PLOS ONE: [sortOrder=DATE_NEWEST_FIRST, sort=Date, newest first, q=subject:"Chromatographic techniques"]PLOShttps://journals.plos.org/plosone/webmaster@plos.orgaccelerating the publication of peer-reviewed sciencehttps://journals.plos.org/plosone/search/feed/atom?sortOrder=DATE_NEWEST_FIRST&sort=Date,+newest+first&unformattedQuery=subject:%22Chromatographic+techniques%22All PLOS articles are Open Access.https://journals.plos.org/plosone/resource/img/favicon.icohttps://journals.plos.org/plosone/resource/img/favicon.ico2024-03-29T02:35:16ZA phage-displayed disulfide constrained peptide discovery platform yields novel human plasma protein bindersXinxin GaoHarini KaluarachchiYingnan ZhangSunhee HwangRami N. Hannoush10.1371/journal.pone.02998042024-03-28T14:00:00Z2024-03-28T14:00:00Z<p>by Xinxin Gao, Harini Kaluarachchi, Yingnan Zhang, Sunhee Hwang, Rami N. Hannoush</p>
Disulfide constrained peptides (DCPs) show great potential as templates for drug discovery. They are characterized by conserved cysteine residues that form intramolecular disulfide bonds. Taking advantage of phage display technology, we designed and generated twenty-six DCP phage libraries with enriched molecular diversity to enable the discovery of ligands against disease-causing proteins of interest. The libraries were designed based on five DCP scaffolds, namely <i>Momordica charantia</i> 1 (Mch1), gurmarin, Asteropsin-A, antimicrobial peptide-1 (AMP-1), and potato carboxypeptidase inhibitor (CPI). We also report optimized workflows for screening and producing synthetic and recombinant DCPs. Examples of novel DCP binders identified against various protein targets are presented, including human IgG Fc, serum albumin, vascular endothelial growth factor-A (VEGF-A) and platelet-derived growth factor (PDGF). We identified DCPs against human IgG Fc and serum albumin with sub-micromolar affinity from primary panning campaigns, providing alternative tools for potential half-life extension of peptides and small protein therapeutics. Overall, the molecular diversity of the DCP scaffolds included in the designed libraries, coupled with their distinct biochemical and biophysical properties, enables efficient and robust identification of <i>de novo</i> binders to drug targets of therapeutic relevance.Establishment of reference interval for hemoglobin A1C and other hemoglobin subfractions for healthy Saudi adultsAnwar BoraiKiyoshi IchiharaSuhad BahijriAbeer AlsofyaniMohieldin ElsayidHaitham HusainSultanah BoraieNaif SannanZiad KalantanMajdi JanMaha GassasMohammed HarbiNorah AlrowailiMohammed AlmohammadiHawazen ZarifMansour Qurashi10.1371/journal.pone.03000282024-03-25T14:00:00Z2024-03-25T14:00:00Z<p>by Anwar Borai, Kiyoshi Ichihara, Suhad Bahijri, Abeer Alsofyani, Mohieldin Elsayid, Haitham Husain, Sultanah Boraie, Naif Sannan, Ziad Kalantan, Majdi Jan, Maha Gassas, Mohammed Harbi, Norah Alrowaili, Mohammed Almohammadi, Hawazen Zarif, Mansour Qurashi</p>
Background <p>The establishment of Reference Intervals (RIs) for Hemoglobin A1C and other hemoglobin subfractions (A1A, A1B, F, LA1C, A0) is of utmost importance in screening, diagnosing, and monitoring diabetes and other hemoglobin abnormalities through the application of high-pressure liquid chromatography (HPLC) technique. Because there are no locally established RIs for these parameters, it is essential to establish RIs specific to the Saudi population to accurately diagnose and monitor diabetic individuals and identify abnormal levels in hemoglobin subfractions.</p> Methods <p>As part of the IFCC global multicenter study of laboratory reference values, a cross-sectional study was conducted in Saudi Arabia. The study involved recruiting a total of 381 healthy adult subjects (>18 years, BMI 28.3 ± 6 kg/m<sup>2</sup>). Blood samples were analyzed for A1C, biochemical and other immunoassay parameters. The need for RIs based on sex, age, and BMI was determined using the standard deviation ratio (SDR) through a 3-level nested ANOVA.</p> Results <p>Based on the threshold of SDR≥0.4, RIs for A1C and other Hb subfractions were not partitioned by sex or BMI, but partitioned by age (<45 & ≥45 years) for A1C, LA1C, A0 and F. Spearman’s correlation between glucose, insulin, and C-peptide showed a positive association with different hemoglobin subtractions of A1B, F, A1C, and LA1C. The RIs were obtained by using the parametric method and the latent abnormal values exclusion (LAVE) principle was applied on A1C.</p> Conclusion <p>This study established RIs for A1C and other Hb subfractions for healthy adult Saudis. Age was found to be an important source of variation for most of the parameters including A1C. These findings will enhance the understanding and clinical decision-making concerning A1C and other hemoglobin subfractions. The elevated upper limit of RIs for A1C reflects the high prevalence of diabetes in the Saudi population specially in those with increased age.</p>Structural and functional characterization of sulfurtransferase from <i>Frondihabitans</i> sp. PAMC28461Hackwon DoDieu Linh NguyenYong-Yoon AhnYewon NamYoonJi KangHoeJung OhJisub HwangSe Jong HanKitae KimJun Hyuck Lee10.1371/journal.pone.02989992024-03-25T14:00:00Z2024-03-25T14:00:00Z<p>by Hackwon Do, Dieu Linh Nguyen, Yong-Yoon Ahn, Yewon Nam, YoonJi Kang, HoeJung Oh, Jisub Hwang, Se Jong Han, Kitae Kim, Jun Hyuck Lee</p>
Sulfurtransferases transfer of sulfur atoms from thiols to acceptors like cyanide. They are categorized as thiosulfate sulfurtransferases (TSTs) and 3-mercaptopyruvate sulfurtransferases (MSTs). TSTs transfer sulfur from thiosulfate to cyanide, producing thiocyanate. MSTs transfer sulfur from 3-mercaptopyruvate to cyanide, yielding pyruvate and thiocyanate. The present study aimed to isolate and characterize the sulfurtransferase <i>Fr</i>ST from <i>Frondihabitans</i> sp. PAMC28461 using biochemical and structural analyses. <i>Fr</i>ST exists as a dimer and can be classified as a TST rather than an MST according to sequence-based clustering and enzyme activity. Furthermore, the discovery of activity over a wide temperature range and the broad substrate specificity exhibited by <i>Fr</i>ST suggest promising prospects for its utilization in industrial applications, such as the detoxification of cyanide.Rhinoceros beetle (<i>Trypoxylus dichotomus</i>) cuticular hydrocarbons contain information about body size and sexMicah A. BellGarrett LimChelsey CaldwellDouglas J. EmlenBrook O. Swanson10.1371/journal.pone.02997962024-03-14T14:00:00Z2024-03-14T14:00:00Z<p>by Micah A. Bell, Garrett Lim, Chelsey Caldwell, Douglas J. Emlen, Brook O. Swanson</p>
Japanese rhinoceros beetle (<i>Trypoxylus dichotomus</i>) males have exaggerated horns that are used to compete for territories. Larger males with larger horns tend to win these competitions, giving them access to females. Agonistic interactions include what appears to be assessment and often end without escalating to physical combat. However, it is unknown what information competitors use to assess each other. In many insect species chemical signals can carry a range of information, including social position, nutritional state, morphology, and sex. Specifically, cuticular hydrocarbons (CHCs), which are waxes excreted on the surface of insect exoskeletons, can communicate a variety of information. Here, we asked whether CHCs in rhinoceros beetles carry information about sex, body size, and condition that could be used by males during assessment behavior. Multivariate analysis of hydrocarbon composition revealed patterns associated with both sex and body size. We suggest that Rhinoceros beetles could be communicating information through CHCs that would explain behavioral decisions.The polyglutamine domain is the primary driver of seeding in huntingtin aggregationAdam SkeensChathuranga SiriwardhanaSophia E. MassinopleMichelle M. WunderZachary L. EllisKaitlyn M. KeithTyler GirmanShelli L. FreyJustin Legleiter10.1371/journal.pone.02983232024-03-14T14:00:00Z2024-03-14T14:00:00Z<p>by Adam Skeens, Chathuranga Siriwardhana, Sophia E. Massinople, Michelle M. Wunder, Zachary L. Ellis, Kaitlyn M. Keith, Tyler Girman, Shelli L. Frey, Justin Legleiter</p>
Huntington’s Disease (HD) is a fatal, neurodegenerative disease caused by aggregation of the huntingtin protein (htt) with an expanded polyglutamine (polyQ) domain into amyloid fibrils. Htt aggregation is modified by flanking sequences surrounding the polyQ domain as well as the binding of htt to lipid membranes. Upon fibrillization, htt fibrils are able to template the aggregation of monomers into fibrils in a phenomenon known as seeding, and this process appears to play a critical role in cell-to-cell spread of HD. Here, exposure of <i>C</i>. <i>elegans</i> expressing a nonpathogenic N-terminal htt fragment (15-repeat glutamine residues) to preformed htt-exon1 fibrils induced inclusion formation and resulted in decreased viability in a dose dependent manner, demonstrating that seeding can induce toxic aggregation of nonpathogenic forms of htt. To better understand this seeding process, the impact of flanking sequences adjacent to the polyQ stretch, polyQ length, and the presence of model lipid membranes on htt seeding was investigated. Htt seeding readily occurred across polyQ lengths and was independent of flanking sequence, suggesting that the structured polyQ domain within fibrils is the key contributor to the seeding phenomenon. However, the addition of lipid vesicles modified seeding efficiency in a manner suggesting that seeding primarily occurs in bulk solution and not at the membrane interface. In addition, fibrils formed in the presence of lipid membranes displayed similar seeding efficiencies. Collectively, this suggests that the polyQ domain that forms the amyloid fibril core is the main driver of seeding in htt aggregation.Structural insights into the modulation Of SOD1 aggregation By a fungal metabolite Phialomustin-B: Therapeutic potential in ALSSruthi UnniPadmini KommuSnehal AoutiYedukondalu NalliM. M. Srinivas BharathAsif AliBalasundaram Padmanabhan10.1371/journal.pone.02981962024-03-06T14:00:00Z2024-03-06T14:00:00Z<p>by Sruthi Unni, Padmini Kommu, Snehal Aouti, Yedukondalu Nalli, M. M. Srinivas Bharath, Asif Ali, Balasundaram Padmanabhan</p>
Amyotrophic lateral sclerosis (ALS) is a fatal human motor neuron disease leading to muscle atrophy and paralysis. Mutations in superoxide dismutase 1 (SOD1) are associated with familial ALS (fALS). The SOD1 mutants in ALS have a toxic-gain of function by destabilizing the functional SOD1 homodimer, consequently inducing fibril-like aggregation with a cytotoxic non-native trimer intermediate. Therefore, reducing SOD1 oligomerization <i>via</i> chemical modulators is an optimal therapy in ALS. Here, we report the discovery of Phialomustin-B, an unsaturated secondary metabolite from the endophytic fungus <i>Phialophora mustea</i>, as a modulator of SOD1 aggregation. The crystal structure of the SOD1-Phialomustin complex refined to 1.90 Å resolution demonstrated for the first time that the ligand binds to the dimer interface and the lateral region near the electrostatic loop. The aggregation analyses of SOD1<sup>WT</sup> and the disease mutant SOD1<sup>A4V</sup> revealed that Phialomustin-B reduces cytotoxic trimerization. We propose that Phialomustin-B is a potent lead molecule with therapeutic potential in fALS.Phenolic concentrations and carbon/nitrogen ratio in annual shoots of bilberry (<i>Vaccinium myrtillus</i>) after simulated herbivoryMarcel Schrijvers-GonlagChristina SkarpeRiitta Julkunen-TiittoAntonio B. S. Poléo10.1371/journal.pone.02982292024-03-04T14:00:00Z2024-03-04T14:00:00Z<p>by Marcel Schrijvers-Gonlag, Christina Skarpe, Riitta Julkunen-Tiitto, Antonio B. S. Poléo</p>
Herbivory can be reduced by the production of defense compounds (secondary metabolites), but generally defenses are costly, and growth is prioritized over defense. While defense compounds may deter herbivory, nutrients may promote it. In a field study in boreal forest in Norway, we investigated how simulated herbivory affected concentrations of phenolics (generally a defense) and the carbon/nitrogen (C/N) ratio in annual shoots of bilberry (<i>Vaccinium myrtillus</i>), a deciduous clonal dwarf shrub whose vegetative and generative parts provide forage for many boreal forest animals. We measured concentrations of total tannins, individual phenolics, nitrogen and carbon following several types and intensities of herbivory. We identified 22 phenolics: 15 flavonoids, 1 hydroquinone and 6 phenolic acids. After high levels of herbivory, the total tannin concentration and the concentration of these 22 phenolics together (called total phenolic concentration) were significantly lower in bilberry annual shoots than in the control (natural herbivory at low to intermediate levels). Low-intensive herbivory, including severe defoliation, gave no significantly different total tannin or total phenolic concentration compared with the control. Many individual phenolics followed this pattern, while phenolic acids (deterring insect herbivory) showed little response to the treatments: their concentrations were maintained after both low-intensive and severe herbivory. Contrary to our predictions, we found no significant difference in C/N ratio between treatments. Neither the Carbon:Nutrient Balance hypothesis nor the Optimal Defense hypotheses, theories predicting plant resource allocation to secondary compounds, can be used to predict changes in phenolic concentrations (including total tannin concentration) in bilberry annual shoots after herbivory: in this situation, carbon is primarily used for other functions (e.g., maintenance, growth, reproduction) than defense.Impact of pesticides exposure on <i>Archachatina marginata</i> snails in four Cameroon monomodal rainforest sitesAnnick Niquaise Enangue NjembeleMaeva Arielle Patience Seppo NjembeleEmmanuel Henoch Dicka kwambeAlexis Hamdja NgoniriSylvie Ntyam epse OndoKingsley Agbor Etchu10.1371/journal.pone.02973692024-03-04T14:00:00Z2024-03-04T14:00:00Z<p>by Annick Niquaise Enangue Njembele, Maeva Arielle Patience Seppo Njembele, Emmanuel Henoch Dicka kwambe, Alexis Hamdja Ngoniri, Sylvie Ntyam epse Ondo, Kingsley Agbor Etchu</p>
Cameroon monomodal rainforest zone has a strong agricultural activity and is therefore exposed to pesticides. Furthermore, the area possesses climatic factors that favor the growth of <i>Achatinadea</i> snails known as African giant snails, a delicacy for the local population. The present study aimed to evaluate pesticides contamination (less vs more exposed areas) through assessment of exposure and impact on <i>Achatinadea</i> snails. <i>Achatinadea</i> snails were collected within intensive agricultural areas (Njombe and Kribi rural) and in areas with less agricultural activity (Ebodje and Dibombari). Collection was performed at night between July and September 2020 using an adapted square kilometer method. Type, number, weight, and size of the collected snails were analyzed and compared using Welsh’s One-way Analysis of variance (ANOVA). After removing the soft part from the shell, the presence of pesticides was determined using mass spectrometry. Histological analysis of kidney and ovo-testis was performed using eosin-hematoxylin staining. Results showed that the main variety of snails collected are <i>Archachatina marginata</i>. In areas with less agricultural activity, snails are bigger than those from more agricultural areas heavily using pesticides. Furthermore, pesticides detection showed that glyphosate, but not metalaxyl, is present in animals coming from all the collection sites. Cypermethrin was found in all the samples except in those from Dibombari. Histology revealed that the structure of the kidney and ovo-testis of snails from more exposed areas is impaired. In conclusion, this study revealed that some pesticides are transferred to snail and impair the structure of important organs.Chemo-profiling of <i>Purpureocillium lilacinum</i> and <i>Paecilomyces variotii</i> isolates using GC-MS analysis, and evaluation of their metabolites against <i>M</i>. <i>incognita</i>Prashant PatidarLakshman PrasadSushma SagarAnil SirohiMahender Singh SaharanMukesh Kumar DhillonVaibhav Kumar SinghTusar Kanti Bag10.1371/journal.pone.02979252024-02-15T14:00:00Z2024-02-15T14:00:00Z<p>by Prashant Patidar, Lakshman Prasad, Sushma Sagar, Anil Sirohi, Mahender Singh Saharan, Mukesh Kumar Dhillon, Vaibhav Kumar Singh, Tusar Kanti Bag</p>
Nematophagous fungi are the best alternatives to chemical nematicides for managing nematodes considering environmental health. In the current study, activity of metabolites from ten isolates of <i>Purpureocillium lilacinum</i> (Thom) Luangsa-ard (<i>Hypocreales</i>: <i>Ophiocordycipitaceae</i>) and two isolates of <i>Paecilomyces variotii</i> Bainier (<i>Eurotiales</i>: <i>Trichocomaceae</i>), were examined to inhibit the hatching of <i>Meloidogyne incognita</i> (Kofoid & White) Chitwood (<i>Tylenchida</i>: <i>Heteroderidae</i>) eggs. At 100%, 50%, and 25% concentrations, respectively, the culture filtrate of the isolate <i>P</i>. <i>lilacinum</i> 6887 prevented 97.55%, 90.52%, and 62.97% of egg hatching. Out of all the isolates, Pl 6887, Pl 6553, and Pl 2362 showed the greatest results in the hatching inhibition experiment.Gas chromatography-mass spectrometry (GC-MS) analysis revealed a variety of nematicidal compounds from different isolates. A total of seven nematicidal compounds, including four very potent nematicidal fatty acids were found in the isolate Pl 6553. Secondary metabolites of the same isolate possess the highest <i>M</i>. <i>incognita</i> juvenile mortality, i.e., 43.33% and 92% after 48 hrs of treatment at 100 and 200 ppm concentrations, respectively. Significant difference was observed in juvenile mortality percentage among the isolate having highest and lowest nematicidal compounds. Nematicidal fatty acids like myristic and lauric acid were found for the first time in <i>P</i>. <i>lilacinum</i>. Multiple vacuole-like droplets were found inside the unhatched eggs inoculated with the culture filtrate of isolate Pl 6887, and also in the juveniles that perished in the ethyl acetate extract of isolate Pl 6553.Biochemical characterization of bioinspired nanosuspensions from <i>Swertia chirayita</i> extract and their therapeutic effects through nanotechnology approachAyesha RazaTayyab AliMuhammad NaeemMuhammad AsimFatma HussainZhiye LiAbdul Nasir10.1371/journal.pone.02931162024-02-08T14:00:00Z2024-02-08T14:00:00Z<p>by Ayesha Raza, Tayyab Ali, Muhammad Naeem, Muhammad Asim, Fatma Hussain, Zhiye Li, Abdul Nasir</p>
<i>Swertia chirayita</i> is used as a traditional medicinal plant due to its pharmacological activities, including antioxidant, antidiabetic, antimicrobial, and cytotoxic. This study was aimed to evaluate the therapeutic efficacy of newly synthesized nanosuspensions from <i>Swertia chirayita</i> through nanotechnology for enhanced bioactivities. Biochemical characterization was carried out through spectroscopic analyses of HPLC and FTIR. Results revealed that extract contained higher TPCs (569.6 ± 7.8 mg GAE/100 g)) and TFCs (368.5 ± 9.39 mg CE/100 g) than <i>S. chirayita</i> nanosuspension, TPCs (500.6 ± 7.8 500.6 ± 7.8 mg GAE/100 g) and TFCs (229.5± 3.85 mg CE/100 g). Antioxidant activity was evaluated through DPPH scavenging assay, and nanosuspension exhibited a lower DPPH free radical scavenging potential (06 ±3.61) than extract (28.9± 3.85). Anti-dabetic potential was assessed throughα-amylase inhibition and anti-glycation assays. Extract showed higher (41.4%) antiglycation potential than 35.85% nanosuspension and 19.5% α-amylase inhibitory potential than 5% nanosuspension. Biofilm inhibition activity against <i>E. coli</i> was higher in nanosuspension (69.12%) than extract (62.08%). The extract showed high cytotoxicity potential (51.86%) than nanosuspension (33.63%). These nanosuspensions possessed enhanced bioactivities for therapeutic applications could be explored further for the development of new drugs.SRPK2 Mediates HBV Core Protein Phosphorylation and Capsid Assembly via Docking InteractionRyan Pak Hong YIPDoris Ching Ying KwokLouis Tung Faat LaiSiu-Ming HoIvan Chun Kit WongChi-Ping ChanWilson Chun Yu LauJacky Chi Ki Ngo10.1371/journal.ppat.10119782024-02-07T14:00:00Z2024-02-07T14:00:00Z<p>by Ryan Pak Hong YIP, Doris Ching Ying Kwok, Louis Tung Faat Lai, Siu-Ming Ho, Ivan Chun Kit Wong, Chi-Ping Chan, Wilson Chun Yu Lau, Jacky Chi Ki Ngo</p>
Members of the serine–arginine protein kinase (SRPK) family, SRPK1 and SRPK2, phosphorylate the hepatitis B core protein (Cp) and are crucial for pregenomic RNA encapsidation during viral nucleocapsid assembly. Among them, SRPK2 exhibits higher kinase activity toward Cp. In this study, we identified Cp sites that are phosphorylated by SRPK2 and demonstrated that the kinase utilizes an SRPK-specific docking groove to interact with and regulate the phosphorylation of the C-terminal arginine rich domain of Cp. We determined that direct interaction between the docking groove of SRPK2 and unphosphorylated Cp inhibited premature viral capsid assembly <i>in vitro</i>, whereas the phosphorylation of the viral protein reactivated the process. Pull-down assays together with the new cryo-electron microscopy structure of the HBV capsid in complex with SRPK2 revealed that the kinases decorate the surface of the viral capsid by interacting with the C-terminal domain of Cp, underscoring the importance of the docking interaction in regulating capsid assembly and pregenome packaging. Moreover, SRPK2-knockout in HepG2 cells suppressed Cp phosphorylation, indicating that SRPK2 is an important cellular kinase for HBV life cycle.Impact of interstitial lung disease on left ventricular myocardial functionMax Jonathan StumpfMarina Michaela Luise WirtzMax Fabian FleddermannLeonie BienerLeonie WeinholdMarcel WeberChristian Alexander SchaeferGeorg NickenigDirk SkowaschCarmen Pizarro10.1371/journal.pone.02864232024-02-06T14:00:00Z2024-02-06T14:00:00Z<p>by Max Jonathan Stumpf, Marina Michaela Luise Wirtz, Max Fabian Fleddermann, Leonie Biener, Leonie Weinhold, Marcel Weber, Christian Alexander Schaefer, Georg Nickenig, Dirk Skowasch, Carmen Pizarro</p>
Background <p>Interstitial lung disease (ILD) comprises a wide variety of pulmonary parenchymal disorders within which progressive fibrosing ILD (PF-ILD) constitutes a phenotypic subset. By use of speckle tracking-based strain analysis we aimed to evaluate the degree of left ventricular (LV) dysfunction in progressive vs. non-progressive fibrosing ILD (non-PF-ILD).</p> Methods <p>A total of 99 ILD patients (mean age 63.7 ± 13.5 years, 37.4% female), composed of 50 PF-ILD and 49 non-PF-ILD patients, and 33 controls were prospectively enrolled and underwent conventional and speckle tracking echocardiography. Additional laboratory and pulmonary function testing, as well as six-minute walk test were performed.</p> Results <p>As compared to the non-PF-ILD cohort, PF-ILD patients exhibited a significantly impaired forced vital capacity (2.4 ± 1.0l vs. 3.1 ± 0.9l, p = 0.002), diffusion capacity for carbon monoxide (DL<sub>CO</sub>, 25.6 ± 16.3% predicted vs. 43.6 ± 16.67% predicted, p <0.001) and exercise capacity response as measured by the six-minute walk test distance (268.1 ± 178.2m vs. 432.6 ± 94.2m, p <0.001). Contrary to conventional echocardiographic LV parameters, both regional and global longitudinal LV strain measurements were significantly altered in ILD patients as compared to controls. No differences in LV strain were found between both patient groups. Significant correlations were observed between global longitudinal strain, on the one hand, and systemic inflammation markers, total lung capacity (TLC) and DL<sub>CO</sub>, on the other hand (high-sensitivity C-reactive protein: Pearson´s r = -0.30, p< 0.001; interleukin-6: Pearson´s r = -0.26, p = 0.007; TLC % predicted: Pearson´s r = 0.22, p = 0.02; DL<sub>CO</sub> % predicted: Pearson´s r = 0.21, p = 0.02).</p> Conclusions <p>ILD is accompanied by LV dysfunction. LV functionality inversely correlates with the severity of the restrictive ventilatory defect and inflammation marker levels. These observations support the assumption of persistent low-grade systemic inflammation that may link systemic cardiovascular function to ILD status.</p>Impact of post-COVID-19 lung damage on pulmonary function, exercise tolerance and quality of life in Indian subjectsDevasahayam Jesudas ChristopherBarney T. J. IsaacFlavita Benna JohnDeepa ShankarPrasanna SamuelRicha GuptaBalamugesh Thangakunam10.1371/journal.pgph.00028842024-02-01T14:00:00Z2024-02-01T14:00:00Z<p>by Devasahayam Jesudas Christopher, Barney T. J. Isaac, Flavita Benna John, Deepa Shankar, Prasanna Samuel, Richa Gupta, Balamugesh Thangakunam</p>
After recovery from COVID-19, there is data to suggest potential long-term pulmonary sequelae and associated impairment of functional capacity. This cross-sectional study was designed to assess the impact on respiratory function in a cohort of Indian subjects. Subjects who had recovered from COVID-19 were recruited. Clinical symptoms, pulmonary function test results, 6-minute walk test (6MWT) results, St George’s Respiratory questionnaire (SGRQ) and chest radiographs were obtained. Information on the COVID-19 illness during hospitalization, baseline laboratory biomarkers and the disease severity categories as outlined by WHO (asymptomatic, mild, moderate, severe and critical), were retrieved from the hospital records. The ‘COVID pneumonia’(WHO category moderate, severe & critical) group was compared with the ‘Mild COVID’ (WHO category mild) group and likewise, the WHO category moderate and the WHO category severe/critical groups were compared. In 207 subjects, whose mean age was 48.7 years were assessed after an average of 63 days from onset of symptom, 35% had TLC< 80% (restrictive defect), 8.3% had FEV1/FVC<70% (obstructive defect) and 44.4% had diminished DLCO<80% (diffusing capacity). The ‘COVID-19 pneumonia’ group when compared to the ‘mild COVID-19’ group, had lower FVC% (77.85 VS 88.18; P = 0.001), TLC% (79.48 VS 87.91; P = 0.0002), DLCO% (75.30 VS 89.20; P<0.0001) and DLCO/VA% (105.6 VS 111.8; P = 0.032), decreased minimum oxygen saturation (94.89 VS 97.73; P<0.0001) and more subjects had a drop in saturation of ≥ 4% (21.69% VS 4.84%; P = 0.001) during the 6MWT, and a greater mean total SGRQ score (29.2 VS 11.0; P<0.0001). To our knowledge, this is the first such report on Indian subjects. We have shown that post-COVID-19 lung damage leads to significant impairment of lung function, quality of life and effort tolerance.Development and evaluation of a computerized algorithm for the interpretation of pulmonary function testsYuh-Chin T. HuangLuke HenriquezHengji ChenCraig Henriquez10.1371/journal.pone.02975192024-01-29T14:00:00Z2024-01-29T14:00:00Z<p>by Yuh-Chin T. Huang, Luke Henriquez, Hengji Chen, Craig Henriquez</p>
Pulmonary function tests (PFTs) are usually interpreted by clinicians using rule-based strategies and pattern recognition. The interpretation, however, has variabilities due to patient and interpreter errors. Most PFTs have recognizable patterns that can be categorized into specific physiological defects. In this study, we developed a computerized algorithm using the python package (pdfplumber) and validated against clinicians’ interpretation. We downloaded PFT reports in the electronic medical record system that were in PDF format. We digitized the flow volume loop (FVL) and extracted numeric values from the reports. The algorithm used FEV1/FVC<0.7 for obstruction, TLC<80%pred for restriction and <80% or >120%pred for abnormal DLCO. The algorithm also used a small airway disease index (SADI) to quantify late expiratory flattening of the FVL to assess small airway dysfunction. We devised keywords for the python Natural Language Processing (NLP) package (spaCy) to identify obstruction, restriction, abnormal DLCO and small airway dysfunction in the reports. The algorithm was compared to clinicians’ interpretation in 6,889 PFTs done between March 1<sup>st</sup>, 2018, and September 30<sup>th</sup>, 2020. The agreement rates (Cohen’s kappa) for obstruction, restriction and abnormal DLCO were 94.4% (0.868), 99.0% (0.979) and 87.9% (0.750) respectively. In 4,711 PFTs with FEV1/FVC≥0.7, the algorithm identified 190 tests with SADI < lower limit of normal (LLN), suggesting small airway dysfunction. Of these, the clinicians (67.9%) also flagged 129 tests. When SADI was ≥ LLN, no clinician’s reports indicated small airway dysfunction. Our results showed the computerized algorithm agreed with clinicians’ interpretation in approximately 90% of the tests and provided a sensitive objective measure for assessing small airway dysfunction. The algorithm can improve efficiency and consistency and decrease human errors in PFT interpretation. The computerized algorithm works directly on PFT reports in PDF format and can be adapted to incorporate a different interpretation strategy and platform.Src-NADH dehydrogenase subunit 2 complex and recognition memory of imprinting in domestic chicksLela ChitadzeMaia MeparishviliVincenzo LaganiZaza KhuchuaBrian J. McCabeRevaz Solomonia10.1371/journal.pone.02971662024-01-29T14:00:00Z2024-01-29T14:00:00Z<p>by Lela Chitadze, Maia Meparishvili, Vincenzo Lagani, Zaza Khuchua, Brian J. McCabe, Revaz Solomonia</p>
Src is a non-receptor tyrosine kinase participating in a range of neuronal processes, including synaptic plasticity. We have recently shown that the amounts of total Src and its two phosphorylated forms, at tyrosine-416 (activated) and tyrosine-527 (inhibited), undergoes time-dependent, region-specific learning-related changes in the domestic chick forebrain after visual imprinting. These changes occur in the intermediate medial mesopallium (IMM), a site of memory formation for visual imprinting, but not the posterior pole of the nidopallium (PPN), a control brain region not involved in imprinting. Src interacts with mitochondrial genome-coded NADH dehydrogenase subunit 2 (NADH2), a component of mitochondrial respiratory complex I. This interaction occurs at brain excitatory synapses bearing NMDA glutamate receptors. The involvement of Src-NADH2 complexes in learning and memory is not yet explored. We show for the first time that, independently of changes in total Src or total NADH2, NADH2 bound to Src immunoprecipitated from the P2 plasma membrane-mitochondrial fraction: (i) is increased in a learning-related manner in the left IMM 1 h after the end of training; (ii), is decreased in the right IMM in a learning-related way 24 h after training. These changes occurred in the IMM but not the PPN. They are attributable to learning occurring during training rather than a predisposition to learn. Learning-related changes in Src-bound NADH2 are thus time- and region-dependent.