased in atypical Parkinsonian disorders but not in non-Parkinsonian neurodegenerative disorders. These cerebrospinal fluid results were replicated in an independent cohort, where we also found that DDC levels in plasma could identify both LBD and atypical Parkinsonian disorders (AUC = 0.92, P = 1.3 × 10-14). Our results show that DDC might have a future role in clinical practice as a biomarker of dopaminergic dysfunction to detect Parkinsonian disorders even during the preclinical disease stages and predict their progression to clinical LBD.
|
|
| 24. |
- Prashar, Atul K., et al.
(författare)
-
In situ synthesis of Pt nanoparticles in SBA-15 by encapsulating in modified template micelles : size restricted growth within the mesochannels
- 2008
-
Ingår i: Journal of Materials Chemistry. - : Royal Society of Chemistry (RSC). - 0959-9428 .- 1364-5501. ; 18:15, s. 1765-1770
-
Tidskriftsartikel (refereegranskat)abstract
- A truly in situ and simple method is developed for nanoparticle incorporation within the mesochannels of SBA-15 involving dispersion of metal precursors in surfactant-modified polymer micelles. The diffusion of the precursor within the micellar structure is aided by interaction with the cationic head group of the surfactant leading to a unique method to facilitate the formation of highly disperse, uniform nanoparticles molded by the walls of the mesochannels. The nanoparticle incorporated mesoporous material has a highly enhanced surface area and adsorption capabilities in comparison to its parent materials without any pore blockage which makes this method ideal for the preparation of nanocatalysts.
|
|
| 25. |
- Quigley, David A, et al.
(författare)
-
Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer
- 2016
-
Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 16:4, s. 65-1153
-
Tidskriftsartikel (refereegranskat)abstract
- Inherited germline polymorphisms can cause gene expression levels in normal tissues to differ substantially between individuals. We present an analysis of the genetic architecture of normal adult skin from 470 genetically unique mice, demonstrating the effect of germline variants, skin tissue location, and perturbation by exogenous inflammation or tumorigenesis on gene signaling pathways. Gene networks related to specific cell types and signaling pathways, including sonic hedgehog (Shh), Wnt, Lgr family stem cell markers, and keratins, differed at these tissue sites, suggesting mechanisms for the differential susceptibility of dorsal and tail skin to development of skin diseases and tumorigenesis. The Pten tumor suppressor gene network is rewired in premalignant tumors compared to normal tissue, but this response to perturbation is lost during malignant progression. We present a software package for expression quantitative trait loci (eQTL) network analysis and demonstrate how network analysis of whole tissues provides insights into interactions between cell compartments and signaling molecules.
|
|
| 26. |
- Sao, Prachi, et al.
(författare)
-
Potential drug target identification in porphyromonas gingivalis using in-silico subtractive metabolic pathway analysis
- 2021
-
Ingår i: Bangladesh Journal of Medical Science. - : Bangladesh Journals Online (JOL). - 2223-4721 .- 2076-0299. ; 20:4, s. 887-896
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Porphyromonas Gingivalis (P. gingivalis) a primary periodontal disease pathogen. This bacterium affects sub-gingival tissue and leads to loss of teeth and alveolar bone destruction in the acute stage. In recent years, P. gingivalis is often connected with other diseases such as rheumatoid arthritis, diabetes, Alzheimer’s, and heart disease, though the aetiology is still unclear. Objective: The use of commonly available drugs to treat periodontitis results in various side effects, in particular multi-drug resistant strains. As the development of multidrug-resistant strains frequently urges the identification of novel drug targets, the aim of this study is to identify specific targets in the narrow spectrum to combat oral pathogens. Methodology: This study used a comparative and subtractive pathway analysis approach to identify potential drug targets specific to P. gingivalis. Results: The in-silico comparison of the P. gingivalis and Homo sapiens (H. sapiens) metabolic pathways resulted in 13 unique pathogen pathways. A homology search of the 67 enzymes in the unique bacterial pathway using the BLASTp program against the Homo sapiens proteome resulted in fifteen possible targets that are non-homologous to the human proteome. Thirteen genes among 15 potent target encoders are key DEG genes indispensable for P. gingivalis’s survival. A comprehensive analysis of the literature identified three potential therapeutic drug targets. Conclusions: The three most relevant drug targets are Arabinose-5-phosphate isomerase, UDP-2,3-diacylglucosamine hydrolase, and Undecaprenyl diphosphatase. Upon corroboration, these targets may give rise to narrow-spectrum antibiotics that can specificallytreat thedental infection.
|
|
| 27. |
- Sharma, Atul, et al.
(författare)
-
Intracellular Locations of Replication Proteins and the Origin of Replication during Chromosome Duplication in the Slowly Growing Human Pathogen Helicobacter pylori
- 2014
-
Ingår i: Journal of Bacteriology. - 0021-9193 .- 1098-5530. ; 196:5, s. 999-1011
-
Tidskriftsartikel (refereegranskat)abstract
- We followed the position of the replication complex in the pathogenic bacterium Helicobacter pylori using antibodies raised against the single-stranded DNA binding protein (HpSSB) and the replicative helicase (HpDnaB). The position of the replication origin, oriC, was also localized in growing cells by fluorescence in situ hybridization (FISH) with fluorescence-labeled DNA sequences adjacent to the origin. The replisome assembled at oriC near one of the cell poles, and the two forks moved together toward the cell center as replication progressed in the growing cell. Termination and resolution of the forks occurred near midcell, on one side of the septal membrane. The duplicated copies of oriC did not separate until late in elongation, when the daughter chromosomes segregated into bilobed nucleoids, suggesting sister chromatid cohesion at or near the oriC region. Components of the replication machinery, viz., HpDnaB and HpDnaG (DNA primase), were found associated with the cell membrane. A model for the assembly and location of the H. pylori replication machinery during chromosomal duplication is presented.
|
|
| 28. |
- Singh, Anirudh, et al.
(författare)
-
Computational Study on Parametric Variation with Solar Heat Induction of an Entrained Flow Gasifier
- 2022
-
Ingår i: Energies. - : MDPI AG. - 1996-1073. ; 15:11
-
Tidskriftsartikel (refereegranskat)abstract
- Gasification has played an important role in the sustainable use of waste biomass, providing useful combustible gases in the process. Gasification has an important role in waste management and promotes energy independence for many oil-deficit countries. The gasification process has been studied by various researchers, and improvements have been achieved in its sub-processes such as devolatilization, feed input methods, and so on. We examined the influence of gasifier operation parameters, such as oxidizer content, moisture content in the feedstock, and solar flux input inside the gasifier, on the temperature distribution, velocity distribution, and product gas yields of the gasifier. The results indicate that inducing solar energy at different stages of the gasifier leads to different yields of product gas composition (CO and H-2).
|
|
| 29. |
- Srivastava, Manu, et al.
(författare)
-
A review of various materials for additive manufacturing : Recent trends and processing issues
- 2022
-
Ingår i: Journal of materials research and technology. - : Elsevier. - 2238-7854. ; 21, s. 2612-2641
-
Tidskriftsartikel (refereegranskat)abstract
- Tremendous growth has been witnessed in the field of additive manufacturing (AM) technology over the last few decades. It offers a plethora of applications and is already being utilized in almost every sphere of life. Owing to inherent differences between each AM technique, newer fields of research consistently emerge and demand attention. Also, the innovative applications of AM open up newer challenges and thus avenues for focused attention. One such avenue is AM materials. Raw material plays an important role in determining the properties of fabricated part. The type and form of raw material largely depend on the type of AM fabricators. There is a restriction on material compatibility with most of the established AM techniques. This review aims to provide an overview of various aspects of AM materials highlighting the progress made especially over the past two decades.
|
|
| 30. |
- Sunny, Jithin S., et al.
(författare)
-
Converting the genomic knowledge base to build protein specific machine learning prediction models; a classification study on thermophilic serine protease
- 2022
-
Ingår i: Biologia. - : Springer Science and Business Media LLC. - 0006-3088 .- 1336-9563. ; 77:12, s. 3615-3622
-
Tidskriftsartikel (refereegranskat)abstract
- Several machine learning models have been formulated for protein classification based on an important prerequisite for industrial usage, thermostability, and described herein a classification model for a specific enzyme; serine protease. For building the classifier, 283 thermophilic and 200 mesophilic bacterial genomes were mined for their respective serine protease sequences. Features were extracted from 760 sequences, followed by feature selection. We deployed a random forest-based classifier that identified thermophilic and non-thermophilic serine proteases with an accuracy of 97.11%, higher than other benchmark machine learning methods. Knowledge of thermostability and amino acid positional shifts can be vital for downstream protein engineering techniques. Thus, a web platform has been proposed to emphasize the real-time application of this enzyme-specific classification model. We designed a framework that can aid protein engineers in combining their sequence data and the classification model and employ it to align query sequences against the custom databases and identify similar novel enzymes along with their thermophilic nature.
|
|
| 31. |
- Tiwari, Atul, et al.
(författare)
-
Biopolymers : An Indispensable Tool for Biotechnology
- 2012
-
Ingår i: Biotechnology in Biopolymers. - United Kingdom : Smithers Rapra. - 9781847355423 ; , s. 1-16
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This comprehensive book provides up-to-date information on the developments in the field of biopolymers. Close attention has been paid to include all the important aspects that are necessary to understand the field. The book introduces the reader with the progress in the field, followed by outlining its applications in different areas. Different methods and techniques of synthesis and characterization are detailed as individual chapters. Various mode and mechanism of degradation of materials will be discussed. There is a dedicated chapter on industrially available biopolymers and their applications and well as a chapter detailing the ongoing research, current trends and future challenges.
|
|
