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  • Article
    Fahmy HA, El-Shamy S, Farag MA.
    Sci Rep. 2023 10 25;13(1):18221.
    Exploring novel sources of plant protein for nutrition of both humans and animals is motivated mainly by its growing demand worldwide, besides identifying healthy alternatives for animal protein. The present study evaluates metabolome diversity within 15 legume seed species. The examined samples comprised three Melilotus, four Medicago, four Trifolium, and four Ononis seed species. A holistic approach for metabolites profiling using gas chromatography-mass spectrometry (GC-MS) led to the annotation and quantification of 87 metabolites comprising alcohols, free amino acids, aromatics, fatty acids/esters, nitrogenous compounds, organic acids, sugar alcohols, sugars, terpenes, and steroids. Fatty acids represented the major metabolite class represented by palmitic, stearic, oleic, linoleic, and linolenic acids. Sucrose and pinitol were the major sugars and sugar alcohols among seeds. Ononis seeds (OR, OS and OA) were the most abundant in fatty acids, sugars, sugar alcohols, and free amino acids, whereas Melilotus species (MO and MS) were least enriched in these key nutrients posing Ononis as potential food source for humans and animals. The examined seeds were generally low in sulfur-containing free amino acids and lacking many of the essential free amino acids. Multivariate data analysis aided in the identification of Ononis metabolite markers belonging to various classes i.e., (alcohol) glycerol, (sugar) allofuranose, and (sugar alcohol) pinitol, although the differentiation between Medicago, Melilotus, and Trifolium genera was not attained suggestive for other analytical platforms for its classification.
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  • Article
    Lago D, Kraxner J, Galusek D, Bernardo E.
    Heliyon. 2023 Aug;9(8):e18221.
    A porous membrane was developed through alkali activation of pharmaceutical boro-alumino-silicate glass powders suspended in diluted NaOH and KOH aqueous solutions (2.5 M). A consolidated porous structure was obtained by the binding of unreacted particles mediated by a surface gel, developed upon drying of the suspensions and their curing at 40 °C for 14 days. The binding phase was sufficiently stable to resist immersion in boiling water and in acidic solutions. Copper adsorption tests were carried out under acidic pH, immersing the membranes in a Cu(NO3)2 solution for different periods of time. To determine the effect of surface washing on capture of copper ions, adsorption experiments with washed and unwashed membranes were also carried out, at varying pH. It was determined that the adsorption kinetics follow the pseudo-second-order kinetic model. The main adsorption mechanism observed is the electrostatic interaction between the negative surface charge of the washed membrane and the Cu2+ ions present in solution. An adsorption higher than 60% was observed at pH = 5, while at pH = 2 the efficiency decreased due to the presence of H3O+ ions. To ensure immobilization of copper, the membranes were densified by viscous flow sintering at a moderate temperature (700 °C). Leaching tests on membranes demonstrated the efficiency of the process in terms of copper ions immobilization.
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  • Article
    Rastad H, Qorbani M, Pourrostami K, Ochi F, Sheidayi A, Ejtahed HS, Seif E, Mohammadian Khonsari N, Mahdavi-Gorabi A, Heshmat R, Kelishadi R.
    Sci Rep. 2022 10 29;12(1):18221.
    The number of single-child families has been increasing across developing countries during the last decades. We aimed to examine the association between being a single child (SC) and subjective health complaints (SHCs) in Iranian children and adolescents. This study was conducted as a part of the fifth survey of a national surveillance program entitled Childhood and Adolescence Surveillance and Prevention of Adult Non-communicable disease (CASPIAN-V). This national survey included a total of 14,400 students 7-18 years and their parents from rural and urban areas in 30 provinces of Iran. Data on demographic characteristics, lifestyle variables, and SHCs were measured using the questionnaire of the World Health Organization on Global School-based Health Survey (WHO-GSHS). Multivariate logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95%CI) for the association of being an SC with SHCs. Data on 14,151 participants were available for this study, of whom 7.7% (1092) were SCs. The most frequent SHCs were irritability (37.1%, 95%CI: 36.3-37.9%), feeling nervous 32.5%, 95% CI: (31.7-33.3%), and headache 24.3%, 95%CI: (23.6-25.0% ). In the multivariate model, being an SC significantly increased the odds of dizziness [adjusted OR (95% CI): 1.37(1.08-1.72)] and backache complaint [1.22(1.01-1.47)]. The association of being an SC with other SHCs (feeling low, irritability, feeling nervous, difficulty in getting to sleep, headache, stomachache) was not statistically significant (p value > 0.05). Our results suggest that being an SC may be associated with higher odds of dizziness and backache complaints.
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  • Article
    Liou YJ, Chen MH, Hsu JW, Huang KL, Huang PH, Bai YM.
    Sci Rep. 2021 09 14;11(1):18221.
    The association of major depressive disorder (MDD) with cardiovascular diseases (CVDs) through endothelial dysfunction is bidirectional. Circulating endothelial progenitor cells (cEPCs), essential for endothelial repair and function, are associated with risks of various CVDs. Here, the relationship of cEPC counts with MDD and the related clinical presentations were investigated in 50 patients with MDD and 46 healthy controls. In patients with MDD, a battery of clinical domains was analysed: depressed mood with Hamilton Depression Rating Scale (HAMD) and Montgomery-Åsberg Depression Rating Scale (MADRS), anxiety with Hamilton Anxiety Rating Scale (HAMA), cognitive dysfunction and deficit with Digit Symbol Substitution Test (DSST) and Perceived Deficits Questionnaire-Depression (PDQ-D), somatic symptoms with Depressive and Somatic Symptom Scale (DSSS), quality of life with 12-Item Short Form Health Survey (SF-12) and functional disability with Sheehan Disability Scale (SDS). Immature and mature cEPC counts were measured through flow cytometry. Increased mature and immature cEPC counts were significantly associated with higher anxiety after controlling the confounding effect of systolic blood pressure, and potentially associated with more severe depressive symptoms, worse cognitive performance and increased cognitive deficit, higher social disability, and worse mental health outcomes. Thus, cEPCs might have pleiotropic effects on MDD-associated symptoms and psychosocial outcomes.
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  • Article
    Singh BM, Bohara N, Gautam K, Basnet M, Kc S, Kc B, Raut A, Phudong A, Gautam J.
    Cureus. 2021 Sep;13(9):e18221.
    Transthyretin amyloid cardiomyopathy disease burden is increasing daily due to advancements in diagnostic and imaging modalities in the modern world. Tafamidis is one of many therapeutic options. The main objective of this review is to study the role of Tafamidis in slowing the progression of transthyretin cardiomyopathy (TTR-CM) by analyzing randomized controlled trials (RCTs) and non-RCTs of Tafamidis. We searched for published papers of Tafamidis in the English language in electronic databases like Google Scholar, PubMed, Cochrane Library, and PubMed Central. We imported the resulting articles from our search to Mendeley software. Four reviewers removed the duplicates and performed title and abstract screening of the articles. The same reviewers obtained the full-text of relevant articles and did full-text screening based on eligibility criteria. Finally, five reviewers performed a quality assessment of RCTs using the Cochrane risk of bias assessment and of non-RCTs by a checklist prepared by Downs and Black. Any disagreements about any process were resolved by a discussion with other authors. One RCT and five non-RCTs of Tafamidis were included in this systematic review. From the non-RCTs, stability was observed in different parameters like echocardiographic findings, cardiac biomarkers, and ECG in patients with transthyretin cardiomyopathy during the study duration with Tafamidis. ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial) trial demonstrated reduction of cardiovascular events and all-cause mortality in the Tafamidis group in comparison to placebo. In both RCT and non-RCTs, Tafamidis was established as a safe and tolerable drug for patients with TTR-CM. Our study proved the role of Tafamidis in reducing cardiovascular events, all-cause mortality, and the progression of cardiac disease in TTR-CM patients. In addition to five non-RCTs, current evidence is based on the findings of only one RCT of Tafamidis. Hence, evidence from additional RCTs is required to strongly support the stability of parameters like echocardiographic findings, cardiac biomarkers, and ECG with Tafamidis use.
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  • Article
    Chaín JM, Tubert E, Graciano C, Castagno LN, Recchi M, Pieckenstain FL, Estrella MJ, Gudesblat G, Amodeo G, Baroli I.
    Sci Rep. 2020 10 26;10(1):18221.
    Eucalyptus grandis is a globally important tree crop. Greenhouse-grown tree seedlings often face water deficit after outplanting to the field, which can affect their survival and establishment severely. This can be alleviated by the application of superabsorbent hydrophilic polymers (SAPs). Growth promoting bacteria can also improve crop abiotic stress tolerance; however, their use in trees is limited, partly due to difficulties in the application and viability loss. In this work, we evaluated the improvement of drought tolerance of E. grandis seedlings by inoculating with two Pseudomonas strains (named M25 and N33), carried by an acrylic-hydrocellulosic SAP. We observed significant bacterial survival in the seedling rhizosphere 50 days after inoculation. Under gradual water deficit conditions, we observed a considerable increase in the water content and wall elasticity of M25-inoculated plants and a trend towards growth promotion with both bacteria. Under rapid water deficit conditions, which caused partial defoliation, both strains significantly enhanced the formation of new leaves, while inoculation with M25 reduced the transpiration rate. Co-inoculation with M25 and N33 substantially increased growth and photosynthetic capacity. We conclude that the selected bacteria can benefit E. grandis early growth and can be easily inoculated at transplant by using an acrylic-hydrocellulosic SAP.
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  • Article
    Agre P, Asibe F, Darkwa K, Edemodu A, Bauchet G, Asiedu R, Adebola P, Asfaw A.
    Sci Rep. 2019 12 03;9(1):18221.
    A better understanding of the structure and extent of genetic variability in a breeding population of a crop is essential for translating genetic diversity to genetic gain. We assessed the nature and pattern of genetic variability and differentiation in a panel of 100 winged-yam (Dioscorea alata) accessions using 24 phenotypic traits and 6,918 single nucleotide polymorphism (SNP) markers. Multivariate analysis for phenotypic variability indicated that all phenotypic traits assessed were useful in discriminating the yam clones and cultivars. Cluster analysis based on phenotypic data distinguished two significant groups, while a corresponding analysis with SNP markers indicated three genetic groups. However, joint analysis for the phenotypic and genotypic data provided three clusters that could be useful for the identification of heterotic groups in the D. alata breeding program. Our analysis for phenotypic and molecular level diversity provided valuable information about overall diversity and variation in economically important traits useful for establishing crossing panels with contrasting traits of interest. The selection and hybridization of parental lines from the different heterotic groups identified would facilitate maximizing diversity and exploiting population heterosis in the D. alata breeding program.
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  • Article
    Trifan A, Stanciu C, Jurcău M, Zenovia S, Frunzuc G, Timofte D.
    Medicine (Baltimore). 2019 Dec;98(50):e18221.
    BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a subtype of non-alcoholic fatty liver disease (NAFLD) with a potentially progressive course to liver fibrosis, cirrhosis with its complications, or even hepatocellular carcinoma. NAFLD is a rapidly growing chronic liver disease, with a global prevalence of about 25%, with a significant increase in the last 2 decades, changing the landscape of hepatology. This study aimed to undertake a bibliometric global analysis of research literature focusing on NASH.
    METHODS: We searched the Scopus database to identify all articles pertaining to "non-alcoholic steatohepatitis" or "NASH" - the 2 keywords used to search in the title or abstract within the time period 1980 to 2018. The collected data included document type, author, journal, publication year, citation reports, country, and were analyzed using Microsoft Excel and Microsoft Word.
    RESULTS: A total number of 6632 articles published in 1355 journals were retrieved. English was the predominant language of publication, USA being the most productive with 1937 articles published (29.2% of the total number of publications), followed by Japan with 909, representing 13.7% of publications. Hepatology, Journal of Hepatology and World Journal of Gastroenterology were the most active journals. Research articles were the most common type of publications (4524; 68.22%), followed by review articles (1359; 20.49%). The total number of citations received by all publications was 274,041, with an average of 41.32 per article (range: 0-4384). The average number of authors per article has increased in the last 2 decades, whereas the trend of single- (or few) authored publications has decreased.
    CONCLUSION: This study indicates that NASH is a significant topic in the hepatology research, as proved by the huge number of publications, recording an exponential growth in the last 2 decades. The USA stands out as by far the most productive country.
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  • Article
    Gierse LC, Meene A, Schultz D, Schwaiger T, Schröder C, Mücke P, Zühlke D, Hinzke T, Wang H, Methling K, Kreikemeyer B, Bernhardt J, Becher D, Mettenleiter TC, Lalk M, Urich T, Riedel K.
    Microbiol Spectr. 2021 10 31;9(2):e0018221.
    Seasonal influenza outbreaks represent a large burden for the health care system as well as the economy. While the role of the microbiome has been elucidated in the context of various diseases, the impact of respiratory viral infections on the human microbiome is largely unknown. In this study, swine was used as an animal model to characterize the temporal dynamics of the respiratory and gastrointestinal microbiome in response to an influenza A virus (IAV) infection. A multi-omics approach was applied on fecal samples to identify alterations in microbiome composition and function during IAV infection. We observed significantly altered microbial richness and diversity in the gastrointestinal microbiome after IAV infection. In particular, increased abundances of Prevotellaceae were detected, while Clostridiaceae and Lachnospiraceae decreased. Moreover, our metaproteomics data indicated that the functional composition of the microbiome was heavily affected by the influenza infection. For instance, we identified decreased amounts of flagellin, correlating with reduced abundances of Lachnospiraceae and Clostridiaceae, possibly indicating involvement of a direct immune response toward flagellated Clostridia during IAV infection. Furthermore, enzymes involved in short-chain fatty acid (SCFA) synthesis were identified in higher abundances, while metabolome analyses revealed rather stable concentrations of SCFAs. In addition, 16S rRNA gene sequencing was used to characterize effects on the composition and natural development of the upper respiratory tract microbiome. Our results showed that IAV infection resulted in significant changes in the abundance of Moraxellaceae and Pasteurellaceae in the upper respiratory tract. Surprisingly, temporal development of the respiratory microbiome structure was not affected. IMPORTANCE Here, we used swine as a biomedical model to elucidate the impact of influenza A H1N1 infection on structure and function of the respiratory and gastrointestinal tract microbiome by employing a multi-omics analytical approach. To our knowledge, this is the first study to investigate the temporal development of the porcine microbiome and to provide insights into the functional capacity of the gastrointestinal microbiome during influenza A virus infection.
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  • Article
    Tian H, Zhang Y, Han J, Xu Z, Zhang X, Liu S, Wang C, Yang Y, Han L, Yang J.
    Nanoscale. 2016 Oct 27;8(42):18221-18227.
    Nd2Fe14B/α-Fe nanocomposite magnets are prepared through electron beam exposure with a greatly reduced annealing time of 0.1 s. This is by far the most effective approach due to the effect of an extremely high heating rate featuring a rapid thermal process. The impact that the rapid thermal process has on crystallization is expounded by the introduction of the Landau model and Langevin dynamical simulations. The change of crystallization sequence from the α-Fe phase preceding the Nd2Fe14B phase under conventional annealing conditions, to synergetic crystallization under electron beam conditions is investigated. Synergetic crystallization results in more intense interaction between the α-Fe phase and the Nd2Fe14B phase in order to refine the microstructure as the fraction of Fe increases within our addition range. Improved uniformity, and shifts in the microstructure and distribution of the α-Fe phase contribute to the improvement of the magnetic properties. Compared with conventional furnace annealing ones, the magnetic properties of samples under electron beam exposure conditions are improved. For the Nd10Fe83.3B6.2Nb0.2Ga0.3 alloy, coercivity is enhanced from 4.56 kOe to 6.73 kOe, remanence ratio increases from 0.75 to 0.79, and a superior squareness of the hysteresis loop is achieved.
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  • Article
    Mohsen Dehnavi S, Pazuki G, Vossoughi M.
    Sci Rep. 2015 Dec 14;5:18221.
    High resolution is nearly lost at the expense of throughput in most conventional bioseparation methods. Nanoparticles, due to their high surface to volume ratio, are attractiveenzyme carriers, which can boost the performance of extraction manifold. Here, wereport design and application ofa method highly capable of improving the partitioning of α-amylase in aqueous two-phase system of polymer and salt. Silica nanoparticle introduced to the system acts as a bridge that connects the enzyme and polymer. Theconjugated nanoparticles form the major part of the upper phase and thus significantly enhance the protein recovery. A thorough investigation was performed on the structure of the nanoconjugatesas well as analyzing the conformational structure of the enzyme after conjugationto explore anypossible denaturation.
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  • Article
    Hardeland R.
    Int J Mol Sci. 2014 Oct 10;15(10):18221-52.
    Melatonin is a highly pleiotropic regulator molecule, which influences numerous functions in almost every organ and, thus, up- or down-regulates many genes, frequently in a circadian manner. Our understanding of the mechanisms controlling gene expression is actually now expanding to a previously unforeseen extent. In addition to classic actions of transcription factors, gene expression is induced, suppressed or modulated by a number of RNAs and proteins, such as miRNAs, lncRNAs, piRNAs, antisense transcripts, deadenylases, DNA methyltransferases, histone methylation complexes, histone demethylases, histone acetyltransferases and histone deacetylases. Direct or indirect evidence for involvement of melatonin in this network of players has originated in different fields, including studies on central and peripheral circadian oscillators, shift work, cancer, inflammation, oxidative stress, aging, energy expenditure/obesity, diabetes type 2, neuropsychiatric disorders, and neurogenesis. Some of the novel modulators have also been shown to participate in the control of melatonin biosynthesis and melatonin receptor expression. Future work will need to augment the body of evidence on direct epigenetic actions of melatonin and to systematically investigate its role within the network of oscillating epigenetic factors. Moreover, it will be necessary to discriminate between effects observed under conditions of well-operating and deregulated circadian clocks, and to explore the possibilities of correcting epigenetic malprogramming by melatonin.
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  • Article
    Corkett AJ, Chen Z, Ertural C, Slabon A, Dronskowski R.
    Inorg Chem. 2022 Nov 14;61(45):18221-18228.
    Quaternary transition metal cyanamides Na2MSn2(NCN)6 with M = Mn, Fe, Co, and Ni were prepared via solid-state metathesis reactions between Na2Sn(NCN)3 and binary transition metal fluorides MF2 in a 2:1 molar ratio. All phases crystallize isotypically in [NiAs]-derived structures (P3̅1m) with inter- and intra-layer cation ordering over the octahedral sites. This leads to a highly asymmetric coordination of the NCN2- anion, resulting in a strong degree of cyanamide character, which is confirmed via IR measurements. Intriguingly, the optical properties of Na2MSn2(NCN)6 phases change markedly as the nature of the divalent transition metal is varied, and UV-vis measurements evidence a band gap reduction from Mn (3.43 eV) via Fe (1.90 eV) to Co (1.75 eV), which broadly mirrors the DFT+U calculated energetic interval from the Fermi level to the unoccupied 3d states. Mott-Schottky analysis then goes on to characterize Na2FeSn2(NCN)6 and Na2CoSn2(NCN)6 as n-type semiconductors with flat-band potentials of 0.46 and -0.24 eV, respectively, vs RHE. This study demonstrates the utility of transition metal substitutions, within a flexible cyanamide framework, to electronically tune this growing family of pseudo-oxides.
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  • Article
    Alvarez-Fernandez M, Liang YH, Abrahamson M, Su XD.
    J Biol Chem. 2005 May 06;280(18):18221-8.
    Cystatins are natural inhibitors of papain-like (family C1) and legumain-related (family C13) cysteine peptidases. Cystatin D is a type 2 cystatin, a secreted inhibitor found in human saliva and tear fluid. Compared with its homologues, cystatin D presents an unusual inhibition profile with a preferential inhibition cathepsin S > cathepsin H > cathepsin L and no inhibition of cathepsin B or pig legumain. To elucidate the structural reasons for this specificity, we have crystallized recombinant human Arg(26)-cystatin D and solved its structures at room temperature and at cryo conditions to 2.5- and 1.8-A resolution, respectively. Human cystatin D presents the typical cystatin fold, with a five-stranded anti-parallel beta-sheet wrapped around a five-turn alpha-helix. The structures reveal differences in the peptidase-interacting regions when compared with other cystatins, providing plausible explanations for the restricted inhibitory specificity of cystatin D for some papain-like peptidases and its lack of reactivity toward legumain-related enzymes.
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  • Article
    Lazarov B, Swinnen R, Spruyt M, Maes F, Van Campenhout K, Goelen E, Covaci A, Stranger M.
    Environ Sci Pollut Res Int. 2015 Nov;22(22):18221-9.
    An analytical methodology using automatic thermal desorption and gas chromatography mass spectrometry analysis was optimized and validated for simultaneous determination of a set of components from three different flame retardant chemical classes: polybrominated diphenyl ethers (PBDEs) (PBDE-28, PBDE-47, PBDE-66, PBDE-85, PBDE-99, PBDE-100), organophosphate flame retardants (PFRs) (tributyl phosphate, tripropyl phosphate, tris(2-chloroethyl)phosphate-, tris(1,3-dichloro-2-propyl) phosphate, tris(2-ethylhexyl) phosphate, triphenyl phosphate, tris(2-chloro-1-methylethyl) phosphate and tricresylphosphate), and "novel" brominated flame retardants (NBFRs) (pentabromotoluene, 2,3,4,5,6-pentabromoethylbenzene, (2,3-dibromopropyl) (2,4,6-tribromophenyl) ether, hexabromobenzene, and 2-ethylhexyl 2,3,4,5-tetrabromobenzoate) in air. The methodology is based on low volume active air sampling of gaseous and particulate air fractions on mixed-bed (polydimethylsiloxane (PDMS)/Tenax TA) sorption tubes. The optimized method provides recoveries >88%; a limit of detection in the range of 6-25 pg m(-3) for PBDEs, 6-171 pg m(-3) for PFRs, and 7-41 pg m(-3) for NBFRs; a linearity greater than 0.996; and a repeatability of less than 10% for all studied compounds. The optimized method was compared with a standard method using active air sampling on XAD-2 sorbent material, followed by liquid extraction. On the one hand, the PDMS/Tenax TA method shows comparable results at longer sampling time conditions (e.g., indoor air sampling, personal air sampling). On the other hand, at shorter sampling time conditions (e.g., sampling from emission test chambers), the optimized method detects up to three times higher concentrations and identifies more flame retardant compounds compared to the standard method based on XAD-2 loading.
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  • Article
    Walter SA, Cutler RE, Martinez R, Gishizky M, Hill RJ.
    J Biol Chem. 2003 May 16;278(20):18221-8.
    The Ste20 family of serine/threonine kinases plays an important role in numerous cellular functions such as growth, apoptosis, and morphogenesis. We have identified a previously cloned but uncharacterized family member termed Stk10, which is a human homolog of murine Lok, a serine/threonine kinase highly expressed in lymphocytes. Northern analysis demonstrated that the Stk10 transcript is present in many tissues, although highest expression levels are seen in hematopoietic cells. Due to close sequence homology to human Slk and Xenopus laevis xPlkk1, two polo-like kinase kinases, we investigated whether Stk10 might also play a role as a Plk1 activator. Plk1 has been shown to be overexpressed in multiple tumor types, thus attracting high interest to its potential upstream regulators. We show here that Stk10 can associate with Plk1 in cells and furthermore can phosphorylate Plk1 in vitro. Engineered NIH-3T3 cell lines that overexpress a dominant negative version of Stk10 display an altered cell cycle phenotype characterized by increased DNA content, raising the possibility that expression of a dominant negative Stk10 may impinge upon Plk1 function in vivo; it has previously been shown that unregulated expression of Plk1 can result in a variety of nuclear defects. We suggest, therefore, that Stk10 is a novel polo-like kinase kinase that cooperates with hSlk to regulate Plk1 function in human cells.
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  • Article
    Shi WY, Wang ZT, Sun FR, Ma YH, Xu W, Shen XN, Dong Q, Tan L, Yu JT, Yu Y, Alzheimer’s Disease Neuroimaging Initiative.
    Aging (Albany NY). 2020 Sep 22;12(18):18221-18237.
    It has been increasingly evident that pulse pressure (PP) is associated with Alzheimer's disease (AD) but whether PP increases AD risk and the mechanism responsible for this association remains unclear. To investigate the effects of PP in the process of AD, we have evaluated the cross-sectional and longitudinal associations of PP with AD biomarkers, brain structure and cognition and have assessed the effect of PP on AD risk in a large sample (n= 1,375) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Multiple linear regression and mixed-model regression were employed in cross-sectional and longitudinal analyses respectively. Clinical disease progression was assessed using Cox proportional hazards models. High PP was associated with lower β-amyloid 42 (Aβ42) (P= .015), and higher total tau (T-tau) (P= .011), phosphorylated tau (P-tau) (P= .003), T-tau/Aβ42 (P= .004) and P-tau/Aβ42 (P = .001), as well as heavier cortical amyloid-beta burden (P= .011). Longitudinally, baseline high PP was significantly associated with hippocampal atrophy (P= .039), entorhinal atrophy (P= .031) and worse memory performance (P= .058). Baseline high PP showed more rapid progression than those with normal PP (P <.001). These results suggest PP elevation could increase AD risk, which may be driven by amyloid plaques and subclinical neurodegeneration.
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  • Article
    Podjed N, Modec B, Alcaide MM, López-Serrano J.
    RSC Adv. 2020 May 10;10(31):18200-18221.
    A seemingly simple combination of [Zn(quin)2(H2O)] (quin- = quinaldinate) and a selected secondary cyclic amine, piperidine (pipe), pyrrolidine (pyro) or morpholine (morph), afforded in acetonitrile a number of products: anionic homoleptic quinaldinate, neutral heteroleptic quinaldinate/amine and quinaldinate/amidine complexes. The piperidine and pyrrolidine systems underwent reaction with acetonitrile to give amidines. The in situ formed piperidinoacetamidine (pipeam) or pyrrolidinoacetamidine (pyroam) coordinated to zinc(ii). Reactions with piperidine led to trans-[Zn(quin)2(pipe)2]·2CH3CN (1), [Zn(quin)2(pipe)]·cis-[Zn(quin)2(pipe)2] (2), pipeH[Zn(quin)3]·CH3CN (3), [Zn(quin)2(pipeam)]·CH3CN (4a), [Zn(quin)2(pipeam)]·2CHCl3 (4b), pipeamH[Zn(quin)3] (5) and pipeamH[Zn(quin)2(CH3COO)]·acetamide (6) (pipeH+ and pipeamH+ denote protonated amine or amidine). By analogy, [Zn(quin)2(pyro)2] (7), pyroH[Zn(quin)3]·CH3CN (8), pyroH[Zn(quin)2Cl] (9), [Zn(quin)2(pyroam)]·CH3CN·0.5pyroam·0.5H2O (10a), [Zn(quin)2(pyroam)]·2CHCl3 (10b), [Zn(quin)2(pyroam)]·CH2Cl2 (10c) and pyroamH[Zn(quin)3] (11) were obtained in the pyrrolidine reactions. The morpholine system allowed isolation of only two novel products, trans-[Zn(quin)2(morph)2] (12) and morphH[Zn(quin)3]·CH3CN (13). Importantly, no amidine could be isolated. Instead, in autoclaves at 105 °C morpholine degraded to ammonia, as confirmed by mass spectrometry of the gas phase. pyroamH[Zn(quin)3] exists in two polymorphs which differ in the binding modes of quinaldinate ligands. In 11triclinic, the metal ion of [Zn(quin)3]- features a five-coordinate environment, whereas that in 11monoclinic is surrounded by six donors. Stabilities of the [Zn(quin)3]- isomers were assessed with DFT calculations. The one with a six-coordinate zinc(ii) ion was found to be more stable than its five-coordinate counterpart. Favorable intermolecular interactions in the solid state stabilize both and reduce the energy difference between them. The calculations show the conversion of the five-coordinate [Zn(quin)3]- into its coordinatively saturated isomer to be an almost barrierless process.
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  • Article
    Dean D, Swaminathan S, Kama M, Goemans S, Faktaufon D, Alnabelseya N, Spelke D, Kahrizi K, Black M, Mitra D.
    J Clin Microbiol. 2021 06 18;59(7):e0018221.
    Rapid and precise detection of Chlamydia trachomatis, the leading global cause of sexually transmitted infections (STI), at the point of care (POC) is required for treatment decisions to prevent transmission and sequelae, including pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, and preterm birth. We developed a rapid POC test (POCT), termed LH-POCT, which uses loop-mediated amplification (LAMP) of nucleic acids. We performed a head-to-head comparison with the Cepheid Xpert CT/NG assay using clinician-collected, deidentified paired vaginal samples from a parent study that consecutively enrolled symptomatic and asymptomatic females over 18 years of age from the Ministry of Health and Medical Services Health Centers in Fiji. Samples were processed by the Xpert CT/NG assay and LH-POCT, blinded to the comparator. Discrepant samples were resolved by quantitative PCR. Deidentified clinical data and tests for Trichomonas vaginalis, Candida, and bacterial vaginosis (BV) were provided. There were a total of 353 samples from 327 females. C. trachomatis positivity was 16.7% (59/353), while the prevalence was 16.82% (55/327) after discrepant resolution. Seven discrepant samples resolved to four false negatives, two false positives, and one true positive for the LH-POCT. The sensitivity of the LH-POCT was 93.65% (95% confidence interval [CI], 84.53% to 98.24%), and specificity was 99.31% (95% CI, 97.53% to 99.92%). Discrepant samples clustered among women with vaginal discharge and/or BV. The prototype LH-POCT workflow has excellent performance, meeting many World Health Organization ASSURED criteria for POC tests, including a sample-to-result time of 35 min. Our LH-POCT holds promise for improving clinical practice to prevent and control C. trachomatis STIs in diverse health care settings globally.
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  • Article
    Amdursky N, Pecht I, Sheves M, Cahen D.
    J Am Chem Soc. 2012 Nov 07;134(44):18221-4.
    Electrons can migrate via proteins over distances that are considered long for nonconjugated systems. The nanoscale dimensions of proteins and their enormous structural and chemical flexibility makes them fascinating subjects for exploring their electron transport (ETp) capacity. One particularly attractive direction is that of tuning their ETp efficiency by "doping" them with small molecules. Here we report that binding of retinoate (RA) to human serum albumin (HSA) increases the solid-state electronic conductance of a monolayer of the protein by >2 orders of magnitude for RA/HSA ≥ 3. Temperature-dependent ETp measurements show the following with increasing RA/HSA: (a) The temperature-independent current magnitude of the low-temperature (<190 K) regime increases significantly (>300-fold), suggesting a decrease in the distance-decay constant of the process. (b) The activation energy of the thermally activated regime (>190 K) decreases from 220 meV (RA/HSA = 0) to 70 meV (RA/HSA ≥ 3).
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